Metabolism of [U-14C]-4-hydroxybutyric acid to intermediates of the tricarboxylic acid cycle in extracts of rat liver and kidney mitochondria.
The metabolism of [U-14C]-4-hydroxybutyric acid (GHB) was investigated in sonicates of mitochondria of rat heart, kidney and liver. The conversion of this precursor to 14C-organic acids was monitored and quantified by sequential liquid-partition chromatography on hydrated columns of silicic acid using a concave-upward gradient of 2-methylbutan-2-ol in chloroform. Sonicates of liver and kidney mitochondria, but not heart, readily converted [U-14C]-GHB to 14C organic acids via a pathway of conversion to 14C-succinic acid, followed by further metabolism through the tricarboxylic acid cycle. This conversion was facilitated by exogenous NAD+ and NADP+. No evidence for the beta-oxidation of GHB was obtained in any of the mitochondrial sonicates. Studies with exogenous non-labelled succinic semialdehyde indicated that this compound was an intermediate in the conversion of GHB to succinic acid.
Department of Pediatrics, University of California, San Diego, La Jolla.
K M
KM
Gibson
W L
WL
Nyhan
D000818:Animals; D001711:Biotransformation; D002951:Citrates / Q000378:metabolism; D002952:Citric Acid Cycle; D006885:Hydroxybutyrates / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012978:Sodium Oxybate / Q000378:metabolism*; D013386:Succinates / Q000378:metabolism
D002951:Citrates; D006885:Hydroxybutyrates; D007773:Lactates; D008293:Malates; D013386:Succinates; D012978:Sodium Oxybate