Cells: Structures and Processes

  1. Patterns that relate to all cells
    1. All cells face common problems. Cellular function is related to cellular structure. The ability to relate structure and function shows the common set of problems and selective pressures that organisms of all types must deal with. Unity of life functions and structures is evident amongst life's diversity.
    2. Each cell's specialization is related to its shape, size, and organelles.
    3. The life of a cell depends on the organizational pattern and development of its parts and their integrated activities.
    4. Linnaeus was one of the first to recognize that patterns of structure and development indicated rela tionships between groups of organisms.
    5. The development of the electron microscope and the ultracentrifuge enabled biologists and chemists to see patterns within the structure and chemistry of cells and thus to develop generalizations regarding the relationships between and among cells and organisms.
    6. Chemists discovered that the chemistry of living organisms did not differ in principle from the chemistry of the inorganic world. As Pasteur recognized, Biochemistry was thus a complex and fascinating branch of chemistry as applied to living systems.

  2. Fundamental features of cellular organization
    1. Compartmentalization - a property which allows the "effective" size of an object to increase without unduly affecting the surface area to volume relationship (S2V3)
      1. allows for increased surface area by subdividing sections of the cell
      2. limits certain cell constituents to certain parts of cell (destructive hydrolytic enzymes)
      3. makes it possible to concentrate substances in specific regions where specialized biochemical activities can occur
    2. Self Assembly - spontaneous arrangement of molecules into specific structures; requires no additional energy input and is often the result of chemical bonding; e.g. phospholipids into bilayers in mem- branes; proteins into tubules and filaments
    3. Repitition - cells from pre-existing cells; thus patterns of cellular organization are repeated from one generation to another
    4. An Inherent Genetic Program - embodied in cell's DNA each gene represents a segment of a DNA strand: DNA--->RNA--->polypeptides (proteins) is usual sequence; The program of an organism represents a plan for action - a blueprint which provides a set of instructions to be used under specific circumstances, in a sequence that may be triggered by the operation of the program itself
    5. Redundancy - represented by multiple copies of mole- cules' (e.g. enzymes); multiple copies of the genetic information; All body cells of the organism contain identical genetic information. Given the correct chemical signals and environmental conditions, the cell is capable of differentiation in several possible directions.

    Interesting concept map for studying cells.

  3. Early forms of microscopes were developed in 16th and 17th century Europe. Robert Hooke looked at cork and gave us the name "cells" as a result of his view of the structures. Other scientists developed a series of generalizations that came to be known as the Cell Theory. They concluded that all living things are made of cells and that living cells arise only from preexisting cells. Curious (and eccentric) non scientists like Anton von Leeuwenhoek made important contributions.

  4. The most fundamental differences in the living world are differences between prokaryotic and eukaryotic cells. These two types of cellular organization are found within the three Domains, or general categories of living things.
    1. The Kingdom Monera includes prokaryotes.
      1. Prokaryotes lack a membrane-bound nucleus; the chromosome is a naked strand of circular, double stranded DNA. It is localized in a region called the nucleoid.
      2. Prokaryotes lack other membrane-bound ORGANELLES.
    2. The other four kingdoms, Protista, Fungi, Plantae, and Animalia, are eukaryotic.
      1. Like prokaryotes, eukaryotic cells are surrounded by a CELL MEMBRANE.
      2. Eukaryotic cells have internal membranes that surround the nucleus and other internal structures.
      3. Eukaryotes have a highly organized CYTOPLASM with an internal latticework, the CYTOSKELETON, that contri butes to structure and movement within the cell.
      4. In multicellular eukaryotes, cells may specialize for given tasks.
      5. Common features of plant and animal cells include a NUCLEUS, MITOCHONDRIA, RIBOSOMES, ENDOPLASMIC RETIC ULUM, GOLGI BODIES, MICROTUBULES, MICROFILAMENTS, and a PLASMA OR CELL MEMBRANE.
        1. Plant cells may be surrounded by a CELL WALL and may be largely filled by a storage organelle, the VACUOLE.
        2. Plant cells may contain CHLOROPLASTS, which carry out photosynthesis.
        3. Cellular specialization ultimately led to specialization of tissues, organs, and systems within multicelled organisms.

