ʻIke aku, ʻike mai, kōkua aku kōkua mai; pēlā ihola ka nohona ʻohana.

Recognize and be recognized, help and be helped; such is family life.

[Family life requires an exchange of mutual help and recognition.]

‘Ōlelo No‘eau, compiled by Mary Kawena Pukui, #1200

Introduction

Figure 3.1 (a) a human cell with organelles. (By OpenStax — https://cnx.org/contents/FPtK1zmh@8.25:fEI3C8Ot@10/Preface, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=30131195) (b) A campus map of UH Manoa.

3.1 Overview of a General Human Cell

In the previous chapter, you learned about the structures and functions of atoms, water, proteins, and other molecules on a chemical level. All of these molecules are the building blocks of a human cell — the basic unit of life (Figure 3.1a). Each of us has an average of 100 trillion cells, and our cells are composed of the following three main parts: cell membrane, cytoplasm, and nucleus. In this chapter, we will start a new journey on learning about the structures and functions of cells. To help you visualize the different parts and roles of the cells, we will use “your college” and its functional components as an analogy throughout this chapter (Figure 3.1b). For example, you and your classmates are the building blocks of the college (e.g., proteins of a cell), and your department is similar to an organelle. The boundary of the campus is the cell membrane, the campus area is the cytoplasm, and the administration team is the nucleus.

Cell Membrane

Imagine that your friend is asking where you are, and you tell them that you are either on-campus or off-campus. The boundaries and borders of the campus indicate whether you are inside or outside the campus. The border of your campus is similar to the cell membrane (plasma membrane). Just as the border of your campus separates on-campus and off-campus, the cell membrane separates the inner contents of your cell from its exterior environment. A cell membrane provides a protective barrier around the cell. The space and fluids outside the cells are called extracellular space and extracellular fluids (ECF), respectively. On the other hand, the space and fluids inside the cells are called intracellular space and intracellular fluids (ICF), respectively. The cell membrane also plays a role in regulating which materials can enter or exit.

Cytoplasm

Once you are on campus, you can see the campus grounds and buildings with various departments. Similarly, once you enter a cell, you will see the cytosol and organelles. The cytoplasm (cyto (cell), plasm (fluid)) consists of all the contents and space between the cell membrane and the nucleus. Cytosol is a jelly-like substance within the cell and provides the fluid medium necessary for biochemical reactions. An organelle (little organ) refers to smaller structures within the cell that each performs a unique function or job, just as the various departments at your college work together to perform the overall duties of a campus.

Nucleus

The nucleus is generally considered the control center of the cell because it stores most of the deoxyribonucleic acid (DNA) in your cells. The DNA in your nucleus contains the genetic instructions for manufacturing proteins. In this analogy, the nucleus would be the administrative team or building on campus that makes the overall decisions that affect the organelles (just as a college president’s decisions affect departments), and the cell as a whole (just as administrative decisions affect an entire campus).

3.2 Cell Membrane

Just as your college campus has fences, walls, or streets that mark the campus boundary, the cell membrane is the boundary of a cell. The cell membrane provides a protective barrier around the cell, regulates which materials can pass in or out, and maintains differences in the contents between the inside of a cell and its exterior environment. This ability to regulate the flow of materials in and out of your cell is similar to the way delivery services and campus security guards can control what goes into and out of your campus.

Structure of a Cell Membrane

The cell membrane primarily consists of phospholipids and proteins. Phospholipids are a type of lipid molecule which are the main component of the cell membrane. The cell membrane is arranged in a phospholipid bilayer, meaning that the membrane is made out of two layers of phospholipids.

Phospholipids and Phospholipid Bilayer

In the chemistry chapter, we learned that a single phospholipid molecule is amphipathic because it has both hydrophilic (hydro (water) and philic (loving)) and hydrophobic (hydro (water) and phobic (fearing)) parts in its chemical structure. The hydrophilic head contains a phosphate group that is negatively charged, which makes the head attracted to water. The hydrophobic tails are made of two fatty acid chains (Figure 3.2) that do not have a strong attraction to water.

Figure 3.2 Phospholipid Structure A phospholipid molecule consists of a polar phosphate “head,” which is hydrophilic and a nonpolar lipid “tail,” which is hydrophobic. Unsaturated fatty acids result in kinks in the hydrophobic tails.

The cell membrane contains two layers of phospholipids, which is called a phospholipid bilayer (bi (two)). The hydrophilic heads of the phospholipids are arranged so that the heads of one layer face toward the intracellular fluid (ICF) inside of the cell, and the heads of the other layer faces toward the extracellular fluid (ECF) outside of the cell (Figure 3.3). This happens because the hydrophilic head of the phospholipid is attracted to the water in those fluids. The hydrophobic tails of the phospholipid face the tails of the phospholipid in the other layer, which forms a hydrophobic region between the two layers of phospholipids. This hydrophobic inner region of the cell membrane prevents water from intracellular and extracellular fluid from accumulating in the space between the phospholipid layers.

The amphipathic properties of phospholipids are also the basis of how soap works. The soap contains chemicals called detergents, which are also amphipathic. The hydrophobic portions of detergents can mix in with oils and lipids to help break up oily and greasy substances, while the hydrophilic portions can dissolve in water, which is why the mixture of soap and oils can be washed away with water. The ability of detergents to dissolve oils and mix with water is also why washing your hands with soap and water is effective in reducing your chance of infection from bacteria and viruses. The detergents in hand soap can dissolve bacterial and viral membranes, which can break apart their structure and destroy them.

Figure 3.3 Phospholipid Bilayer The phospholipid bilayer consists of two adjacent sheets of phospholipids, arranged tail to tail. The hydrophobic tails associate with one another, forming the interior of the membrane. The polar heads contact the fluid inside and outside of the cell.

Other molecules, such as other lipids (e.g., cholesterol) and proteins, may be embedded within the phospholipid bilayer or attached to the surfaces of the cell membrane. An important feature of the membrane is that it remains fluid; the lipids and proteins in the cell membrane are not rigidly locked in place, which allows molecules and proteins in the cell membrane freedom to move across the membrane to where they are needed.

Membrane Proteins: Integral Proteins, Peripheral Proteins, and Glycoproteins

Imagine that phospholipids are like bricks that make up a wall at the campus boundary. Imagine that the campus wall is more than just a simple brick wall, but also may contain gates, mailboxes, doorbells, and intercoms. Similarly, the cell membrane is more than just a simple phospholipid bilayer and is peppered throughout its surface with various proteins and other molecules (Figure 3.4).

Figure 3.4 Cell Membrane The cell membrane of the cell is a phospholipid bilayer containing many different molecular components, including proteins and cholesterol, some with carbohydrate groups attached.

As its name suggests, an integral protein is a protein that is embedded and integrated into the cell membrane. Integral proteins span the width of the cell membrane and are thus exposed to both the extracellular environment and the cytoplasm inside the cell. An example of integral proteins are ion channel which forms a bridge between the extracellular fluid and the cytoplasm and allows ions to move across the plasma membrane. Integral proteins can also be used as receptors to recognize each other or other molecules and communicate with another cell. Some integral proteins can also serve dual roles as both a membrane receptor and an ion channel. An example of this are membrane receptors for neurotransmitters, which can be found on nerve cells. When these membrane receptors bind neurotransmitters, such as dopamine, it causes the same protein to open up as an ion channel.

Glycoproteins (glyco (sugar)) are another category of integral membrane proteins and are named as such because they consist of carbohydrate molecules attached to a protein. The carbohydrates of a glycoprotein face outward toward the extracellular environment and acts as a tag to aid in cell recognition. In our campus analogy, these glycoproteins would be similar to the signs that greet you on campus and identify what college you are visiting. For example, your A/B/O blood type is determined by the type of carbohydrates attached to glycoproteins on your red blood cells. This type of cell identification and recognition through glucoproteins is important in blood transfusions. If a donor’s blood type doesn’t match with the recipient’s blood type during transfusion, the immune system of the recipient does not recognize the donor’s red blood cells as belonging there, which causes the recipient’s immune system to attack the red blood cells and cause a potentially life-threatening transfusion reaction.

Peripheral proteins are typically found on the inner or outer surface of the cell membrane but do not span the width of the membrane. For example, peripheral proteins on the surface of your intestinal cells act as digestive enzymes to break down nutrients from food into smaller molecules that can pass through cells lining your intestines and into your bloodstream.

Membrane Transport

Selective Permeability

The ECF surrounding your cells and the cytosol inside your cells have very different compositions and concentrations of ions and molecules. An important job of the cell membrane is to maintain these different concentrations between the ECF and ICF. For example, sodium ions are maintained at much higher concentrations in the ECF than in ICF. This sodium concentration balance is essential for nerve and muscle cells to function properly. The difference in a molecule or ion’s concentration between the ECF and ICF is often referred to as that substance’s concentration gradient.

