Acyl-CoA dehydrogenase activity in the riboflavin-deficient rat. Effects of starvation.
Riboflavin deficiency in weanling rats causes a metabolic disorder characterized by failure to oxidize fatty acids. The disorder is similar to that seen in several human diseases, some of which are responsive to pharmacological doses of riboflavin. Previous analysis of the riboflavin-deficient rat has shown that the failure of fatty acid oxidation is due to a decrease in the activity of the acyl-CoA dehydrogenases of beta-oxidation. The activity of these flavoenzymes in liver rapidly decreases when a riboflavin-deficient diet is initiated. The objectives of these experiments were to analyse the effects of starvation on liver mitochondria isolated from the riboflavin-deficient rat. Our studies show that the decreased mitochondrial fatty acid oxidation induced by riboflavin deficiency is partially reversed by starvation. The extent of this reversal is proportional to the duration of starvation. The starvation-associated increase in fatty acid oxidation is mediated by an increase in the mitochondrial short-chain acyl-CoA dehydrogenase activity. The activity of this enzyme is increased such that the ratio of short-chain acyl-CoA dehydrogenase apoenzyme to holoenzyme does not change. We conclude that short-chain acyl-CoA dehydrogenase activity is limiting for fatty acid oxidation when its activity falls below a critical point. The increased mitochondrial specific activity of short-chain acyl-CoA dehydrogenase during starvation may result from an increased availability of flavin coenzyme or an increase in enzyme catalytic efficiency.
Ross
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Veterans Administration Hospital, Cleveland, OH.
Hoppel
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CL
D042964:Acyl-CoA Dehydrogenase; D044944:Acyl-CoA Dehydrogenases / Q000378:metabolism*; D000818:Animals; D044926:Butyryl-CoA Dehydrogenase; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology*; D010084:Oxidation-Reduction; D010172:Palmitoylcarnitine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012257:Riboflavin Deficiency / Q000201:enzymology*; D013217:Starvation / Q000201:enzymology
D010172:Palmitoylcarnitine; D044944:Acyl-CoA Dehydrogenases; D044926:Butyryl-CoA Dehydrogenase; D042964:Acyl-CoA Dehydrogenase; D002334:Carnitine O-Palmitoyltransferase; D002950:Citrate (si)-Synthase