The metabolism of pyruvate

Pyruvate arising from glycolysis (or from amino acids; section 9.3.2) can be metabolized in three different ways, depending on the metabolic state of the body:

  • reduction to lactate (section 5.4.1.2);
  • as a substrate for gluconeogenesis (section 5.7);
  • complete oxidation to carbon dioxide and water (sections 5.4.3.1 and 5.4.4). 5.4.3.1 The oxidation of pyruvate to acetyl CoA

The first step in the complete oxidation of pyruvate is a complex reaction in which carbon dioxide is lost and the resulting two-carbon compound is oxidized to acetate. The oxidation involves the reduction of NAD+ to NADH. As 2 mol of pyruvate is formed from each mol of glucose, this step represents the formation of 2 mol of NADH,

COOH

icoA acetyl CoA

pyruvate hydroxethyl thiamin diphosphate

thiamin diphosphate

CHOH

pyruvate enzyme-bound thiamin diphosph icoA acetyl CoA

hydroxethyl thiamin diphosphate enzyme-bound thiamin diphosph

NADH

Figure 5.16 The reaction of pyruvate dehydrogenase.

equivalent to 6 X ATP for each mol of glucose metabolized. The acetate is released from the enzyme esterified to coenzyme A, as acetyl CoA (Figure 5.16). (Coenzyme A is derived from the vitamin pantothenic acid; section 11.13.1.1).

The decarboxylation and oxidation of pyruvate to form acetyl CoA requires the coenzyme thiamin diphosphate, which is formed from vitamin B (section 11.6.2). In thiamin deficiency, this reaction is impaired, and deficient subjects are unable to metabolize glucose normally. Especially after a test dose of glucose or moderate exercise they develop high blood concentrations of pyruvate and lactate. In some cases this may be severe enough to result in life-threatening acidosis.

Thiamin deficiency is not uncommon in alcoholics; apart from a low intake of the vitamin, alcohol inhibits the transport of thiamin from intestinal mucosal cells into the bloodstream. There is little storage of thiamin in the body, and deficiency can develop within a few weeks (see Problem 5.2).

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