Pathway of gluconeogenesis from D- and L-glycerate in rat hepatocytes.
Synthesis of glucose from 10 mM D-glycerate by hepatocytes isolated from rats fasted 24 h was inhibited by 3-aminopicolinate (3AP), 3-mercaptopicolinate (3MP), and aminoxyacetate (AOA). The inhibition by AOA can be exerted over that caused by either of the picolinates. The effects of 3AP and 3MP were not additive, and cannot be ascribed totally to inhibition of reducing equivalent transfer by their inhibitory effect on phosphoenolpyruvate carboxykinase. The time course and dependence on substrate concentration of gluconeogenesis from L-glycerate was similar to those from D-glycerate, even though the cellular content of D-glycerate was markedly less when L-glycerate was the substrate. Gluconeogenesis from L-glycerate was not significantly affected by 3AP or 3MP, but was inhibited by AOA. The degree of inhibition by AOA of glucose synthesis from L-glycerate was greater than that from D-glycerate. Studies employing [14C]paraformaldehyde revealed that hydroxypyruvate may be converted to dihydroxyacetone in the hepatocyte. A hitherto unknown inhibition site of 3AP and 3MP is inferred and a dual pathway of D- and L-glycerate gluconeogenesis consistent with these results is proposed.
Chen
K S
KS
Institute for Enzyme Research, University of Wisconsin, Madison 53705.
Lardy
H A
HA
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D002854:Chromatography, Paper; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000096:biosynthesis; D005988:Glyceric Acids / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000037:antagonists & inhibitors; D010848:Picolinic Acids / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D005988:Glyceric Acids; D010848:Picolinic Acids; C018451:3-aminopicolinic acid; D000625:Aminooxyacetic Acid; C008363:3-mercaptopicolinic acid; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005947:Glucose