The cell membrane has selective permeability, meaning that it only allows certain, but not all, substances and molecules to freely cross the membrane. The hydrophobic interior in the cell membrane slows or impedes the movement of certain molecules through the membrane, especially hydrophilic molecules. The tight arrangement of the phospholipid bilayer also prevents the movement of larger molecules through the cell membrane. This is why the cell membrane is described as selectively permeable or semi-permeable. Selectively permeable also stands in contrast to freely permeable, which would be a membrane that allows all substances to cross its boundaries, or impermeable, which would be a membrane that does not allow any substance to cross.

Generally, only relatively small, hydrophobic or nonpolar materials can freely cross through the phospholipid bilayer because the phospholipid tails are hydrophobic. Examples of molecules that can freely cross the phospholipid tail barrier are lipids, lipid-soluble hormones, oxygen and carbon dioxide gases, and alcohols. However, water-soluble materials — as with glucose, amino acids, electrolytes, and water-soluble hormones — cannot cross the membrane because they are repelled by the hydrophobic interior of the bilayer. Therefore water-soluble substances need some help or additional energy to move across the cell membrane.

Cultural Connection

Loko i’a — Fishponds

Figure 3.5 Loko Iʻa

Hana a lau a lau ke aho, a laila loaʻa ka iʻa kāpapa o ka moana.

Make four hundred times four hundred fish lines before planning to go after the fighting fish of the sea.

Loko iʻa, fishponds, play an integral part in Hawaiian society and support an ecosystem made of a diverse collection of aquatic plants and animals for food. The fishpond rock wall operates similar to a cell membrane — its structure supports the operations of the cell by being selectively permeable. Some fishponds are called loko kuapā and feature a distinctive rock wall interspersed with mākāhā (wooden sluice gates), designed to capture and attract juvenile ʻamaʻama (mullet), awa (milkfish), and shellfish. Because fishponds are built where freshwater meets the ocean either at a river mouth or where freshwater comes off the land or from underground springs, the water in the fishpond is brackish (a mixture of fresh and seawater). The freshwater percolating through the ground or flowing from streams brings minerals to the pond and acts as fertilizer for algae and phytoplankton, creating a nutrient-filled environment for the fish to thrive. Along with the smaller-sized juvenile fish crossing the fishpond’s rock-wall boundary, water moves in and out of the fishpond with the tide. Once the juvenile fish mature, they become too large to leave the fishpond, and the higher concentration of large fish provides a rich food source for the people. Learn more about the loko iʻa at this webpage.

Passive Processes

Diffusion

Passive transport is the movement of substances without requiring the help of cellular energy. To understand how substances can move passively across a cell membrane, it is necessary to understand concentration gradients and diffusion. A concentration gradient is a difference in the concentration of a substance across space. Molecules or ions will spread from where they are more concentrated (“higher” concentration) to where they are less concentrated (“lower” concentration) until they are equally distributed in that space. This process is called diffusion. When molecules move in this way from a higher to lower concentration, they are said to move ”down” their concentration gradient and no energy is required. Imagine baking chocolate chip cookies in the oven. As the cookies bake, the smell of the cookies would naturally diffuse from the oven to the living room and the rest of the rooms in your house. This diffusion would go on until the sweet scent is equally distributed or when no more concentration gradient remains. This diffusion is also a passive process because it can occur without you needing to spend energy to waft and move the scent molecules yourself.

Diffusion also is affected and sped up by temperature and heat. In our cookie example, if the room is warmer, diffusion occurs even faster as the molecules have more energy from the heat and they are bumping into each other and spreading out faster than at cooler temperatures. The human body typically has an internal temperature of around (98.6°F, 37°C) which also aids in the diffusion of particles within the body.

If a substance can move across the cell membrane and it has a concentration gradient across the membrane, diffusion will occur (Figure 3.6). For example, oxygen (O2) and carbon dioxide (CO2) gases can easily diffuse through the lipid bilayer of the cell membrane due to their small particle size and nonpolar nature. As substances move down their concentration gradient O2 generally diffuses into cells because cells constantly use up oxygen as they generate the ATP needed for their metabolism and to stay alive. This constant consumption of O2 is why cells typically have a lower concentration of O2 in the cytoplasm than the outside extracellular fluid. On the other hand, CO2 typically diffuses out of cells because cells produce CO2 as a byproduct of metabolism, resulting in a higher concentration of CO2 inside a cell than the CO2 concentration in the extracellular fluid. Neither O2 diffusion into a cell nor CO2 diffusion out of a cell requires any energy on the part of the cell, making both examples of diffusion and passive transport.

Figure 3.6 Diffusion across the Cell (Plasma) Membrane The structure of the lipid bilayer allows small, uncharged substances such as oxygen and carbon dioxide, and hydrophobic molecules such as lipids, to pass through the cell membrane, down their concentration gradient, by diffusion.

Facilitated Diffusion

Charged molecules, such as ions, and large hydrophilic molecules cannot diffuse across the cell membrane by themselves and are repelled by the hydrophobic tails of the phospholipid bilayer. As a result, ions, such as sodium ions (Na+), and many hydrophilic molecules, such as glucose, need help in crossing the cell membrane. Facilitated diffusion is a special type of diffusion that can transport substances that cannot readily cross the lipid bilayer due to their size, charge, and/or polarity (Figure 3.7). Glucose is an example of a molecule that can be transported into the cell by facilitated diffusion. Even if glucose has a concentration gradient where glucose is more concentrated on the outside of a cell, glucose cannot enter the cell via simple diffusion because it is both large and polar, thus preventing it from crossing the lipid bilayer. Cells may place specialized carrier proteins called glucose transporters at their surface to allow glucose to move into their cytoplasm. Glucose transporters are proteins that act like little doorways in the cell membrane that only allow glucose to pass through the plasma membrane and facilitate the movement of glucose into the cell, hence facilitating diffusion.

Figure 3.7 Facilitated Diffusion (a) Facilitated diffusion of substances crossing the cell (plasma) membrane takes place with the help of proteins such as channel proteins and carrier proteins. Channel proteins are less selective than carrier proteins, and usually, mildly discriminate between their cargo based on size and charge. (b) Carrier proteins are more selective, often only allowing one particular type of molecule to cross.

Another example of facilitated diffusion is the transport of sodium ions (Na+) using channel proteins. Even though sodium ions are highly concentrated outside of cells, their electric charge prevents them from passing through the nonpolar lipid bilayer of the membrane. Sodium channels open up passages in the cell membrane that facilitate the diffusion of Na+ down the sodium concentration gradient and allow Na+ to diffuse from the ECF surrounding cells to the inside of a cell. Sodium channels are also very specific and selective in that they only allow sodium ions to pass through. Other ions, such as potassium ions (K+) and chloride ions (Cl-) have bigger atomic sizes or different charges, and cannot pass through sodium channels.

Both diffusion and facilitated diffusion are methods of passive transport. “Simple diffusion” is sometimes used to compare diffusion that occurs with molecules that can freely cross the cell membrane, versus molecules that require facilitated diffusion through the carrier or channel proteins. As a form of passive transport, facilitated diffusion does not require cellular energy and still obeys the rules of diffusion. In both the glucose and sodium ion examples mentioned in this section, facilitated diffusion still follows the concentration gradient of each substance, and only moves substances from a higher concentration to a lower concentration without using any additional energy input from the cell.

Osmosis

Water can move freely across the cell membrane of all cells and can be transported across a cell membrane through protein channels or by diffusion. Even though water is a polar molecule, it is a relatively tiny molecule compared to the phospholipids and other molecules in the cell membrane. The small size of a water molecule allows water to diffuse across the cell membrane by slipping and squeezing between the lipid tails of the phospholipid bilayer.

Water can also diffuse across a concentration gradient. If there is an imbalance or concentration gradient of solutes between two sides of a semipermeable membrane, the laws of nature and thermodynamics try to spread out molecules and even out the concentrations between the two sides of a membrane. If solutes can not pass through a membrane, then water molecules will diffuse and move down their concentration gradient to try and balance out the solute concentrations on both sides of the membrane. This process of water diffusing through a semipermeable membrane to create a balance between the two solutions is called osmosis (Figure 3.8). In osmosis, water will diffuse and move from a solution that has more water (thus a lower solute concentration) to a solution that has less water and a higher solute concentration. The overall movement of water to the solution with less water will dilute the solution’s high solute concentration, thus lowering the solute concentration and bringing the solute concentrations of the two solutions closer together.

Figure 3.8 Osmosis Osmosis is the diffusion of water through a semipermeable membrane down its concentration gradient. If a membrane is permeable to water, though not to a solute, water will equalize its own concentration by diffusing to the side of lower water concentration (and thus the side of higher solute concentration). In the beaker on the left, the solution on the right side of the membrane is hypertonic.

The relative solute concentrations between two solutions is referred to as tonicity. Two solutions that have the same concentration of solutes are said to be isotonic (iso (same), tonic (tension)) to each other . When the ICF inside the cell and ECF outside the cell are isotonic, water will still diffuse and travel in and out of the cell, but there will be no net movement of water molecules across the cell membrane, meaning that the cell will neither gain nor lose water. Therefore, a cell that is in isotonic conditions relative to its ECF will maintain its normal shape, volume, and function since it is maintaining its overall concentration of water molecules (Figure 3.9a).