  5. Cells vary in size and number in organisms
    1. Most cells are small. Prokaryotes are the smallest cells. The largest animal cells include ostrich eggs and giraffe nerve cells.
    2. The surface-to-volume ratio (S/V) determines a cell's ability to exchange materials with its environment. A cell's shape affects it S/V.

  6. All cells must perform certain tasks.
    1. The cytoplasm must be separated from its environment so appropriate homeostatic internal conditions can be maintained.
    2. The cell must take in raw materials and expel wastes through the membrane and other barriers that may separate it from its environment.
    3. It must take in energy and convert it to a form useful for powering the cellular machinery.
    4. It must synthesize molecules and cell parts for repair growth and replacement (reproduction).
    5. It must coordinate and regulate its activities.

  7. All eukaryotic cells have certain structures.
    1. The PLASMA OR CELL MEMBRANE separates the cell from its environment and controls the movement of substances into and out of the cell.
      1. The membrane is a LIPID BILAYER composed of PHOSPHO LIPID molecules with hydrophilic heads and hydro phobic tails. It is SEMIPERMEABLE.
      2. The membrane includes proteins that stabilize the lipid bilayer and act as gates, pumps, markers, or signal receptors.
      3. The membrane may fold inward to import materials (endocytosis) or outward to expel materials from the cell (exocytosis).
    2. The NUCLEUS is the largest organelle and contains the genetic material, DNA.
      1. The genetic information passes from DNA to RNA to proteins, which carry out the work of the cell.
      2. The NUCLEOPLASM of the nucleus is surrounded by a double-layer membrane, the NUCLEAR ENVELOPE OR MEMBRANE, which is perforated by pores. Each pore is a cluster of proteins that form a channel. Flow of molecules between the interior of the nucleus and the cytoplasm is regulated by a protein called Ran which directs molecular traffic.(Science, Vol. 279, February 20, 1998, p.1129-1131.)
      3. RIBOSOMAL RNA is formed on the ends of certain chromosomes and thus creates the dark-stained regions known as NUCLEOLI. After being exported to the cytoplasm, this RNA forms RIBOSOMES, which build protein according to the genetic blueprints encoded in messenger RNA.
    3. The CYTOSKELETON is a 3-dimensional latticework composed of proteins which are arranged into MICROFILAMENTS,MICROTUBULES, and INTERMEDIATE FILAMENTS that maintain the cell's shape and move materials within the cell.
    4. A system of INTERNAL MEMBRANES is involved in the manufacture, storage, transport, and export of proteins and raw materials.
      1. The ENDOPLASMIC RETICULUM (ER) is a series of membrane channels that may be studded on the outside with ribosomes (rough ER) for protein synthesis or without ribosomes (smooth ER) and involved in the synthesis of non-proteins such as lipids.
      2. After proteins are constructed on the ribosomes they come into contact with the ER and a channel is formed to allow entrance of these proteins into the ER. Once the protein has entered, a portion of one end (the signal portion) is enzymatically removed. The channel is disassembled.(Hanein, D., Matlack, K.E.S., Jingmikel, B., Plath, K., Kalies, K-U, Miller, K.R., Rapoport, T.A., and Akey, C.W. "Oligomeric rings of the Sec61p complex induced by ligands required for protein transloation."Cell,87. 721-732, November 5, 1996.)
      3. At the ends of the ER channels, membrane sacs (vesicles) pinch off and carry the products to their destination, which may be another membrane system, the GOLGI COMPLEX, which sorts, modifies and packages proteins, lipids, and other substances and exports most of them from the cell. (See also Science, "Coming to Grips with the Golgi," Vol. 282, December 18, 1998, p. 2172-2174.)
      4. LYSOSOMES contain digestive enzymes that break down ingested food or, if broken open, digest the cellular components. The acidic pH requirement of the enzymes of the lysosome prevents immediate damage to the cell if the contents were to enter the cytosolic compartment.
    5. MITOCHONDRIA provide chemical fuel for cellular processes by converting the energy in carbon-containing molecules into the energy of ATP molecules. This process is called AEROBIC RESPIRATION when oxygen is present in adequate supplies for the cell. Additional information will be found in WebUnit 8. Mitochondria and Chloroplasts have a prokaryotic origin and represent an example of endosymbiosis. Each have their own DNA and ribosomes and are capable of semiautonomous growth and reproduction. (See also Scientific American, "Mitochondrial DNA in Aging and Disease," August 1997, p. 40-47.)
    6. Organelles of movement are made of protein and include CILIA, FLAGELLA, and microfilaments and microtubules.
      1. Cilia and flagella have the same internal structure, with 9 pairs of microtubules in a circle surrounding 2 inner microtubules.
      2. Using ATP energy, the microtubules slide past one another, causing the structure to bend.
    7. The plasma membranes of most cells are surrounded by cell coverings that protect the delicate membrane.
      1. An EXTRACELLULAR MATRIX, a meshwork of secreted molecules, protects many cells that live within multicellular organisms.
      2. CELL WALLS are made largely of cellulose and surround plant cells.
      3. Virtually all animal cells secrete a meshwork of molecules that surrounds them. These molecules are mostly fibrous proteins. COLLAGEN is the most common of the fibrous proteins.

