Effect of Acylcarnitines on Pyruvate Metabolism in Liver Mitochondria from Thiamin-deficient Rats

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Abstract
The effect of acylcarnitines on pyruvate metabolism was compared in liver mitochondria from thiamin-deficient and pair-fed rats. Respiration and oxidative phosphorylation were investigated with pyruvate, succinate, α-ketoglutarate or α-glycerophosphate as substrate. The respiratory rate was significantly decreased in state 4 when α-glycerophosphate was used as substrate (P < 0.001). In state 3, the respiratory rates in the presence of α-ketoglutarate, pyruvate or α-glycerophosphate were significantly decreased (P < 0.05). The ratio of ADP to oxygen was decreased when α-ketoglutarate was used as substrate (P < 0.025). Pyruvate utilization by liver mitochondria from thiamin-deficient rats was markedly decreased but the percentages of pyruvate carboxylation and oxidation were not altered. Acylcarnitines stimulated pyruvate carboxylation more in deficient mitochondria than in mitochondria from pair-fed controls. Maximum stimulation in the percentage carboxylation of pyruvate was obtained in the presence of 0.83 mML-octanoylcarnitine. Pyruvate oxidation was greatly reduced by the addition of acylcarnitines. These experiments indicate that the ability of fatty acids to alleviate the symptoms of thiamin deficiency may be related to their effect on the regulation of pyruvate carboxylase, a key enzyme in the pathway of gluconeogenesis.