Muscle pyruvic oxidase

The pyruvic oxidase of heart muscle recently studied by Schweet et al is still another special case. In the absence of added CoA, the acetyl moiety is hydrolytically cleaved to acetate TPP is the only required cofactor for this reaction in the presence of CoA, the end product is acetyl-CoA. The disposition of the hydrogens in this reaction is not yet clearly indicated. It is reported that the enzyme is relatively free of pyridine nucleotides, as well as flavin derivatives. There is some evidence that H2O0 may be produced as a product of the reaction with oxygen. The authors reach the conclusions that their enzyme contains an auto-oxidizable electron carrier. 

Schweet et al have reported the partial purification of a soluble pyruvic oxidase from pigeon breast muscle that converts pyruvate to to acetate and CO2. The preparation contains flavin and protogen (pyruvate oxidation factor). Cocarboxylase and Mg++ are required for full activity. It is reported that CoA, DPN, or TPN are not required. 

Bound forms of POF do exist in nature and appear to be closely associated with enzymes involved in pyruvate metabolism. Korkes et although able to separate pyruvate dismutation into two enzymatic steps, were not able to remove POF from their enzymes. Schweet reported that pyruvic oxidase isolated from pigeon breast muscle, although homogenous in the ultracentrifuge, still contains POF activity. It is possible that these... 

Abnormalities of the respiratoiy chain. These are increasingly identified as the hallmark of mitochondrial diseases or mitochondrial encephalomyopathies [13]. They can be identified on the basis of polarographic studies showing differential impairment in the ability of isolated intact mitochondria to use different substrates. For example, defective respiration with NAD-dependent substrates, such as pyruvate and malate, but normal respiration with FAD-dependent substrates, such as succinate, suggests an isolated defect of complex I (Fig. 42-3). However, defective respiration with both types of substrates in the presence of normal cytochrome c oxidase activity, also termed complex IV, localizes the lesions to complex III (Fig. 42-3). Because frozen muscle is much more commonly available than fresh tissue, electron transport is usually measured through discrete portions of the respiratory chain. Thus, isolated defects of NADH-cytochrome c reductase, or NADH-coenzyme Q (CoQ) reductase suggest a problem within complex I, while a simultaneous defect of NADH and succinate-cytochrome c reductase activities points to a biochemical error in complex III (Fig. 42-3). Isolated defects of complex III can be confirmed by measuring reduced CoQ-cytochrome c reductase activity. 

In the primary oxidation of pyruvate, it is visualized that pyruvate reacts with cocarboxylase, giving a 2-carbon complex at the level of oxidation of acetaldehyde with the liberation of CO2. This is considered in greater detail in the section on cocarboxylase. The oxidase oxidizes this complex to an acetyl derivative which is not acetyl-CoA. The hypothetic acetyl derivative may subsequently undergo hydrolytic cleavage to free acetate or may be transferred to CoA, giving rise to acetyl-CoA. Korkes et have described a pyruvate dismutation reaction present in heart muscle which requires at least two enzymes, CoA and DPN. The initial reaction is presumed to yield, per mole of pyruvate, 1 mole each of acetyl-CoA, CO2, and reduced pyridine nucleotide. In this case the primary product appears to be acetyl-CoA. 

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