Transport Mechanisms
  1. Cells require and use energy and materials to perform cellular tasks. Such task might include movement, packaging and exporting materials, dividing and reproducing. As energy flows within a cell these materials also flow so that growth, repair and replacement may continue within the cell. These materials move in the INTRACELLULAR FLUID (the fluid within the cells).
    1. Cells of multicellular organisms are surrounded by EXTRACELLULAR FLUID (fluid outside of the cell). Single-cell organisms are surrounded by the water in which they live or in the fluids of their host's body.
    2. Materials move through membranes and within cells by PASSIVE TRANSPORT mechanisms such as DIFFUSION or OSMOSIS. In passive transport, the cells do not use any energy to move the molecules. The molecules move through a gradual change or GRADIENT. Materials may also move through membranes by ACTIVE TRANSPORT MECHANISMS. Here the cell uses energy to get molecules into or out of the cell against the gradient. Active transport is a little bit like going the wrong way on a one way street.
    3. DIFFUSION is the tendency of molecules or materials to move from areas of high concentrations into areas the same molecules are in a lower concentration. Most materials move by simple diffusion through the semi permeable membrane surrounding the cell. A semi permeable membrane only allows certain types of molecules to enter or leave the cell. Limitations may be based on sized or charge of the molecules.
    4. OSMOSIS is the movement of a solvent such as water through a semipermeable membrane from areas of high concentration to areas of low concentration of the same solvent. In cells the solvent is water.
    5. In HYPOTONIC solutions, water moves into the cell; in ISOTONIC solutions, the water entering and leaving is about equal and so there is no net movement; in HYPERTONIC solutions, water moves out of a cell. Plant cells have higher solute concentrations (and thus lower solvent concentrations) than the surrounding fluids. This leads to a movement of solvent (water) molecules into the cell and causes an increase in the pressure inside of the cell. This pressure is called TURGOR PRESSURE and helps to keep the cells rigid or stiff.
    6. In FACILITATED DIFFUSION transport proteins in the membrane help move molecules along the concentration gradient without any additional energy input by the cell.
    7. Certain molecules in the membrane, mostly proteins, act like pumps using energy to move materials against concentration gradients.
      1. The sodium-potassium pump moves K + into the cell and Na + out.
      2. Other membrane pumps move glucose, amino acids and other raw materials into the cell.
  2. Cells communicate through connections
    1. Multicellular organisms have cellular connections of various types. Four types are common. Desmosomes,found in the skin, are localized patches that hold skin together while allowing flexibility. Also included are the Adherens, such as cadherins found in the small intestine, Tight Junctions to provide watertight seals in areas like the bladder, and Gap Junctions to allow passage of molecules such as in the liver. All of these are found in animal cells.
    2. Plants have Plasmodesmata to create continuous cytoplasmic connections between adjacent cells to move water, nutrients and hormones.

