Anaerobic pyruvate oxidation

Under aerobic conditions, pyruvate can be oxidatively decarboxylated via the pyruvate dehydrogenase multienzyme complex to yield acetyl-CoA, which can then be completely oxidised via the citric acid cycle (Fig. 2). In eubacteria growing anaerobically, pyruvate is metabolised fermentatively, thus serving as an electron sink for reducing equivalents generated in its formation from glucose. The diverse array of possible fermentative reactions from pyruvate is reviewed in [5]. 

Many other carboxylation reactions exist (Barton et al., 1991). For example, in methylo-trophic bacteria, formaldehyde and CO2 are combined to produce acetyl-CoA in the serine or hydroxypyruvate pathway. In contrast, the ribulose monophosphate cycle, which is another methylotrophic pathway of formaldehyde fixation, does not involve carboxylation steps. In addition to those described above, commonly found carboxylation reactions include those of pyruvate or phosphoenol pyruvate. In view of several relatively recent discoveries of novel CO2 assimilation pathways (e.g., the hydoxypro-pionate cycle and anaerobic ammonium oxidation) and growing interest in deep-subsurface microbiology, novel pathways of CO2 incorporation may be discovered in the near future. 

T A a BP /J a shift occurs from aerobic pyruvate oxidation to anaerobic production of lactate as the means for producing ATP. 

As an athlete s cells begin to go anaerobic, what happens to the rate of pyruvate oxidation by the citric acid cycle What happens to the rate of glycolysis Explain how each of these rate changes occurs and which enzymes are affected. 

Glycolysis, an anaerobic process, oxidizes glucose to yield a 3-carbon compound, pyruvic acid. Obviously, a large part of the chemical energy stored in the glucose molecule remains unavailable for cellular metabolism. Fortunately, there exists a biochemical device capable of oxidizing pyruvic acid to CO2 and water in the presence of oxygen. It is known as the Krebs cycle, the tricarboxylic acid cycle, or the citric acid cycle [69-73] (see Fig. 1-13). 

In Desulfovibrio, as in other strict anaerobes and some aerobic microorganisms, pyruvate is oxidatively decarboxylated by pyruvate oxidoreductase (FOR) according to the following reaction ... 

Glucose is metabolized to pyruvate by the pathway of glycolysis, which can occur anaerobically (in the absence of oxygen), when the end product is lactate. Aerobic tissues metabolize pyruvate to acetyl-CoA, which can enter the citric acid cycle for complete oxidation to CO2 and HjO, linked to the formation of ATP in the process of oxidative phosphorylation (Figure 16-2). Glucose is the major fuel of most tissues. 

Lactate is the end product of glycolysis under anaerobic conditions (eg, in exercising muscle) or when the metabolic machinery is absent for the further oxidation of pyruvate (eg, in erythrocytes). 

Mitochondria from body wall muscle and probably the pharynx lack a functional TCA cycle and their novel anaerobic pathways rely on reduced organic acids as terminal electron acceptors, instead of oxygen (Saz, 1971 Ma et al, 1993 Duran et al, 1998). Malate and pyruvate are oxidized intramitochondrially by malic enzyme and the pyruvate dehydrogenase complex, respectively, and excess reducing power in the form of NADH drives Complex II and [3-oxidation in the direction opposite to that observed in aerobic organelles (Kita, 1992 Duran et al, 1993 Ma et al,... 

Similarly, the regulation of PDK activity is modified in adult muscle PDC. For example, PDK activity is inhibited by pyruvate and propionate (metabolites elevated during anaerobic metabolism) and is less sensitive to stimulation by elevated NADH/NAD+ and acetyl CoA/CoA ratios (Fig. 14.2) (Thissen et al, 1986 Chen et al, 1998). The effects of NADH and acetyl CoA on PDK activity are mediated by the degree of E3-catalysed oxidation and E2-catalysed acetylation of the inner lipoyl domain of E2 (Roche and Cate, 1977 Rahmatullah and Roche, 1985, 1987 Ravindran et al, 1996 Yang et al, 1998), so that the regulation of this phenomenon is complex and involves multiple interacting components. 

The realization of the widespread occurrence of amino acid radicals in enzyme catalysis is recent and has been documented in several reviews (52-61). Among the catalytically essential redox-active amino acids glycyl [e.g., anaerobic class III ribonucleotide reductase (62) and pyruvate formate lyase (63-65)], tryptophanyl [e.g., cytochrome peroxidase (66-68)], cysteinyl [class I and II ribonucleotide reductase (60)], tyrosyl [e.g., class I ribonucleotide reductase (69-71), photosystem II (72, 73), prostaglandin H synthase (74-78)], and modified tyrosyl [e.g., cytochrome c oxidase (79, 80), galactose oxidase (81), glyoxal oxidase (82)] are the most prevalent. The redox potentials of these protein residues are well within the realm of those achievable by biological oxidants. These redox enzymes have emerged as a distinct class of proteins of considerable interest and research activity. 

When his studies on carbohydrate oxidation restarted in Sheffield, Krebs experiments included studies on the anaerobic dismutation of pyruvate by bacteria and various animal tissues. Assuming the role for the dicarboxylic acids postulated by Szent-Gyorgi, the main question was the route by which the carbon atoms of pyruvate were converted to succinate. In May 1936 Krebs had observed that if 2-oxoglutarate was added to pyruvate, the yield of succinate was enormously increased. In his notebook written that year (Holmes, 1993) Krebs postulated ... 

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