Overview Living organisms catabolize organic molecules within their cells and use the energy released to manufacture ATP by phosphorylating ADP. Many prokaryotes and virtually all eukaryotes phosphorylate ADP either through fermentation (anaerobic) or respiration (aerobic). Both of these processes involve oxidation of foodstuffs, yet only the latter requires oxygen. The Role of Coenzymes In metabolic pathways, coenzymes play a vital role. Metabolic enzymes operate in the body's cells and blood. Metabolic enzymes facilitate the chemical reactions that carry out the processes of metabolism. Typically, metabolic enzymes are composed of two components: (1) an "apoenzyme" that identifies which molecule within a cell requires a specific chemical reaction and (2) a "coenzyme" that initiates the specific chemical reaction. The body's primary sources of energy are produced at the cellular level by

metabolic processes. Coenzyme-A (CoA), Acetyl Coenzyme-A (acetyl CoA), Coenzyme Q10 (CoQ10) and Coenzyme 1 (NADH), together with certain B-vitamins and their coenzyme forms are necessary for such energy production during: (1) the tricarboxylic acid cycle (the TCA cycle, Krebs cycle, or citric acid cycle) and (2) the glycolitic cycle. Coenzyme-A is the most active metabolic enzyme in the human body. It operates in the body's cells and blood where it initiates hundreds of important processes in the body. Coenzyme-A passes out of the body and should be replenished on a daily basis. Coenzymes are chemicals synthesized by organisms from dietary vitamins. Coenzymes are carriers of substances to and from enzyme-catalyzed reactions: · NAD+ (oxidized form of nicotinamide adenine dinucleotide) carries hydrogen and is derived from dietary niacin. It is designated as NADH + H+ (sometimes NADH2) when it is in the reduced form. Recall that the reduced form is the energetically valuable one, whereas the oxidized form is the energy poor one. A structurally similar coenzyme, NADP+, is important in photosynthesis and other cellular phenomena. · FAD (oxidized form of flavin adenine dinucleotide) carries hydrogen and is derived from riboflavin. It is designated FADH2 when it is in the reduced form. · CoA (Coenzyme-A) carries an acetyl group to the site of the Krebs Cycle; it is derived from pantothenic acid. It may also carry a succinyl group. When combined, it is called acetyl (or succinyl) CoA. Glycolysis During glycolysis, the potential energy of a primary foodstuff, glucose, is released during a series of chemical reactions which occur in the cytoplasm. Some of the energy released when bonds are broken is used to phosphorylate ADP and some is transferred to a coenzyme, NAD+, which is reduced to NADH + H+. No oxygen is used during glycolysis. Pyruvate, a product of glycolysis may either be converted to lactate or ethanol (fermentation) or be converted to an acetyl group for further processing during the Krebs cycle. Fermentation Fermentation is a process whereby a cell can achieve redox balance (reoxidizing NADH + H+ which was produced in glycolysis), thus allowing for the oxidation of additional glucose during glycolysis. Two types of fermentation occur, one in yeast and one in muscle cells when oxygen is not available in adequate amounts to allow for oxidative phosphorylation. In the first process, the pyruvate resulting from glycolysis is converted to acetaldehyde then ethanol; in the second, the pyruvate is converted to lactic acid. Krebs Cycle (TCA Cycle or Citric Acid Cycle) If oxygen is available to support aerobic respiration, reactions occur subsequent to glycolysis within the mitochondrion (especially associated with the inner mitochondrial membrane). The first event to occur is oxidation of pyruvate to acetyl, which then combines with Coenzyme-A to yield acetyl CoA. Next, Coenzyme-A delivers the acetyl group to oxaloacetate (OXA), a four carbon compound already present in the mitochondrion, with which the 2 carbon acetyl group combines to form citric acid. This step initiates the "first turn" of the Krebs Cycle. At the end of the Krebs Cycle, oxaloacetate has once again been formed. A second acetyl CoA combines with it, initiating the second turn of the Krebs Cycle. After the second cycle has been completed, the original glucose has been turned into a total of 6 CO2 molecules yet no oxygen has been used. Only 4 ATP molecules have been netted. Oxidative Phosphorylation This process occurs on the plasma membrane of prokaryote cells and on the inner membrane of the mitochondrion; quantitatively, it is the most important way that ATP is made by aerobic cells. During the process, the coenzymes (NADH + H+ and FADH2) which have accumulated during previous processes transfer hydrogen atoms to components of the electron transport chain. During transport, hydrogens and electrons are transferred to acceptors in such a way that protons are pumped across the inner mitochondrial membrane. This results in an electrochemical gradient which is later used to phosphorylate ADP as protons diffuse back across the membrane. Hence, oxidative phosphorylation results from a process of chemiosmosis. In the final step of this sequence, electrons are transferred to oxygen and used in the formation of water. Energy Yield ATP molecules are made from the following: 2 from glycolysis, 2 from the Krebs cycle, 4 ATP from NADH + H+ during chemiosmosis from glycolysis, 6 from pyruvate oxidation, 18 from the Krebs cycle, 4 ATP from FADH2 during chemiosmosis from the Krebs cycle. TOTAL = 36 ATP molecules. In eukaryotic cells, the reduced NADH + H+ produced during glycolysis is actively transported into the mitochondrion, at a cost of 2 ATP molecules. Hence, the "energy yield" from that coenzyme is only 2 ATP molecules per NADH + H+, rather than 3 ATP molecules (as is the case for NADH + H+ produced within the mitochondrion). In prokaryotic cells, active transport into the mitochondrion does not occur, as chemiosmosis occurs at the plasma membrane. Hence, the energy yield for respiration in bacteria is 38 ATP molecules.