Membrane Structure: How it Relates to Function

Over the last thirty five years, our concept of the plasma membrane has changed considerably from the simple three-layered structure surrounding the cell to that of a FLUID MOSAIC MODEL. This model of the membrane consists of a fluid phospholipid bilayer with a mosaic of interspersed proteins embedded in the lipid layers. Some proteins extend through both lipid layers, while others may extend only halfway or be loosely bound to the surface of the membrane. Chemical analysis of several kinds of membranes reveals that most contain about 50 percent protein and 50 percent lipid. Membrane surrounding cytoplasmic organelles or specialized cells may have percentages that vary from this 1:1 ratio. The inner membranes of the mitochondria, for example, contain 75 percent protein and only 25 percent lipid. Membranes of nerve cells often contain 90 percent lipid and 10 percent protein. The fluid mosaic model explains many of the known facts about membrane functions, but much remains unknown about both its structure and its interactions with the kinetic activity of ions and molecules in order to sustain the necessary conditions for the living cell (1).

ARCHITECTURE OF THE PLASMA MEMBRANE (2)

Cell membranes are assembled from four components:

1. A lipid bilayer foundation - every cell membrane has as its basic foundation a phospholipid bilayer. The lipid bilayer is a fluid like the "shell" of a soap bubble. It has the viscosity of olive oil. The other components of the membrane are enmeshed within the bilayer, which provides a flexible matrix and, at the same time, imposes a barrier to permeability. Within the lipid bilayer of animal cells, cholesterol molecules are inserted, adding fluidity.

2. Transmembrane proteins - a major component of every membrane is a collection of proteins that float within the lipid bilayer like icebergs on the sea. These proteins provide channels into the cell through which molecules and information pass. Membrane proteins are not fixed in position like headstones in a graveyard. Instead, they move about like boats on a lake. Some membranes are crowded with proteins, side by side, just as some lakes are so crowded with boats you can hardly see the water. In other membranes, the proteins are more sparsely dispersed. The nonpolar regions of the proteins serve to tie them to the membrane's nonpolar interior. The three principal classes of membrane protein are CHANNELS, RECEPTORS, and CELL SURFACE MARKERS.

3. Network of supporting fibers - membranes are structurally supported by proteins that reinforce the membrane's shape. This is why a red blood cell is shaped like a doughnut rather than being irregular. The membrane is held in that shape by a scaffold of protein on its inner surface. Membranes use networks of other proteins to control the lateral movements of some key membrane proteins, anchoring them to specific sites so that they do not simply drift away. Unanchored proteins have been observed to move as much as 10 micrometers in one minute.

4. Exterior glycolipids - a thicket of carbohydrate and lipid extends from the cell surface. These chains acts as cell identity markers. Different cell types exhibit different kinds of carbohydrate chains on their surfaces. Carbohydrate chains (strings of sugar molecules) are often bound to the proteins in the membrane. These chains, as mentioned, serve as distinctive identification tags, unique to particular types of cells.

A membrane, then, is a sheet of lipid and protein that is supported by other proteins and to which carbohydrates are attached. The key functional proteins acts as passages through the membrane, extending all the way across the bilayer. How do these transmembrane proteins manage to span the membrane, rather than just floating on the surface, in the way that a drop of water floats on oil? The part of the membrane that traverses the lipid bilayer is specially constructed, a spiral helix of nonpolar amino acids. Because water responds to nonpolar amino acids much as it does to nonpolar lipid chains, the nonpolar helical spiral is held within the interior of the lipid bilayer by the strong tendency of water to avoid contact with these amino acids. Although the polar ends of the protein protrude from both sides of the membrane, the protein itself is locked into the membrane by its nonpolar helical segment.

SOME WAYS A CELL'S MEMBRANES REGULATE ITS INTERACTIONS

WITH THE ENVIRONMENT (2)

1. Passage of water - membranes are freely permeable to water, but the spontaneous movement of water into and out of cells sometimes presents problems

2. Passage of bulk materials - cells sometimes engulf large hunks of other cells or gulp liquids

3. Selective transport of molecules - membranes are very picky about which molecules they allow to enter or leave the cell

4. Reception of information - membranes can identify chemical messages with exquisite sensitivity

5. Expression of cell identity - membranes carry name tags that tell other cells who they are

6. Physical connection with other cells - in forming tissues, membranes make special connections with each other

The movement of substances between cells and the surrounding environment occurs in three general ways: DIFFUSION, TRANSPORT BY PROTEIN CARRIERS, and ENDOCYTOSIS or EXOCYTOSIS. The movement of substances by diffusion does not require the input of cellular energy. The difference between active and passive (facilitated) transport by protein carriers may be distinguished on the basis of energy expenditure by the cell. Both endocytosis and exocytosis require energy and the formation of vacuoles.

