Inhibition of beta-oxidation by 3-mercaptopropionic acid produces features of Reye's syndrome in perfused rat liver.
OBJECTIVE
The cause of Reye's syndrome has not been completely defined. The rate of ketogenesis in the liver is a key determinant of, and reciprocally related to, triglyceride secretion. In the present study, 3-mercaptopropionic acid (MPA), a known inhibitor of mitochondrial long-chain acyl coenzyme A (CoA) dehydrogenase, was used to investigate the relationship between ketone body production, triglyceride secretion, and triglyceride accumulation in perfused rat liver.


METHODS
Livers from fasted rats were perfused 225 minutes with or without MPA in the presence of [1-14C]oleic acid. Morphology was studied by light and electron microscopy.


RESULTS
Inhibition of fatty acid oxidation by the liver with MPA resulted in a decrease in ketone body production. Treatment with MPA caused an accumulation of small-droplet triglycerides in liver, whereas the net secretion of triglyceride ceased after an initial period of increased secretion with continued decreased ketogenesis. At the end of the perfusion period, mitochondria in the MPA group appeared to be damaged.


CONCLUSIONS
The rates of both ketogenesis and triglyceride secretion by the liver appear to be the major determinants of hepatic triglyceride content. In addition, the MPA-mediated biochemical and morphological findings are quite similar to those of Reye's syndrome.
Yamamoto
M
M
Department of Chemistry, Kurume University School of Medicine, Japan.
Nakamura
Y
Y
D015097:3-Mercaptopropionic Acid / Q000494:pharmacology*; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism; D007657:Ketone Bodies / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000473:pathology; D010084:Oxidation-Reduction; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012202:Reye Syndrome / Q000378:metabolism* / Q000473:pathology; D014280:Triglycerides / Q000378:metabolism
D005227:Fatty Acids; D007657:Ketone Bodies; D014280:Triglycerides; D015097:3-Mercaptopropionic Acid