Evidence that stimulation of gluconeogenesis by fatty acid is mediated through thermodynamic mechanisms.
We have studied the stimulatory effects of palmitate on the rate of glucose synthesis from lactate in isolated hepatocytes. Control of the metabolic flow was achieved by modulating the activity of enolase using graded concentrations of fluoride. Unexpectedly, palmitate stimulated gluconeogenesis even when enolase was rate-limiting. This stimulation was also observed when the activities of phosphoenolpyruvate carboxykinase and aspartate aminotransferase were modulated using graded concentrations of quinolinate and aminooxyacetate, respectively. Linear force-flow relationships were found between the rate of gluconeogenesis and indicators of cellular energy status (i.e. mitochondrial membrane and redox potentials and cellular phosphorylation potential). These findings suggest that the fatty acid stimulation of glucose synthesis is in part mediated through thermodynamic mechanisms.
Berry
M N
MN
Department of Medical Biochemistry, School of Medicine, Flinders University of South Australia, Bedford Park, Australia.
Gregory
R B
RB
Grivell
A R
AR
Henly
D C
DC
Phillips
J W
JW
Wallace
P G
PG
Welch
G R
GR
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D005459:Fluorides / Q000494:pharmacology; D005943:Gluconeogenesis / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D007773:Lactates / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013816:Thermodynamics
D007773:Lactates; D010169:Palmitic Acids; D011805:Quinolinic Acids; D000625:Aminooxyacetic Acid; D019308:Palmitic Acid; D010751:Phosphopyruvate Hydratase; D017378:Quinolinic Acid; D005459:Fluorides