MOVEMENT BY DIFFUSION

The establishment of a CONCENTRATION GRADIENT due to a higher concentration of molecules results in a diffusion of molecules into the cell. Movements through the membrane components depends on the size and chemical nature of the molecule. Oxygen, carbon dioxide, and other lipid soluble molecules, such as alcohol and benzene pass through the lipid portion of the thin 7.5 nm membrane (about 25X the thickness of a water molecule.) Water and other small ions are thought by some investigators to pass through protein - lined "pores." Small electrically charged ions would not be permitted such passage if these protein pores had a positive charge similar to the membrane itself. The positive ions would be repelled and negative ions would at first be attracted but then held at the surface (1).

TRANSPORT BY PROTEIN CARRIERS

The fact that some small molecules pass with ease, while others pass through with difficulty or not at all, has resulted in the membrane being regarded as SELECTIVELY PERMEABLE. When various sugars of identical molecular size are present both outside and inside the cell, certain ones cross the membrane hundreds of times faster than others. Observations also show that sugars and amino acids are able to diffuse through the membranes of cells that have been metabolically suppressed. This and other evidence indicates that the passage of these molecules is facilitated by a protein carrier without the expenditure of cellular energy. These carriers are thought to be highly specific and able to combine with only certain molecules. This FACILITATED DIFFUSION, assisted by protein carriers, operates under the same basic rules as does simple diffusion. Substances move only from an area of higher concentration to an area of lower concentration.

In contrast to facilitated diffusion, ACTIVE TRANSPORT requires the use of ATP energy by a carrier protein in order to move ions or molecules through the cell membrane against a concentration gradient. The molecules thus accumulate inside or outside a cell in a region of higher concentration. This process is considered to be responsible for the accumulation of an excess amount of solute within the cells. One example is an increase in the potassium ion concentration on the inside of the cell membrane (a thousand times greater than on the outside of the cell membrane). Other examples include the high concentration of iodine in the cells of the thyroid gland, the virtual removal of sodium from urine by cells lining the kidney tubules, and the total absorption of sugar by intestinal cell of the gut.

Subjecting cells to an increased ion concentration results in an increase in ion uptake, but only up to a point. Raising the concentration above a certain point does not increase the uptake. Graphically, the results of such experiments produce a saturation curve similar to the activity of an enzyme. The manner in which ions seemingly compete for a carrier suggests to some investigators a situation analogous to an enzyme-substrate complex. When a variety of similar ions, such as potassium, rubidium, and cesium are presented to the cell, the uptake of any ion in the group is slower than when the ion is alone. The same is true of calcium, strontium and barium. Interestingly, other close chemical relatives show no competition. Sodium, although similar to cesium, rubidium, and potassium, does not compete with these ions during uptake. The fact that active transport across a membrane can be thought of as an enzymatic activity has prompted some to give the protein carriers an enzymatic name - PERMEASES.

The energy used by the protein carriers might be necessary for the attachment of the molecule or ion, to change the shape of the carrier, to release the molecule, or a combination of all three. The expended energy results in the passage of the ion across the membrane. This renders the carrier useless for active transport until a high energy phosphate molecule is provided by another molecule of ATP. It is not surprising, therefore, that cells involved primarily with active transport, such as those of the kidney, have a large number of mitochondria near the surface membrane where active transport is occurring.

One type of active transport found in all cells, but especially important in muscle and nerve cells, involves the accumulation of sodium ions outside the cell and a corresponding accumulation of potassium ions within the cells. Since these two events are linked together, they are usually referred to as the sodium-potassium pump. The "pump" is thought to be a protein molecule carrier capable of combining with both the sodium and potassium ions. The external portion of the carrier allows the potassium ions to enter the cell while the internal part of the carrier assists the sodium ion to exit the membrane. The protein making up this channel changes its configuration by using energy from ATP molecules. The enzyme ATPase breaks the bond holding the terminal phosphate group in the molecule, thus releasing the bond energy. More than one third of all the energy expended by a cell that is not actively dividing is used to actively transport (Na+) sodium and (K+) potassium ions. Recent clinical investigations indicate a correlation between obesity and low levels of ATPase. This condition could result in a low metabolic rate since the Na+/K+ exchange is estimated to account for 20-50 percent of the body's total heat production and consumes considerable calories.(1,2)

ENDOCYTOSIS AND SURFACE RECEPTORS (1,2)

Endocytosis, although not directly related to active transport, can be more adequately explained using the fluid-mosaic model. At various locations over the surface of the membrane, receptor molecules with irregular protrusions extend beyond the cell. (1) These receptors are specific for larger required molecules. These receptor molecules are capable of diffusing over the surface of the cell by moving among the lipid molecules making up the outer layer of the membrane. This receptor molecule may contact the required molecule and form a receptor-molecule complex.