A solution that has a lower concentration of solutes than another solution is said to be hypotonic (hypo (under)). Water molecules tend to diffuse out of a hypotonic solution since a hypotonic solution would have a relatively high water concentration and a low solute concentration. For example, red blood cells immersed in a hypotonic solution will have an overall movement of water into the cells via osmosis. This increased movement of water into cells can cause them to take on too much water and swell, with the risk of eventually bursting due to cells taking on too much volume and pressure, much like an overinflated balloon (Figure 3.9b).

In contrast, a solution that has a higher concentration of solutes than another solution is said to be hypertonic (hyper (over)). Water molecules will tend to diffuse into a hypertonic solution to dilute the high solute concentration and bring it closer to the concentration of the solution with less solute. For example, red blood cells placed in a hypertonic solution will shrivel and lose volume as osmosis will cause an overall movement of water out of the cells and into the high solute concentration of the hypertonic solution (Figure 3.9c). The shrinkage of cells is called crenation.

Figure 3.9 Concentration of Solutions A hypertonic solution has a solute concentration higher than another solution. An isotonic solution has a solute concentration equal to another solution. A hypotonic solution has a solute concentration lower than another solution.

The rupture of red blood cells is called hemolysis (hemo (blood), lysis (rupture)). The organ systems of your body, particularly the kidneys, work to keep homeostatic balance in the solute and water concentrations of your body to maintain an internal environment in which all of the body’s cells are in an isotonic solution. Hyponatremia (natrium (salt)) is a condition in which the concentration of sodium in your blood plasma becomes abnormally low. Hyponatremia can be caused by various factors, ranging from underlying medical conditions such as heart failure and kidney diseases, severe burns, to drinking too much water. In hyponatremia, your ECF becomes too hypotonic, and your cells begin to swell due to osmosis moving water from the ECF into your cells. Hyponatremia can lead to headache, nausea, convulsions, and if severe, even to coma and death (https://medlineplus.gov/ency/article/000394.htm). The imbalance of electrolytes seen in hyponatremia is a danger to athletes competing in long-duration, high-intensity exercise events such as an Ironman Worldchampionship in Kona (Figure 3.10).

Figure 3.10. Ironman athletes competing on Queen Kaʻahumanu highway on the big island https://commons.wikimedia.org/wiki/File:2009_Ironman_-_Big_Island_Hawaii._Mauna_Lani_waypoint_(cropped).jpg]

Active Processes

Active Transport

For all of the cell transport methods described above, the cell expends no energy since substances are moving from high to low concentrations. Membrane proteins that aid in the passive transport of substances do so without the use of ATP or other forms of stored energy in the cell. During primary active transport, the energy contained within ATP is used to move a substance across a membrane. Primary active transport is often done with the help of protein carriers and moves substances against their concentration gradient (that is, from low to high concentrations). One of the most common types of active transport involves proteins that serve as molecular pumps. The word “pump” may be familiar if you have tried to inflate a bicycle tire or a basketball. When you pump air into those objects, you try to move air from the outside environment at a lower concentration and push it into the inside of the tire or ball which is at a much higher concentration. This movement doesn’t happen by itself, to move substances from a low to a high concentration (the opposite of diffusion) energy needs to be utilized. As you pump more air into the tire or ball, you may notice that if you stop pumping, the air will try to rush out of the object. Therefore you are using energy to pump against forces that try to move the air from high pressure to low pressure. Similarly, energy from ATP is required for molecular pumps to transport molecules or ions across the membrane, usually against their concentration gradients (from an area of low concentration to an area of high concentration).

An electrical gradient is a difference in electrical charge across a space. In the case of nerve cells, for example, the electrical gradient exists between the inside and outside of the cell, with the inside being negatively charged relative to the outside. The negative electrical gradient is maintained because we are pumping both sodium ions (Na+) and potassium ions (K+) against their concentration gradients from a high to low concentration with the sodium-potassium pump (Figure 3.11). The sodium-potassium pump, which is also called Na+/K+ ATPase, transports Na+ out of a cell while moving K+ into the cell. This process uses ATP and this process is so important for nerve cells that it accounts for the majority of their ATP usage. The sodium-potassium pump is an important ion pump found in the membranes of many types of cells. Imagine that you have one hundred of these pumps pumping just one cycle: you will end up with 300 Na+ outside and 200 K+ inside the cell from this one pumping cycle. Now that we learn about what primary active transport does, you might ask why our cells do so? The question will be answered as you read on.

Figure 3.11 Sodium-Potassium Pump The sodium-potassium pump is found in many cell (plasma) membranes. Powered by ATP, the pump moves sodium and potassium ions in opposite directions, each against its concentration gradient. In a single cycle of the pump, three sodium ions are extruded from and two potassium ions are imported into the cell.

The reason why primary active transport uses energy to move ions across the cell membrane against their gradient is because the cells can use these buildup ions to carry other molecules into or out of the cells which might have been unfavorable. Active transport pumps work together with other active or passive transport systems to move substances across the membrane. For example, the sodium-potassium pump maintains a high concentration of Na+ outside of the cell. Therefore, if the cell needs Na+, all it has to do is open a passive sodium ion channel, as the concentration gradient of Na+ will drive them to diffuse into the cell. In this way, the action of an active transport pump (the sodium-potassium pump) powers the passive transport of Na+ by creating a concentration gradient. When active transport powers the transport of another substance in this way, it is called secondary active transport. Symporters are secondary active transporters that move two substances in the same direction (Figure 3.12). For example, the sodium-glucose symporter uses Na+ to “pull” glucose molecules into the cell. Because cells use and store glucose for energy, glucose is typically at a higher concentration inside of the cell than outside. However, due to the action of the sodium-potassium pump, Na+ will easily diffuse into the cell when the symporter is opened. The symporters harness the energy from the flood of Na+ into the cell (following its concentration gradient) to also move glucose against its concentration gradient. Conversely, antiporters are secondary active transport systems that transport substances in opposite directions (Figure 3.12). For example, the sodium-hydrogen ion antiporter uses the energy from the inward flood of Na+ to move hydrogen ions (H+) out of the cell. The sodium-hydrogen antiporter is used to maintain the pH of the cell’s interior.

Figure 3.12 Symporters and Antiporters (By CNX OpenStax — http://cnx.org/contents/GFy_h8cu@10.53:rZudN6XP@2/Introduction, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=49924729)

Vesicle Transport

Other forms of active transport do not involve membrane carriers. As the substances that need to cross the cell are much too large to fit through a membrane protein. Endocytosis (bringing “into the cell”) is the process of a cell ingesting material by enveloping it in a portion of its cell membrane and then pinching off that portion of the membrane (Figure 3.13). Once pinched off, the portion of the membrane and its contents becomes an independent, intracellular vesicle. A vesicle is a membranous sac — a spherical and hollow organelle bounded by a lipid bilayer membrane. Endocytosis often brings materials into the cell that must be broken down or digested. Phagocytosis (cell eating) is the endocytosis of large particles. Many immune cells engage in phagocytosis of invading pathogens. Like little Pac-Man, their job is to patrol body tissues for unwanted matter, such as invading bacterial cells, phagocytize them, and digest them. In contrast to phagocytosis, pinocytosis (cell drinking), or bulk-phase endocytosis, brings fluid containing dissolved substances into a cell through membrane vesicles. Phagocytosis and pinocytosis take in large portions of extracellular material, and they are typically not highly selective in the substances they bring in. Cells regulate the endocytosis of specific substances via receptor-mediated endocytosis. As the name implies, this type of endocytosis results in internalizing only a certain substance that are bound to receptors on the cell surface. Once the surface receptors have bound sufficient amounts of the specific substance, the cell will endocytose the part of the cell membrane containing the receptor-ligand complexes. Iron, a required component of hemoglobin, is endocytosed by red blood cells in this way.

Figure 3.13 Three Forms of Endocytosis Endocytosis is a form of active transport in which a cell envelopes extracellular materials using its cell membrane. (a) In phagocytosis, which is relatively nonselective, the cell takes in a large particle. (b) In pinocytosis, the cell takes in small particles in the fluid. (c) In contrast, receptor-mediated endocytosis is quite selective. When external receptors bind a specific ligand, the cell responds by endocytosing the ligand.

In contrast with endocytosis, exocytosis (taking out of the cell) is the process of a cell exporting material using vesicular transport (Figure 3.14). Many cells manufacture substances that must be secreted comparable to a factory manufacturing a product for export. These substances are typically packaged into membrane-bound vesicles within the cell. When the vesicle membrane fuses with the cell membrane, the vesicle releases its contents into the interstitial fluid. The vesicle membrane then becomes part of the cell membrane. Cells of the stomach and pancreas produce and secrete digestive enzymes through exocytosis. Endocrine cells produce and secrete hormones that are sent throughout the body, and certain immune cells produce and secrete large amounts of histamine, a chemical important for immune responses via the method of exocytosis.

Figure 3.14 Exocytosis Exocytosis is similar to endocytosis in reverse. Material destined for export is packaged into a vesicle inside the cell. The membrane of the vesicle fuses with the cell membrane, and the contents are released into the extracellular space.

