A novel mechanism for Ca(2+)-dependent regulation of hepatic gluconeogenesis: stimulation of mitochondrial phosphoenolpyruvate synthesis by Ca2+.
1. Isolated guinea pig liver mitochondria were used to assess a possible effect of Ca2+ on the rate of phosphoenolpyruvate (PEP) synthesis. 2. PEP synthesis from 2-oxoglutarate (2-OG), but not from malate, was stimulated by [Ca2+] between 200 and 1200 nM. The effect was more pronounced at low [2-OG] (i.e. 0.1 and 0.3 mM) and it reached 58 and 22%, respectively, at 1200 nM as compared to 200 nM [Ca2+]. 3. Ruthenium red (1.8 microM) totally suppressed the stimulatory effect of Ca2+. 4. Malonate (5 mM) abolished PEP formation with 2-OG alone but inhibited only slightly the process with 2-OG + malate. 5. The results suggest that the stimulation by Ca2+ of 2-OG dehydrogenase and, therefore, of GTP synthesis, provides a mechanism for an enhanced PEP synthesis and for regulation of hepatic gluconeogenesis by Ca(2+)-mobilizing hormones.
Deaciuc
I V
IV
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
D'Souza
N B
NB
Miller
H I
HI
D000818:Animals; D002118:Calcium / Q000502:physiology*; D005943:Gluconeogenesis; D006168:Guinea Pigs; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D010728:Phosphoenolpyruvate / Q000378:metabolism*
D010728:Phosphoenolpyruvate; D002118:Calcium