In general, the glycoprotein receptors are responsible for "self" recognition and identified as the major histocompatibility complex (MHC) proteins. Likewise, glycolipids are the cell surface markers that differentiate the various organs and tissues of the vertebrate body. The markers on the surface of red blood cells that distinguish different blood types are glycolipids. Recent studies have revealed new functions for mammalian glyco-proteins and glycolipids. New glycosylation processes have been discovered which may regulate macromolecular transport across the nuclear pore and may play a role in regulating gene expression. Carbohydrates play a key role in HIV and influenza virus infectivity. In cancer research, carbohydrates are being examined as tumor markers, and for their role in tumor metastasis (3).

Information transmitted between cells is carried by compounds that are often impermeable to the cell membrane. These compounds bind to cell surface receptors. This binding activates reaction pathways that terminate in the release of a compound into the cytoplasm that carries the original information. These compounds are called second messengers and can act either directly or indirectly. Second messengers transmit information regulating a variety of physiological and biochemical processes, including cell growth (4).

As the receptor-molecule complex continues to move over the undulating, irregular membrane surface, it will eventually reach an indented, pit-like region. After moving into the pit-like region, a type of invagination occurs around the receptor-molecule complex with some of the membrane's lipid molecules forming a lipid sphere. It should be noted that this sphere has a hydrophobic tail ends oriented outward making it soluble within the membrane. This sphere can move across the membrane to the cytoplasmic side. Again, the mosaic model provides an explanation of the spreading of the lipid molecules on the inner membrane surface. This in turn allows either for the foreign molecule to be released into the cytoplasm or for the vesicle to pass into the cytoplasm and transfer the molecule into a specific cell organelle. The lipid molecules that make up this transporting vesicle again become part of the membrane structure after the required molecule is released from the receptor-molecule complex.This is sometimes called receptor-mediatied endocytosis.

In summary, the fluid mosaic membrane model appears to resemble a flexible, undulating lipid layer with randomly positioned protein molecules extending partially or completely through the bilayer. Most biologically important organic molecules are insoluble in the center of the bilayer and thus the barrier properties of the membrane. To pass through this nearly impermeable barrier, many compounds require the aid of ATP and a protein molecule acting in some role as a carrier.

CELLULAR RESPIRATION - Burning Our Sugars as Well as our Oil

Cellular respiration is the process by which food molecules react with oxygen and are broken down to carbon dioxide and water with a net gain of captured energy in the form of ATP molecules. Therefore, it is the conversion of CHEMICAL energy of ORGANIC molecules to METABOLICALLY USABLE energy within living cells. Most of the process occurs within MITOCHONDRIA in EUKARYOTIC cells. All organisms utilize the processes of cellular respiration to provide energy for cellular maintenance and for the production of starting materials for the biosynthesis of needed compounds.

Cellular respiration occurs 24 HOURS/DAY in all organisms. Respiration is sometimes called BIOLOGICAL OXIDATION and thus may be compared to BURNING. Although both are OXIDATION reactions, the manner in which the energy is RELEASED differs in the two processes. In both, the energy released is obtained from CHEMICAL BONDS. CARBON DIOXIDE may be a WASTE PRODUCT in both. In BURNING there is an UNCONTROLLED, rapid release of energy with accompanying HIGH TEMPERATURES, but in CELLULAR RESPIRATION energy is released in discrete amounts due to ENZYME CONTROL of the process. Cellular respiration is a series of ENZYMATIC REACTIONS, and biological combustion cannot take place ANY FASTER than the controlling enzymes will permit. In BURNING most of the energy is released in the form of HEAT and LIGHT, but in cellular respiration most of the energy is used to create NEW CHEMICAL BONDS and only a relatively small amount of heat energy is liberated (2nd Law of Thermodynamics).