Another way of moving molecules into, across, and out of the cells is through transcytosis. In this case, a molecule moves through the cell by endocytosis on one side and exits through exocytosis at the other end. For example, some maternal antibodies travel across the cells of the blood vessels into fetal circulation during pregnancy. This helps the growing fetus fight against foreign pathogens.

Figure 3.15: Normal and Mutant CFTR channels Illustration showing normal and mutant CFTR channels, with cross-sections of the effect on the airway. (Also see www.yourgenome.org/facts/what-is-cystic-fibrosis)

In normal lung tissue, the movement of Cl– out of the cell maintains a Cl–-rich, negatively charged environment immediately outside of the cell. This is particularly important in the epithelial lining of the respiratory system. Respiratory epithelial cells secrete mucus, which serves to trap dust, bacteria, and other debris.

If the CFTR channel is absent, Cl– ions are not transported out of the cell in adequate numbers, thus preventing them from drawing positive ions. The absence of ions in the secreted mucus results in the lack of a normal water concentration gradient. Thus, there is no osmotic pressure pulling water into the mucus. The resulting mucus is thick and sticky, and the ciliated epithelia cannot effectively remove it from the respiratory system. Passageways in the lungs become blocked with mucus, along with the debris it carries. Bacterial infections occur more easily because bacterial cells are not effectively carried away from the lungs.]

3.3 Cytoplasm: Cellular Organelles and Cytosol

Now that you have learned about the cell membrane that surrounds all cells, you can dive inside a prototypical human cell to learn about its internal components and their functions. Cytosol, the jelly-like substance within the cell, provides the fluid medium necessary for biochemical reactions. Eukaryotic cells, including all animal cells, also contain various cellular organelles (Figure 3.16). An organelle is one of several different types of structures in the cell, each performing a unique function. The organelles and cytosol, taken together, compose the cell’s cytoplasm as in department buildings and campus space compose the college campus.

Figure 3.16: A color-labeled Human cell with fluorescent organelles and membrane A fluorescence image of a human cell showing membrane (white), nucleus (blue), endoplasmic reticulum (red), mitochondria (green), Golgi (yellow), and peroxisomes (pink). By Vojtěch Dostál — Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=66726176)

Organelles

Although each organelle carries out specific functions In the human cells, you will find that some organelles are surrounded by lipid bilayers and are filled with fluids. An example of a membranous organelle is mitochondria. On the other hand, ribosomes and proteasomes are non-membranous organelles in which they are not surrounded by membranes. In fact, these organelles are made from proteins.

The Endomembrane System

A set of three major organelles together form a system within the cell called the endomembrane system. These organelles work together to perform various cellular jobs, including the task of producing, packaging, and exporting certain cellular products. The organelles of the endomembrane system include the endoplasmic reticulum (ER), Golgi apparatus, and vesicles.

The endoplasmic reticulum (ER) is a multifunctional organelle with a system of channels that is continuous with the nuclear membrane (or nuclear envelope) covering the nucleus and composed of the same lipid bilayer material. The ER can be thought of as a series of winding thoroughfares similar to the waterway canals in Venice. The ER provides passages throughout much of the cell that function in transporting, synthesizing, and storing materials. The winding structure of the ER results in a large membranous surface area that supports its many functions (Figure 3.17a).

Figure 3.17 Endoplasmic Reticulum (ER) (a) The ER is a winding network of thin membranous sacs found in close association with the cell nucleus. The smooth and rough endoplasmic reticula are very different in appearance and function (source: mouse tissue). (b) Rough ER is studded with numerous ribosomes, which are sites of protein synthesis (source: mouse tissue). EM × 110,000. (c) Smooth ER synthesizes phospholipids, steroid hormones, regulates the concentration of cellular Ca++, metabolizes some carbohydrates, and breaks down certain toxins (source: mouse tissue). EM × 110,510. (Micrographs provided by the Regents of University of Michigan Medical School © 2012)

The endoplasmic reticulum can exist in two forms: rough and smooth ER. These two types of ER perform different functions. Rough ER (RER) is called “rough” because its membrane is dotted with organelles called ribosomes giving it a bumpy appearance (see Figure 3.17b). A ribosome is a non-membranous organelle that is involved in protein synthesis which will be covered later in the chapter. In brief, the RER is responsible for producing membrane proteins or proteins that are destined for transport outside of the cell or another organelle. Usually, sugars are attached to these proteins producing glycoproteins. Free-floating ribosomes in the cytoplasm produce proteins that will be utilized within the cytoplasm.

Smooth ER (SER) lacks these ribosomes (Figure 3.17c) and does not carry out protein synthesis. One of the main functions of the SER is in the synthesis of fatty acids and steroids. For this reason, cells that produce large quantities of steroids, for instance, contain large amounts of SER. In addition, SER also stores and regulates the concentration of cellular Ca++, a function extremely important in cells of the nervous system and muscle contraction. The SER also plays a role in carbohydrate metabolism and breaking down some toxins. Overall, the endoplasmic reticulum is responsible for the protein and lipid homeostasis of the cell.

The Golgi apparatus is responsible for sorting, modifying, and packaging the products that come from the rough ER, much as a post office on a college campus handles mail. The Golgi apparatus looks similar to stacked flattened discs, a bit like oddly shaped pancakes. As with the ER, these discs are membranous. The Golgi apparatus has two distinct sides, each with a different role. The entry (cis) face of the apparatus is closer to the RER and receives the products in vesicles. These products are sorted through the apparatus and are then released from the opposite side, the exit (trans) face after being repackaged into new vesicles. If the product is to be exported from the cell, the vesicle migrates to the cell surface and fuses to the cell membrane, and the cargo is secreted (Figure 3.18).

Figure 3.18 Golgi Apparatus (a) The Golgi apparatus manipulates products from the rough ER and also produces new organelles called lysosomes. Proteins and other products of the ER are sent to the Golgi apparatus, which organizes, modifies, packages, and tags them. Some of these products are transported to other areas of the cell and some are exported from the cell through exocytosis. Enzymatic proteins are packaged as new lysosomes (or packaged and sent for fusion with existing lysosomes). (b) An electron micrograph of the Golgi apparatus.

Some of the protein products packaged by the Golgi includes digestive enzymes that are meant to remain inside the cell for use in breaking down certain materials. The enzyme-containing vesicles released by the Golgi apparatus form new lysosomes or fuse them with existing lysosomes. A lysosome (lyse (to break open), soma (body)) is an organelle that contains digestive enzymes that break down and digest unneeded cellular components such as a damaged organelle and breaking down foreign material engulfed by the cell. For example, when certain immune defense cells (white blood cells) phagocytize bacteria, the bacterial cell is transported into a lysosome and digested by the enzymes inside. Lysosomal enzymes have a lower pH of approximately 5 which is lower than the cytosolic pH of 7. Recall that a lower pH value indicates the presence of more hydrogen ions, so you can think of lysosomes as the stomach of the cell. Concerning our college analogy, a lysosome is similar to a recycling crew that breaks down old and worn-out structures on your campus.

Organelles for Energy Production, Detoxification, and Recycling

In addition to the jobs performed by the endomembrane system, the cell has many other important functions. Living “breathing” cells are constantly metabolizing and require a system that provides delivery of oxygen or nutrients as well as transport of waste products out and away from the cell. These delivered nutrients are converted to chemical energy in the form of adenosine triphosphate (ATP). Another important function of the cell is detoxification and recycling. Humans take in all sorts of toxins from the environment and also produce harmful chemicals as byproducts of cellular processes. Also, damaged or unneeded proteins are being recycled in the cell.

A mitochondrion (pleural = mitochondria) is a membranous, bean-shaped organelle that is the “energy transformer” or powerhouse of the cell or the power plant that supports the college. Mitochondria consist of an outer lipid bilayer membrane as well as an additional inner lipid bilayer membrane (Figure 3.19). The inner membrane is highly folded into winding structures with a great deal of surface area, called cristae. It is along this inner membrane that a series of proteins, enzymes, and other molecules perform the biochemical reactions of cellular respiration. These reactions convert the energy stored in nutrient molecules (such as glucose) into ATP, which provides usable cellular energy to the cell. Cells use ATP constantly and so the mitochondria are constantly at work.

Oxygen molecules are required during the last step of cellular respiration, which is why you must constantly breathe them in. One of the organ systems in the body that uses huge amounts of ATP is the muscular system because ATP is required to sustain muscle contraction. As a result, muscle cells are packed with mitochondria. Nerve cells also need large quantities of ATP to run their sodium-potassium pumps. Therefore, an individual neuron will be loaded with over a thousand mitochondria. On the other hand, a bone cell, which is not nearly as metabolically active, might only have a couple of hundred mitochondria. On the other hand, mature red blood cells have no mitochondria!

