ExtractRats 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
The contribution to the glycolytic flux by glycogen breakdown versus glucose phosphorylation has been determined in isolated fetal rat hepatocytes, prepared in different media and subsequently incubated with different glucose concentrations. A high glucose concentration in cells prepared in a medium containing a high concentration of inorganic phosphate decreases the contribution to the glycolytic flux by glycogenolysis to less than 15%. It is suggested that one of the factors which initiate glycogenolysis in the living animal after birth is a lowered blood glucose concentration, independent of hormonal changes. Under conditions where glycogenolysis does not contribute the larger part to the glycolytic flux, the control of glycolysis is shifted from glycogen breakdown to the glucose phosphorylation step and phosphofructokinase.
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