Biological oxidation is NOT necessarily the direct action of oxygen on a substance. It may mean the REMOVAL OF some ELECTRONS resulting in the formation of HYDROGEN IONS (H+) which are passed along an assembly line of CARRIER MOLECULES. When the hydrogen ions and the electrons reach oxygen, they combine with it to form water.

[Oxidation - addition of oxygen or removal of electrons]

[Reduction - loss of hydrogen or addition of electrons]

All of the enzymes involved in these transfers and all of the carrier molecules are found in the mitochondria, some of them exclusively. Many of the reaction require a COENZYME which acts in concert with the enzyme. The mitochondria are also rich in coenzymes.

Concurrently with all these transfers and oxidations, another process is going on. The energy released by oxidations is not transformed into heat but into a form that can be used by the cells. Transformation consists of making energy-rich compounds of ADENOSINE TRIPHOSPHATE or ATP. Most of the energy required by the cell is provided in this way and most of it is found in the mitochondria. Some of the energy of ATP is used in the mitochondria but most of the ATP is immediately transferred to the cytoplasm to power the other activities of the cell.

The most common form of cellular respiration (AEROBIC) proceeds through three stages: GLYCOLYSIS, KREBS or CITRIC ACID CYCLE, and OXIDATIVE PHOSPHORYLATION (ELECTRON TRANSPORT CHAIN).

The cellular process used for the initial breakdown of 6-carbon sugars is called GLYCOLYSIS and occurs in the CYTOSOL of the cell. The first stage involves the breakdown of one glucose molecule (6 carbons) into two molecules of the 3-carbon sugar GLYCERALDEHYDE3PHOSPHATE (G3P) or PHOSPHOGLYCERALDEHYDE, commonly called PGAL. This reaction sequence requires the ENERGY OF ACTIVATION of two ATP molecules. In the second stage of glycolysis the PGAL is converted to another 3-carbon compound PYRUVATE or PYRUVIC ACID. This process is coupled to the formation of four molecules of ATP per molecule of glucose. This series of reactions results in a NET GAIN of TWO ATP molecules and two pairs of HYDROGEN ATOMS.

NET REACTION

C6H12O6 + 2 ATP ---------------> 2(C3H4O3) + 4 ATP + 4 H

After its formation in the cytosol, pyruvate is transferred into the mitochondria where it is ultimately metabolized to carbon dioxide and water. The COST of the TRANSFER across the mitochondrial membrane is 2 ATP molecules. The final breakdown is accomplished by a series of reactions known as the KREBS CITRIC ACID CYCLE. Before beginning the cycle, pyruvate is converted into a 2-carbon fragment, known as ACETYL, with loss of carbon dioxide and 2 hydrogen atoms. The ACETYL fragment is carried into the cycle by COENZYME A or CoA. Once inside the cycle the CoA releases the Acetyl and returns to pick up additional acetyl fragments.

Any organic molecule that contains bond energy can be used as a fuel in cellular respiration. The common stage for almost all fuel molecules is the 2-carbon acetyl. The manner in which the acetyl stage is reached differs for different types of fuels.

KREBS CITRIC ACID CYCLE

This regenerating cycle is composed of 4-, 5-, and 6-carbon ORGANIC ACIDS. Prior to entering the cycle, the 3-carbon pyruvate is DECARBOXYLATED (carbon is removed) to give a 2-carbon ACETATE fragment. This fragment is activated by combining with COENZYME A to become Acetyl Coenzyme A. The carbon is given off as CARBON DIOXIDE and can be used as one measure of the rate of cellular respiration. The acetate fragment combines with a 4-carbon molecule in the cycle (OXALOACETIC ACID) to form the 6-carbon CITRIC ACID. As the cycle proceeds, CO2 is given off to produce a 5-carbon organic acid which subsequently loses another CO2 to become a 4-carbon organic acid. After a series of conversions and oxidations, the original 4-carbon oxaloacetic acid molecule is regenerated and is ready to combine with another acetate fragment and the cycle begins again.