Figure 3.19 Mitochondrion The mitochondria are the energy-conversion factories of the cell. (a) A mitochondrion is composed of two separate lipid bilayer membranes. Along the inner membrane are various molecules that work together to produce ATP, the cell’s major energy currency. (b) An electron micrograph of mitochondria. EM × 236,000. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

From the previous chapter, we learned that the nucleus stores the genetic information for the cell. You may be surprised to hear that mitochondria have their own mitochondrial DNA. Since mitochondrial DNA is inherited from the maternal parent, it is being used to trace the maternal lineage. It is known that genetic mutation and other factors can cause malfunctioning of the mitochondria and result in mitochondrial disease. When this happens, cellular fuels are not being converted into energy by the mitochondria and the cellular and tissue components of the organs are unable to function normally. For example, muscle contraction and nerve conduction will be impacted by the deficiency of ATP. Since the mitochondria are responsible for the majority of energy synthesis in cells the symptoms of mitochondrial diseases may include poor growth, muscle weakness, neurological problems, and more. (https://my.clevelandclinic.org/health/diseases/) (https://medlineplus.gov/mitochondrialdiseases.html)

Have you ever wondered why humans age? What is happening on a cellular level as we age? We will briefly tap into another aspect of mitochondrial function as it comes into play with aging. This is a natural process with some known and many unknown factors involved. Scientists have been studying mitochondria function as it relates to human aging. Through research, it is observed that there is a decrease in mitochondrial function and an increase in mitochondrial mutation with aging. Since the mitochondria are responsible for energy production, there is a chance of generating reactive oxygen species (ROS) during this process. Examples of ROS include the hydroxyl radical (OH-.), hydrogen peroxide (H2O2), and superoxide (O2-.). They have unpaired electrons and called free radicals. They are extremely reactive and can oxidize cellular proteins, lipids, and DNA, causing cellular damage and even cell death. Free radicals are thought to play a role in many destructive processes in the body, from cancer to coronary artery disease. When mitochondrial DNA is damaged, it may affect the mitochondria function and increases the generation of ROS. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779179/)

Our cells do have a way to lower the concentration of ROS. There is a Hazardous Materials Management office on campus that takes care of these toxic materials that may be generated in labs on campus. The hazardous materials management office can be compared to the peroxisome. As with lysosomes, a peroxisome is a membrane-bound cellular organelle that contains mostly oxidases, a group of enzymes that can oxidize substances such as alcohol (Figure 3.20). In contrast to the digestive enzymes found in lysosomes, the enzymes within peroxisomes serve to transfer hydrogen atoms from various molecules to oxygen. For example, when alcohol is detoxified in the peroxisomes of liver cells, we produce hydrogen peroxide (H2O2). However, hydrogen peroxide is still toxic, thus we have a catalase (another peroxisomal enzyme) that further detoxifies it into water and oxygen gas. In this way, peroxisomes neutralize poisons such as alcohol.

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Figure 3.20 Peroxisome Peroxisomes are membrane-bound organelles that contain an abundance of enzymes for detoxifying harmful substances and lipid metabolism. (By CNX OpenStax — https://cnx.org/contents/5CvTdmJL@4.4, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=53712533)

Peroxisomes oversee reactions that neutralize free radicals. Peroxisomes produce large amounts of toxic H2O2 in the process, but peroxisomes contain catalase enzymes that convert H2O2 into water and oxygen. These byproducts are safely released into the cytoplasm. Similar to miniature sewage treatment plants, peroxisomes neutralize harmful toxins so that they do not wreak havoc in the cells. The liver is the organ primarily responsible for detoxifying the blood before it travels throughout the body, and liver cells contain an exceptionally high number of peroxisomes.

Defense mechanisms such as detoxification within the peroxisome and certain cellular antioxidants serve to neutralize many of these molecules. Some vitamins and other substances found primarily in fruits and vegetables have antioxidant properties. Antioxidants work by being oxidized themselves, halting the destructive reaction cascades initiated by the free radicals. Sometimes though, ROS accumulate beyond the capacity of such defenses.

Oxidative stress is the term used to describe damage to cellular components caused by ROS. Due to their characteristic unpaired electrons, ROS can set off chain reactions where they remove electrons from other molecules, which then become oxidized and reactive, and do the same to other molecules, causing a chain reaction. ROS can cause permanent damage to cellular lipids, proteins, carbohydrates, and nucleic acids. Damaged DNA can lead to genetic mutations and even cancer. A mutation is a change in the nucleotide sequence in a gene within a cell’s DNA, potentially altering the protein coded by that gene. Other diseases believed to be triggered or exacerbated by ROS include Alzheimer’s disease, cardiovascular diseases, diabetes, Parkinson’s disease, arthritis, Huntington’s disease, and schizophrenia, among many others. It is noteworthy that these diseases are largely age-related. Many scientists believe that oxidative stress is a major contributor to the aging process.

In our cells, not all newly synthesized proteins are folded correctly. We have unneeded, damaged, and faulty proteins that need to be addressed. Proteasomes are a protein complex (i.e. a non-membranous organelle) that recycles these sets of proteins by proteolysis, breaking the peptide bonds. They use ubiquitin, a protein, to tag the recycled proteins for proteolysis (Figure 3.21). In our cells, we have thousands of these proteasomes in the cytosol and nucleus. They play a role in keeping the cell cycle in check by quickly removing regulatory proteins as well as during the process of apoptosis. Dysfunction of the proteasomes has been implicated in Parkinson’s diseases and Alzheimer’s disease where researchers observe an accumulation of misfolded proteins in the nervous system. (https://en.wikipedia.org/wiki/Proteasome)

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Figure 3.21 Proteasome (a) The recycling function of the proteasome with ubiquitins tagging the target protein. (b) The blue portion of the proteasome is where proteolysis occurs.

(By CNX OpenStax — http://cnx.org/contents/GFy_h8cu@10.53:rZudN6XP@2/Introduction, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=49929343)

(b) structure of a proteasome. (By Thomas Splettstoesser (www.scistyle.com) — Based on atomic coordinates of PDB 1FNT, rendered with open source molecular visualization tool PyMol (www.pymol.org), CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=1290287)

Cytoskeleton

Much as the bony skeleton structurally supports the human body, the cytoskeleton helps the cells to maintain their structural integrity. A cytoskeleton is a group of fibrous proteins that provide structural support for cells, such as the steel beams of a building, but this is only one of the functions of the cytoskeleton. Cytoskeletal components are also critical for cell movement, cell reproduction, and moving substances within the cell. The cytoskeleton forms a complex thread-like network throughout the cell consisting of three different kinds of protein-based filaments: microfilaments, intermediate filaments, and microtubules (Figure 3.22).

Figure 3.22 The Three Components of the Cytoskeleton The cytoskeleton consists of (a) microtubules, (b) microfilaments, and (c) intermediate filaments. The cytoskeleton plays an important role in maintaining cell shape and structure, promoting cellular movement, and aiding cell division.

Microtubules

The thickest of the three cytoskeletal proteins is the microtubule. The microtubule is composed of subunits of a protein called tubulin. Microtubules maintain cell structure and play a role in moving organelles and vesicles within a cell. Microtubules also make up two types of cellular appendages important for motion: cilia and flagella (Figure 3.23). Cilia (singular = cilium) are found on many cells of the body, including the cells that line the airways of the respiratory tract. Here, cilia move rhythmically, moving waste materials such as dust, mucus, and bacteria upward away from the lungs. Flagella (singular = flagellum) are appendages that specialize in cell locomotion. The only flagellated cells in humans are sperm cells.

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Figure 3.23 Cilia and flagella (a) cilia, (b) flagellum on human sperm cells. (https://commons.wikimedia.org/wiki/File:Figure_39_01_10.jpg and https://commons.wikimedia.org/wiki/File:Sperm-20051108.jpg)

A centrosome is a structure responsible for organizing microtubules. It is composed of two short, identical microtubule structures called centrioles. Microtubules grow out from the centrioles by adding more tubulin subunits, like adding additional links to a chain, to assist with the separation of DNA during cell division (Figure 3.24).

Figure 3.24 Centromere An arrow on the bottom right corner pointing at the centrosome next to a nucleus of a cell. (Public Domain, https://commons.wikimedia.org/w/index.php?curid=442499)

In contrast with microtubules, the microfilament is a thinner type of cytoskeletal filament (see Figure 3.22b). The primary component of a microfilament is a protein called actin which links together and forms a fiber-like structure. Actin fibers (twisted chains of actin filaments) are a large component of muscle tissues. Microfilaments also have an important role during cell division. When a cell is about to divide these filaments create a constricting band that eventually splits the cell down the middle.

The final cytoskeletal filament is the intermediate filament. As its name would suggest, an intermediate filament is a filament intermediate in thickness between the microtubules and microfilaments (see Figure 3.22c). Intermediate filaments are made up of long fibrous subunits of a protein that are wound together like the threads that compose a rope. One example of a protein that forms intermediate filaments is keratin found in hair, nails, and skin. Intermediate filaments, along with the microtubules, are important for maintaining cell shape and structure. Unlike the microtubules, which resist compression, intermediate filaments resist tension — the forces that pull apart cells. There are many cases in which cells are prone to tension, such as when skin cells are pulled in different directions. Intermediate filaments also help anchor organelles together within a cell and link adjacent cells to other cells by forming special cell-to-cell junctions.

