Metabolism: Cellular Respiration

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.

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 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.

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, 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.

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.

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).

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.

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.

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.

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