Catabolism electron carriers

Nicotinamide is an essential part of two important coenzymes nicotinamide adenine dinucleotide (NAD ) and nicotinamide adenine dinucleotide phosphate (NADP ) (Figure 18.19). The reduced forms of these coenzymes are NADH and NADPH. The nieotinamide eoenzymes (also known as pyridine nucleotides) are electron carriers. They play vital roles in a variety of enzyme-catalyzed oxidation-reduction reactions. (NAD is an electron acceptor in oxidative (catabolic) pathways and NADPH is an electron donor in reductive (biosynthetic) pathways.) These reactions involve direct transfer of hydride anion either to NAD(P) or from NAD(P)H. The enzymes that facilitate such... 

Distinct coenzymes are required in biological systems because both catabolic and anabolic pathways may exist within a single compartment of a cell. The nicotinamide coenzymes catalyze direct hydride transfer (from NAD(P)H or to NAD(P)+) to or from a substrate or other cofactors active in oxidation-reduction pathways, thus acting as two-electron carriers. Chemical models have provided... 

Catabolism is the degradative phase of metabolism in which organic nutrient molecules (carbohydrates, fats, and proteins) are converted into smaller, simpler end products (such as lactic acid, C02, NH3). Catabolic pathways release energy, some of which is conserved in the formation of ATP and reduced electron carriers (NADH, NADPH, and FADH2) the rest is lost as heat. In anabolism, also called biosynthesis, small, simple precursors are built up into larger and more complex... 

The citric acid cycle (Krebs cycle, TCA cycle) is a nearly universal central catabolic pathway in which compounds derived from the breakdown of carbohydrates, fats, and proteins are oxidized to C02, with most of the energy of oxidation temporarily held in the electron carriers FADH2 and NADH. During aerobic metabolism, these electrons are transferred to 02 and the energy of electron flow is trapped as ATP. 

NAD-linked dehydrogenases remove two hydrogen atoms from their substrates. One of these is transferred as a hydride ion ( II ) to NAD+ the other is released as H+ in the medium (see Fig. 13-15). NADH and NADPH are water-soluble electron carriers that associate reversibly with dehydrogenases. NADH carries electrons from catabolic reactions to their point of entry into the respiratory chain, the NADH dehydrogenase complex described below. NADPH generally supplies electrons to anabolic reactions. Cells maintain separate pools of NADPH and NADH, with different redox potentials. This is accomplished by holding the ratios of [reduced form]/[oxidized form] relatively high for NADPH and relatively low for NADH. Neither NADH nor NADPH can cross the inner mitochondrial membrane, but the electrons they carry can be shuttled across indirectly, as we shall see. 

Comparing this equation with the equation for the complete oxidation of palmitoyl-CoA (see table 18.1, equation 1), we find major differences in carriers and intermediates. The principal electron carrier in the anabolic pathway is the NADPH-NADP+ system in the catabolic pathway, /3 oxidation, the principal electron carriers are FAD-FADH2 and NAD+-NADH. The second striking difference between the two pathways is that malonyl-CoA is the principal substrate in the anabolic pathway but plays no role in the catabolic pathway. These differences reflect the fact that the two pathways do not share common enzymes. Indeed, in animal cells the reactions occur in separate cell compartments biosynthesis takes place in the cytosol, whereas catabolism occurs in the mitochondria. 

Assay techniques GDH utilizes both nicotinamide nucleotide cofactors NAD+ in the direction of N liberation (catabolic) and NADP+ for N incorporation (assimilatory). In the forward reaction, GDH catalyzes the synthesis of amino acids from free ammonium and Qt-kg. The reverse reaction links amino acid metabolism with TCA cycle activity. In the reverse reaction, GDH provides an oxidizable carbon source used for the production of energy as weU as a reduced electron carrier, NADH, and production of NH4+. As for other enzymes, spectrophotmetric methods have been developed for measuring oxoglutarate and aminotransferase activities by assaying substrates and products of the GDH catalyzed reaction (Ahmad and Hellebust, 1989). 

FIGURE 19.1 The central relationship of the citric acid cycle to catabolism. Amino acids, fatty acids, and glucose can all produce acetyl-CoAin stage 1 of catabolism. In stage 2, acetyl-CoA enters the citric acid cycle. Stages 1 and 2 produce reduced electron carriers (shown here as e"). In stage 3, the electrons enter the electron transport chain, which then produces ATP. 

All organisms use the same pair of pyridine nucleotides as carrier molecules for hydrogen and electrons. Both of these molecules accept hydrogen and electrons in the redox reactions of catabolism and become reduced. The oxidative half-reactions of catabolism generally produce two H+ and two electrons. The nicotinamide ring can accept two electrons and one H+ and, since the second H+ is released into the solution, most redox reactions in biological systems take the form ... 

The NADH that is produced in the mitochondrion thus passes electrons to the electron transport chain. With the malate-aspartate shuttle, 2.5 moles of ATP are produced for each mole of cytosolic NADH rather than 1.5 moles of ATP in the glycerol-phosphate shutde, which uses FADHg as a carrier. The Biochemical Connections box on page 600 discusses some practical applications of our understanding of the catabolic pathways. 

During oxidation, hydrogen ions (protons) and electrons are removed from fuel molecules and transferred to one of a small number of special carrier molecules. The most abundant such molecule is nicotinamide adenine dinucleotide (NAD+). It forms an essential link between the oxidative part of catabolism and the generation of ATP. 

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