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The Effect of Thiamine Treatment on the Activity of Pyruvate Dehydrogenase: Relation to the Treatment of Leigh's Encephalomyelopathy

1973; Springer Nature; Volume: 7; Issue: 7 Linguagem: Inglês

10.1203/00006450-197307000-00003

1530-0447

F.A. Hommes, Ruud Berger, G Luit-De-Haan,

Biochemical Acid Research Studies

Extract: Rats received intraperitoneal injection of thiamine (125 mg/kg body wt) for 4 consecutive days. There was less inhibition by ATP (9% ± 2%) of the pyruvate dehydrogenase complex of isolated liver mitochondria from treated rats than in liver mitochondria from control rats (30% ± 8%). The liver mitochondria of the treated animals contained about 25% more thiamine pyrophosphate than the mitochondria of the controls (0.48 ± 0.03 and 0.36 ± 0.01 nmoles/mg mitochondrial protein, respectively). Roche and Reed have demonstrated inhibition of the phosphorylation of the pyruvate dehydrogenase complex by thiamine pyrophosphate, thereby maintaining pyruvate dehydrogenase in the active form. It is suggested that the therapeutic effect of high doses of thiamine given to patients who suffer from Leigh's disease is, at least in part, due to maintainance of the pyruvate dehydrogenase complex in its active form, thus facilitating the oxidation of pyruvate. Speculation: Administration of high doses of thiamine to patients suffering from subacute necrotizing encephalomyelopathy seems to have a beneficial effect. Adverse effects, because of interference with a physiologic control mechanism, i.e., inhibition of the phosphorylation of the pyruvate dehydrogenase complex, may, however, interfere with its therapeutic value.