3.4 The Nucleus

The nucleus (center) is the largest and most prominent organelle of a cell (Figure 3.25). The nucleus is generally considered the control center of the cell because it stores the genetic instructions for manufacturing proteins. Most cells in the body contain only one nucleus. Interestingly, some cells in the body, such as muscle cells, contain more than one nucleus, and others, such as mammalian red blood cells (RBCs), eject it as they mature to make space for the large numbers of hemoglobin molecules.

Inside the nucleus lies the DNA which is a blueprint for cell structure (anatomy) and function (physiology). Everything a cell can do and all of the products it can make is determined by the DNA in the nucleus. Except for germ cells such as sperm and oocytes, every cell nucleus in your body contains the complete set of your DNA. When a cell divides, the DNA must be duplicated by a process called DNA replication so that each new cell receives a full complement of DNA. The following section will explore the structure of the nucleus and its contents, as well as the process of DNA replication.

Figure 3.25 The Nucleus The nucleus is the control center of the cell. The nucleus of living cells contains the genetic material that determines the entire structure and function of that cell.

The nucleus is surrounded by the nuclear envelope. The nuclear envelope is a double membrane, meaning it has two layers. This bilayer consists mostly of phospholipid molecules with a thin fluid space in between. Nuclear pores span the double membrane creating a tiny passageway for proteins, RNA, and solutes to move between the nucleus and the cytoplasm. The DNA, however, is too large to pass through these pores. Inside the nuclear envelope is nucleoplasm containing many dissolved solutes including nucleotides (the monomers or building blocks of DNA and RNA). Due to the abundance of DNA, the nucleus typically appears a dark purple or bluish color on microscope images. Within the nucleus, there also can be an even darker-staining mass called a nucleolus (the small center within the center, plural = nucleoli). The nucleolus is a region of the nucleus that is responsible for manufacturing the RNA necessary for the construction of ribosomes.

Negatively charged genomic DNA molecules wrap around positively charged proteins called histones. These long threads are called chromatin during most cell functions (Figure 3.26). However, when a cell is in the process of division, the chromatin condenses by twisting into structures called chromosomes. This allows for the chromosomes to be moved around during division without damaging the DNA molecules. Every human somatic (body) cell has 46 chromosomes in its nuclei. Genetics and sex cell (gametes, sperm, and ova) division are covered in the last chapter. In this chapter, we will focus on DNA replication, protein synthesis, and cell division.

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Figure 3.26 DNA Macrostructure (a) Strands of DNA are wrapped around supporting histones. These proteins are increasingly bundled and condensed into chromatin, which is packed tightly into chromosomes when the cell is ready to divide. (b) 23 pairs of human chromosomes. (By National Human Genome Research Institute (NHGRI) from Bethesda, MD, USA — NHGRI Fact Sheet: Chromosomes, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=52360084)

DNA Replication

Shared characteristics of all life forms include growth, repair, and reproduction. Human growth is apparent in children, but even adult humans generate billions of new cells every day to replace the old damaged cells. For example, skin cells divide frequently to replace those that are constantly being rubbed off. When cells divide for growth and repair, each new daughter cell has a full complement of DNA (they are essentially the same as the original cell). The structure of DNA makes this possible by allowing for a rather elegant replication method, one that conserves the original DNA sequence for both daughter cells.

A DNA molecule is made of two strands that complement each other. You learned in the previous chapter that each strand of DNA is composed of a sugar-phosphate backbone with nitrogenous bases branching out from it. The two strands are oriented in an antiparallel orientation, meaning that their backbones run in opposite directions (think of a two-way street, adjacent cars are parallel but pointing in opposite directions). It is the branching nitrogenous bases that participate in the complementary binding between the strands. When one nitrogenous base binds another by hydrogen bonds, it is called base pairing (Figure 3.27). Adenine (A) forms two hydrogen bonds with thymine (T), and cytosine (C) forms three hydrogen bonds with guanine (G). Because of this specific base pairing (A binds T, C binds G) if you know the sequence of one strand you could decipher the sequence of the complementary strand. For example, if one strand has a region with the sequence ATGC, then the sequence of the complementary strand must be TACG. This complementary base pairing is strong enough to hold the two strands together but weak enough to be separated easily for gene expression or DNA replication. Not only are the nitrogenous bases responsible for holding the two strands of the DNA molecule together, but the particular sequence of bases is also a genetic code!

The entire sequence of the human genome was completed by The Human Genome Project (HGP) in 2003. It took an international team of researchers nearly 13 years to sequence the three billion DNA base pairs in the human genome and is considered by many to be one of the most ambitious scientific undertakings of all time. This information has helped us make huge strides in our understanding of human biology and diseases and led to the development of new diagnostic tools and therapeutic drugs.

Figure 3.27 Molecular Structure of DNA The DNA double helix is composed of two complementary strands. The strands are bonded together via their nitrogenous base pairs using hydrogen bonds.

During cell division, both daughter cells must receive the full complement of DNA as found in the original cell. Therefore, DNA must be copied precisely before cell division can take place. The process of copying all genomic DNA is called DNA replication (Figure 3.28).

Figure 3.28 DNA Replication DNA replication faithfully duplicates the entire genome of the cell. During DNA replication, many different enzymes work together to pull apart the two strands so each strand can be used as a template to synthesize new complementary strands. The two new daughter DNA molecules each contain one pre-existing strand and one newly synthesized strand. Thus, DNA replication is said to be “semiconservative.”

Firstly, the two complementary DNA strands are separated, much like unzipping a zipper. Special enzymes, including helicase, untwist and separate the two strands. Using the specific pairing of the nitrogenous bases, a new complementary strand is built using the old one as a template. The enzyme DNA polymerase adds free nucleotides to the end of the newly growing strand. This continues until DNA polymerase reaches the end of the chromosome and thus produces two double-stranded DNA molecules. Each new DNA molecule contains one strand from the original molecule and one newly synthesized strand. The term for this mode of replication is “semiconservative,” because half of the original DNA molecule is conserved in each new DNA molecule. DNA replication of a single chromosome occurs quickly by using several enzymes at once and all chromosomes are replicated simultaneously. As you might imagine, DNA replication must be precise so that newly made cells in the body contain the same genetic material as their parent cells. Mistakes made during DNA replication, such as the addition of a non-pairing nucleotide, have the potential to render a gene dysfunctional. Fortunately, there are mechanisms in place to minimize such mistakes including a DNA proofreading process that uses special enzymes. Once the process of DNA replication is complete, the cell is ready to divide. You will explore the process of cell division later in the chapter.

3.5 Protein Synthesis

It was mentioned earlier that DNA is a “blueprint” for cell anatomy and physiology. DNA contains the information necessary for the cell to build proteins. Proteins are made up of long strands of amino acids. The order of amino acids determines the protein shape, and the protein shape determines the protein function. Different proteins serve different functions; structural proteins determine the cell shape, membrane-embedded proteins allow movement of materials in and out of the cell, enzymes catalyze (speed up) biochemical reactions, etc. Some enzymes mediate transcription and translation, the major steps of protein production. Therefore, among the various roles proteins play within a cell, they also determine which proteins are made!

A genome is a cell’s entire DNA sequence (all chromosomes). A proteome is a cell’s entire protein profile. A gene is a specific segment of DNA that provides the genetic information to build a specific protein. The phrase “gene expression” means a cell is producing a protein. Even though all nuclei contain the same genes the different types of cells around the body produce different proteins (they express different genes). For example, the beta cells of the pancreas make insulin, a peptide hormone. No other cells do that even though they all have the gene. Within a gene some sequences indicate where the gene starts and ends. Other segments of DNA around a gene influence how frequently a gene is copied.

Recall that proteins are polymers (a long chain) of amino acid monomers. The sequence of bases in a gene (the sequence of A, T, C, G nucleotides) translates to an amino acid sequence. A codon is a sequence of DNA three bases long (triplet) that codes for a specific amino acid. Similar to how the three-letter code d-o-g signals the image of a dog, the three-letter DNA base code signals the use of a particular amino acid. For example, the DNA triplet CAC (cytosine, adenine, cytosine) specifies the amino acid valine. A gene is composed of multiple triplets in a unique sequence that represents the sequence of amino acids in a protein (Figure 3.28). The mechanism by which cells turn DNA code into protein is a two-step process involving RNA.

Transcription: DNA to mRNA

DNA is housed within the nucleus, and protein synthesis takes place in the cytoplasm, thus there must be some sort of intermediate messenger that carries the genetic information from the nucleus to the site where proteins are made. This intermediate messenger is messenger RNA (mRNA). There are other types of RNA, each serving different functions of protein synthesis. tRNA transfers amino acids to the site of protein synthesis and rRNA is part of the ribosome organelle that binds to mRNA. You may recall from the previous chapter that the structure of RNA is similar to DNA with a few small exceptions. For one thing, RNA is usually single-stranded (it contains no complementary strand). Second, the ribose sugar in RNA contains an additional oxygen atom compared with DNA (the D in DNA stands for deoxyribose). Finally, instead of the nitrogenous base thymine (T), RNA contains the base uracil (U).