ELECTRON TRANSPORT

Electron transport, also sometimes called OXIDATIVE PHOSPHORYLATION, is the process by which electrons are passed from the oxidation of Krebs Cycle organic acids to a series of electron acceptors (NAD, FAD or FMN, coenzyme Q, Cytochrome B, Cytochrome C, Cytochrome A, and Cytochrome A3). In this chain reaction, energy is transferred from the electron transport chain during the coupling of Pi (inorganic phosphate) to ADP to form ATP. This addition of phosphate to a molecule is called PHOSPHORYLATION.

If a pair of electrons is passed along the entire length of the electron transport chain, ATP is made in 3 separate places. Finally, after the electrons have lost most of their energy, they are transferred to molecular oxygen to produce H2O. The consequences of electron transport are to synthesize ATP and deliver protons (H+) and electrons (-) to oxygen forming water. This is the only point at which oxygen is required by aerobic organisms.

Glycolysis

C6H12O6 + 2 ATP ------------> 4 ATP + 2(C3H4O3) + 4 H

Krebs Cycle

2(C3H4O3) + 6 H2O ----------> 6 CO2 + 20 H

Electron Transport Chain

24 H + 6 O2 ----------------> 12 H2O + 36 ATP

Net Reaction

C6H12O6 + 6 O2 -------------> 6 CO2 + 6 H2O + 38 ATP

The total net reaction is AN AVERAGE of 38 ATP in bacteria and 36 ATP in eukaryotic cells as the result of the loss of 2 ATP molecules to cross the mitochondrial membranes. Actual energy yield depends on the starting molecular type and the number of oxidation steps required to reach the anhydride (CO2) level. The more steps required, the more energy released.

ANAEROBIC RESPIRATION & FERMENTATION

The mechanism of electron transport and oxidative phosphorylation is basically the same in anaerobes as in aerobes with minor variations.

  1. The final electron acceptor is not oxygen but some other INORGANIC molecule, such as nitrate (NO3), sulfate (SO4), nitrite (NO2) or an ORGANIC molecule such as fumurate. When an ORGANIC molecule is the final hydrogen (electron) acceptor the process is called FERMENTATION (SEE BELOW).
  2. The terminal enzyme component in electron transport in anaerobes is not cytochrome oxidase but enzymes such as REDUCTASES that catalyze the reduction of nitrate to nitrite, sulfate to hydrogen sulfide, and nitrite to molecular nitrogen. One of the most frequently used inorganic electron acceptors is nitrate, whereas fumarate is a more common organic electron acceptor. The synthesis of terminal reductases is repressed and their activities inhibited by oxygen. This mechanism is especially important in bacteria (facultative anaerobes) that switch from anaerobic to aerobic growth when oxygen becomes available.
  3. Less energy is realized during electron transport under anaerobic conditions. The difference in the oxidation-reduction potential between the donor and acceptor is not sufficient to generate more than one or two ATP molecules.

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Glycolysis and Fermentation

The anaerobic breakdown of glucose is called GLYCOLYSIS or the EMBDEN-MEYERHOFF-PARNAS (EMP) PATHWAY. The final electron acceptors in glycolysis are two 3-carbon units, called PYRUVATE, which can be reduced to LACTATE and other products. Overall, the process of glycolysis results in the incomplete oxidation of glucose to two molecules of pyruvate, the formation of NADH, and the formation of four molecules of ATP.

Lack of oxygen is a reaction barrier of the same sort as cyanide poisoning or vitamin deficiency (inhibition) with a damming of H back to NAD and pyruvic acid. thus, under conditions of limited oxygen, pyruvic acid changes its role from a FUEL to the FINAL HYDROGEN ACCEPTOR. The end results of this process depend upon the organisms in question - generally in plants and fungi the end products are CO2 and ethyl alcohol; in animals CO2 and lactate. In animals, as this OXYGEN DEBT is paid off by increasing amounts of oxygen becoming available, the lactic acid is converted to glucose in the liver, transformed to glycogen in muscle and oxidized to pyruvic acid and CO2 and sent to the Krebs cycle to complete the aerobic process.

Fermentation, as indicated earlier, is a metabolic process that releases energy from a sugar or other organic molecule. It does not require oxygen or an electron transport system, and used an ORGANIC molecule as the final electron acceptor. During fermentation, electrons (hydrogen) are transferred from NADH2 to pyruvic acid, which is turned into various end products.