Altered acyl-CoA metabolism in riboflavin deficiency.
We have recently described the effects of riboflavin deficiency on the metabolism of dicarboxylic acids (Draye et al. (1988) Eur. J. Biochem. 178, 183-189). As both mitochondria and peroxisomes are thought to be involved, we have examined the activities of various enzymes in these organelles in the livers of riboflavin-deficient rats. Mitochondrial beta-oxidation of fatty acids was severely depressed due to loss of activity of the three fatty acyl-CoA dehydrogenases, whereas there was an enhancement of peroxisomal beta-oxidation due to an increased activity of the FAD-dependent fatty acyl-CoA oxidase, although the activities of other peroxisomal flavoproteins, D-amino acid oxidase and glycolate oxidase, were lowered. Hepatocyte morphometry revealed an increase in the numbers of peroxisomes, indicating a proliferation induced by the deficiency. The mitochondrial acyl-CoA dehydrogenases involved in branched-chain amino acid metabolism were also severely decreased leading to characteristic organic acidurias. There was some loss of activity of the flavin-dependent sections of the electron transport chain (complexes I and II), but these were probably not sufficient to affect normal function in vivo. The specificity of these effects allows the use of the riboflavin-deficient rat as a model for the study of dicarboxylate metabolism.
Veitch
K
K
Laboratoire de Chimie Physiologique, I.C.P. & UCL, Brussels, Belgium.
Draye
J P
JP
Vamecq
J
J
Causey
A G
AG
Bartlett
K
K
Sherratt
H S
HS
Van Hoof
F
F
D000214:Acyl Coenzyme A / Q000378:metabolism*; D042962:Acyl-CoA Oxidase; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D002264:Carboxylic Acids / Q000652:urine; D003605:D-Amino-Acid Oxidase / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000494:pharmacology; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000648:ultrastructure*; D008297:Male; D008830:Microbodies / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology*; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012257:Riboflavin Deficiency / Q000201:enzymology*; D013385:Succinate Dehydrogenase / Q000378:metabolism
D000214:Acyl Coenzyme A; D002264:Carboxylic Acids; D005182:Flavin-Adenine Dinucleotide; D010088:Oxidoreductases; D000429:Alcohol Oxidoreductases; C020821:glycollate oxidase; D044943:Fatty Acid Desaturases; D042962:Acyl-CoA Oxidase; D013385:Succinate Dehydrogenase; D005969:Glutamate Dehydrogenase; D003605:D-Amino-Acid Oxidase