Gene expression begins with transcription which is the process of making mRNA (Figure 3.29). It is called transcription because mRNA and DNA are both nucleic acid molecules. The mRNA is a transcript (a copy) of the gene’s DNA code. Transcription is similar to DNA replication but only a small segment (the gene) will be copied instead of the whole DNA molecule. In a small region the DNA unwinds and the strands separate. A region near the beginning of the gene is called a promoter and it is a binding site for RNA polymerase. One strand, referred to as the coding strand, is the one that is transcribed into mRNA. RNA polymerase begins coping at the start codon and polymerizes nucleotides to generate mRNA (aka transcript or the message). This process stops at the stop codon (terminator sequence). mRNA is not double-stranded but it does have a secondary structure (it is folded). This folding stabilizes and separates the mRNA from the gene/RNA polymerase complex.

Figure 3.29 Transcription — from DNA to mRNA In the first of the two stages of making protein from DNA, a gene on the DNA molecule is transcribed into a complementary mRNA molecule.

The newly released molecule is called pre-mRNA because it still must be “processed” before leaving the nucleus and proceeding to protein synthesis. It undergoes a process called splicing to remove gene segments that are non-coding (do not code for amino acid sequence) by a non-membranous organelle called the spliceosome (Figure 3.30). Other types of mRNA processing include capping (with a guanine molecule) on the leading end and adding a poly-A tail (series of adenine nucleotides) on the other end.

Figure 3.30 Splicing RNA In the nucleus, a structure called a spliceosome cuts out introns (non-coding regions) within a pre-mRNA transcript and reconnects the exons.

Translation: RNA to Protein

Like translating a book from one language into another, the codons on a strand of mRNA must be translated from the language of nucleotides into the language of amino acids. Translation is the process of linking amino acids together into a long chain called a polypeptide. The sequence of amino acids is dictated by the mRNA nucleotide sequence. Ribosomes have a small and a large subunit and each one is made of proteins rRNA. When mRNA binds to the rRNA of the ribosome, the two subunits come together and clamp onto the mRNA. Then tRNA transfers amino acids to the ribosome and attaches each new amino acid to the last, building the polypeptide chain one by one. tRNA has a binding site for a specific amino acid and a base sequence that matches the codon on the mRNA. The tRNA nucleotides that are complementary to the mRNA codons are called the anticodon. (Figure 3.31).

Figure 3.31 Translation from RNA to Protein During translation, the mRNA transcript is “read” by a functional complex consisting of the ribosome and tRNA molecules. tRNAs bring the appropriate amino acids in sequence to the growing polypeptide chain by matching their anticodons with codons on the mRNA strand.

After each amino acid is added, the tRNA is released and the mRNA moves one codon over in the ribosome to open a space for the next tRNA to arrive. This process continues until the final codon on the mRNA is reached and triggers the release of the complete, newly synthesized polypeptide. You may recall from the previous chapter that if the length of the amino acid polymer is sufficiently long, it folds in on itself producing a tertiary structure called proteins. Shorter sequences of amino acids are simply called peptides. Some proteins are translated into the cytoplasm and remain there. Proteins destined for other locations are translated by ribosomes bound to the rough ER.

The figure below summarizes the transcription of a gene into mRNA and the translation of mRNA into a protein (Figure 3.32).

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Figure 3.32 From DNA to Protein — Transcription through Translation (a) Transcription within the cell nucleus produces an mRNA molecule, which is modified and then sent into the cytoplasm for translation. The transcript is decoded into a protein with the help of ribosome and tRNA molecules. (b) An example from DNA to RNA to protein shows the sequence of amino acids of the sickle-cell hemoglobin protein. (By Madprime — Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=2068734)

Figure 3.33: The mechanism of mRNA vaccine mRNA vaccine delivers mRNA encoding a part of the viral protein to the cell. The cell carries out translation and produce the viral protein which will be recognized by the immune cells and build immunity in the body.  (By Kuon.Haku — Own work, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=97089536)

3.6 Cell Growth and Division

We all have had experiences when we accidentally stayed out in the sun too long or forgot to use sunscreen and ended up with a mild sunburn. After a few days, the top layer of the skin peels off revealing the newer younger layer. Cells in the body replace themselves over the lifetime of a person. Even without sunburn, the skin cells continue to divide to replace the superficial layers of older skin cells. How does a cell divide? What triggers it to divide? How does it prepare for and complete cell division?

Cell Cycle

The cell cycle is a sequence of events from the moment it is created until it divides into two new cells (Figure 3.34). One “turn” of the cell cycle consists of two distinct phases: interphase and mitosis. Interphase is the period of the cell cycle when the cell is not dividing. At any given time most cells are interphase and many cells will die without ever dividing. Mitosis is the phase when cells divide. The process involves the division of genetic material and the creation of two new, fully functional cells.

Figure 3.34 Cell Cycle The two major phases of the cell cycle include mitosis (designated M), when the cell divides, and interphase when the cell grows and performs all of its normal functions. Interphase is further subdivided into G1, S, and G2 phases.

Interphase is subdivided into 4 phases. G0 phase is for cells that are not actively dividing or never divide, such as some nerve and cardiac muscle cells. Cells that do divide go through phases G1, S, and G2 (Figure 3.33). The G1 phase is the first growth phase in the cycle where a cell grows and accumulates the building blocks of DNA, proteins, and energy reserves to carry out DNA replication. During the S phase (“S” for synthesis), DNA replication occurs and two identical pairs of chromosomes are formed. The cell duplicates some organelles and synthesizes the proteins needed for mitosis during the G2 phase.

After DNA replication during the S phase, the cell ends up with two copies of each chromosome (called sister chromatids) that are physically bound to each other at the centromere. Because a human cell has 46 chromosomes, this phase generates 92 chromatids (46 × 2). Don’t confuse paired sister chromatids (a replicated chromosome) with homologous chromosomes (chromosome pairs inherited separately, one from each parent) (Figure 3.35).

Figure 3.35 Sister chromatids and homologous chromosomes Each cell has paired homologous chromosomes (blue and pink), one from each parent. After DNA replication, each homologous chromosome has two sister chromatids connected at the centromere.

https://commons.wikimedia.org/wiki/File:Chromosome_Terminology.png

Mitosis and Cytokinesis

During mitosis, sister chromatids are separated and move into two identical daughter cells which are then separated. Mitosis is subdivided into prophase, prometaphase, metaphase, anaphase, and telophase (Figure 3.36).

Figure 3.36 Cell Division: Mitosis Followed by Cytokinesis The stages of cell division oversee the separation of identical genetic material into two new nuclei, followed by the division of the cytoplasm. Note that the chromosomes are colored in blue.

Prophase is the first phase of mitosis, during which loosely packed chromatin condenses into darkly staining (visible under the microscope) chromosomes. The familiar chromosome x-shape is the two sister chromatids attached at the centromere. The nuclear envelope also breaks down during prophase. Centrosomes move to the opposite ends of the cell and microtubules start to extend out from the two centrioles inside each centrosome. The structure composed of the centrosomes and their emerging microtubules is called the mitotic spindle and moves the chromosomes as part of the cell division process. This begins in late prophase (called the prometaphase, “before metaphase”) when growing microtubules from the mitotic spindle attach to the kinetochore of the centromere.

During metaphase, the microtubules pull on the kinetochores, aligning all the chromosomes between the two centrosomes which results in the chromosomes lining up at the metaphase plate. Then during anaphase, the pairs of sister chromatids are separated from one another producing separated, individual chromosomes. These chromosomes are pulled to opposite ends of the cell by the centromere. Each end of the cell receives one sister chromatid of the original pair. This ensures that the two new daughter cells are genetically identical. Telophase is the final stage of mitosis. Chromosomes arrive at each pole and start to relax (decondensed), returning to loosely packed chromatin. A nuclear envelope forms around the chromosomes at each pole. Now that mitosis is over, the mitotic spindle breaks apart and disappears. Often overlapping telophase is the process of cytokinesis (cyto (cell), kinesis (movement)) . During this stage, the plasma membrane pinches in between the two nuclei. A band of microfilaments forms around the midline of the cell and squeezes forming a cleavage furrow. When the cleavage furrow separates the cytoplasm into two the daughter cells are formed.

Another type of cell division called meiosis occurs in the reproductive organs of the human body. Meiosis is a special type of cell division that produces gametes, such as sperm and eggs. Its goal is to make daughter cells with exactly half as many chromosomes as the original cell so that when a sperm and egg unite a new cell with unique genetics is created. You will learn about gametes and meiosis when you learn about the reproductive system.

The process of cell division outlined above involves several molecules and events happening in a coordinated sequential fashion. How does a cell accomplish this? There are elaborate and precise control systems that ensure a cell proceeds from one phase to the next. The control system provides “stop” and “advance” signals for the cell, and the loss of cell cycle control can lead to uncontrolled cell division (i.e. cancer).

Chapter Summary

Quiz

Sources:

• OpenStax A&P: https://openstax.org/books/anatomy-and-physiology/pages/3-5-cell-growth-and-division
• Wikipedia
• https://seagrant.soest.hawaii.edu/the-return-of-kuula/
• https://dlnr.hawaii.gov/

Key Terms

active transport

form of transport across the cell membrane that requires input of cellular energy

amphipathic

describes a molecule that exhibits a difference in polarity between its two ends, resulting in a difference in water solubility

anaphase

third stage of mitosis (and meiosis), during which sister chromatids separate into two new nuclear regions of a dividing cell

anticodon

consecutive sequence of three nucleotides on a tRNA molecule that is complementary to a specific codon on an mRNA molecule

antioxidants

compounds that inhibit oxidation, a chemical reaction that can produce free radicals

carrier proteins

Membrane proteins that bind to a substrate and change its shape to transport the substrate across the membrane.

cell cycle

life cycle of a single cell, from its birth until its division into two new daughter cells

cell membrane

membrane surrounding all animal cells, composed of a lipid bilayer interspersed with various molecules; also known as plasma membrane

centriole

small, self-replicating organelle that provides the origin for microtubule growth and moves DNA during cell division

centromere

region of attachment for two sister chromatids

centrosome

cellular structure that organizes microtubules during cell division

channel protein

membrane-spanning protein that has an inner pore which allows the passage of one or more substances

chromatin

substance consisting of DNA and associated proteins

chromosome

condensed version of chromatin

cilia

small appendage on certain cells formed by microtubules and modified for movement of materials across the cellular surface

codon

consecutive sequence of three nucleotides on an mRNA molecule that corresponds to a specific amino acid

concentration gradient

difference in the concentration of a substance between two regions

cytokinesis

final stage in cell division, where the cytoplasm divides to form two separate daughter cells

cytoplasm

internal material between the cell membrane and nucleus of a cell, mainly consisting of a water-based fluid called cytosol, within which are all the other organelles and cellular solute and suspended materials

cytoskeleton

“skeleton” of a cell; formed by rod-like proteins that support the cell’s shape and provide, among other functions, locomotive abilities

cytosol

clear, semi-fluid medium of the cytoplasm, made up mostly of water

diffusion

movement of a substance from an area of higher concentration to one of lower concentration

DNA polymerase

enzyme that functions in adding new nucleotides to a growing strand of DNA during DNA replication

DNA replication

process of duplicating a molecule of DNA

electrical gradient

difference in the electrical charge (potential) between two regions

endocytosis

import of material into the cell by formation of a membrane-bound vesicle

endomembrane system

a group of membranes and organelles in eukaryotic cells that works together to modify, package, and transport lipids and proteins

endoplasmic reticulum (ER)

cellular organelle that consists of interconnected membrane-bound tubules, which may or may not be associated with ribosomes (rough type or smooth type, respectively)

exocytosis

export of a substance out of a cell by formation of a membrane-bound vesicle

extracellular fluid (ECF)

fluid exterior to cells; includes the interstitial fluid, blood plasma, and fluid found in other reservoirs in the body

facilitated diffusion

diffusion of a substance with the aid of a membrane protein

flagellum

appendage on certain cells formed by microtubules and modified for movement

G0 phase

phase of the cell cycle, usually entered from the G1 phase; characterized by long or permanent periods where the cell does not move forward into the DNA synthesis phase

G1 phase

first phase of the cell cycle, after a new cell is born

G2 phase

third phase of the cell cycle, after the DNA synthesis phase

gene

functional length of DNA that provides the genetic information necessary to build a protein

gene expression

active interpretation of the information coded in a gene to produce a functional gene product

genome

entire complement of an organism’s DNA; found within virtually every cell

glycoprotein

protein that has one or more carbohydrates attached

Golgi apparatus

cellular organelle formed by a series of flattened, membrane-bound sacs that functions in protein modification, tagging, packaging, and transport

homologous

describes two copies of the same chromosome (not identical), one inherited from each parent

hydrophilic

describes a substance or structure attracted to water

hydrophobic

describes a substance or structure repelled by water

hypertonic

describes a solution concentration that is higher than a reference concentration

hypotonic

describes a solution concentration that is lower than a reference concentration

integral protein

membrane-associated protein that spans the entire width of the lipid bilayer

intermediate filament

type of cytoskeletal filament made of keratin, characterized by an intermediate thickness, and playing a role in resisting cellular tension

interphase

entire life cycle of a cell, excluding mitosis

interstitial fluid (IF)

fluid in the small spaces between cells not contained within blood vessels

intracellular fluid (ICF)

fluid in the cytosol of cells

isotonic

describes a solution concentration that is the same as a reference concentration

kinetochore

region of a centromere where microtubules attach to a pair of sister chromatids

lysosome

membrane-bound cellular organelle originating from the Golgi apparatus and containing digestive enzymes

messenger RNA (mRNA)

nucleotide molecule that serves as an intermediate in the genetic code between DNA and protein

metaphase

second stage of mitosis (and meiosis), characterized by the linear alignment of sister chromatids in the center of the cell

metaphase plate

linear alignment of sister chromatids in the center of the cell, which takes place during metaphase

microfilament

the thinnest of the cytoskeletal filaments; composed of actin subunits that function in muscle contraction and cellular structural support

microtubule

the thickest of the cytoskeletal filaments, composed of tubulin subunits that function in cellular movement and structural support

mitochondrion

one of the cellular organelles bound by a double lipid bilayer that function primarily in the production of cellular energy (ATP)

mitosis

division of genetic material, during which the cell nucleus breaks down and two new, fully functional, nuclei are formed

mitotic spindle

network of microtubules, originating from centrioles, that arranges and pulls apart chromosomes during mitosis

mutation

change in the nucleotide sequence in a gene within a cell’s DNA

nuclear envelope

membrane that surrounds the nucleus; consisting of a double lipid-bilayer

nuclear pore

one of the small, protein-lined openings found scattered throughout the nuclear envelope

nucleolus

small region of the nucleus that functions in ribosome synthesis

nucleus

cell’s central organelle; contains the cell’s DNA

organelle

any of several different types of membrane-enclosed specialized structures in the cell that perform specific functions for the cell

osmosis

diffusion of water molecules down their concentration gradient across a selectively permeable membrane

oxidative stress

a phenomenon caused by an imbalance between production and accumulation of oxygen reactive species (ROS) in cells

passive transport

form of transport across the cell membrane that does not require input of cellular energy

peripheral protein

membrane-associated protein that does not span the width of the lipid bilayer, but is attached peripherally to integral proteins, membrane lipids, or other components of the membrane

peroxisome

membrane-bound organelle that contains enzymes primarily responsible for detoxifying harmful substances

phagocytosis

endocytosis of large particles

phospholipid bilayer

membrane made out of two layers of phospholipids

pinocytosis

endocytosis of fluid

plasma membrane

See definition for cell membrane

polypeptide

chain of amino acids linked by peptide bonds

promoter

region of DNA that signals transcription to begin at that site within the gene

prometaphase

the phase of mitosis following prophase and preceding metaphase, characterized by disappearance of nuclear envelop and the appearance of mitotic spindle and kinetochores at the centromeres. 

prophase

first stage of mitosis (and meiosis), characterized by breakdown of the nuclear envelope and condensing of the chromatin to form chromosomes

proteasomes

Nonmembranous organelle that recycle faulty proteins

proteome

full complement of proteins produced by a cell (determined by the cell’s specific gene expression)

reactive oxygen species (ROS)

a group of extremely reactive peroxides and oxygen-containing radicals that may contribute to cellular damage

receptor

protein molecule that contains a binding site for another specific molecule (called a ligand)

receptor-mediated endocytosis

endocytosis of ligands attached to membrane-bound receptors

ribosome

cellular organelle that functions in protein synthesis

Rough ER (RER)

Endoplasmic reticulum with its membrane dotted with ribosomes

RNA polymerase

enzyme that unwinds DNA and then adds new nucleotides to a growing strand of RNA for the transcription phase of protein synthesis

S phase

stage of the cell cycle during which DNA replication occurs

selective permeability

feature of any barrier that allows certain substances to cross but excludes others

sister chromatid

one of a pair of identical chromosomes, formed during DNA replication

sodium-potassium pump

(also, Na+/K+ ATP-ase) membrane-embedded protein pump that uses ATP to move Na+ out of a cell and K+ into the cell

smooth ER (SER)

Endoplasmic reticulum without ribosomes associated with its membrane

spliceosome

complex of enzymes that serves to splice out the introns of a pre-mRNA transcript

splicing

the process of modifying a pre-mRNA transcript by removing certain, typically non-coding, regions

telophase

final stage of mitosis (and meiosis), preceding cytokinesis, characterized by the formation of two new daughter nuclei

transcription

process of producing an mRNA molecule that is complementary to a particular gene of DNA

transfer RNA (tRNA)

molecules of RNA that serve to bring amino acids to a growing polypeptide strand and properly place them into the sequence

translation

process of producing a protein from the nucleotide sequence code of an mRNA transcript

tubulin

protein that polymerizes into long chains or filaments that form microtubules

vesicle

membrane-bound structure that contains materials within or outside of the cell