Epinephrine Inhibition of Pyruvate Carboxylation In Adipose Tissue

Epinephrine Inhibition of Pyruvate Carboxylation In Adipose Tissue

Rafiqur Rahman1,Robert L. Jungas2

1Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka-1000, Bangladesh,2Robert L. Jungas, Department of Cell Biology, University of Connecticut Health Center Farmington, Ct. 06032, USA

ABSTRACT: One µM epinephrine inhibited the incorporation of H14CO3– into protein by rat adipose tissue 50-60%, while it inhibited protein synthesis measured by the incorporation of tritiated water into protein by only 40%. The inhibition was blocked by either DL- propranol or by insulin. Epinephrine inhibited the incorporation of H14CO3– into acid-soluble products by 37%. A much greater inhibitory effect (76%) was observed on pyruvate carboxylation catalyzed by the infranatant fraction of homogenates prepared from adipocytes previously exposed to the hormone for 15 min. Freeze- thawing of the infranatant to rupture the mitochondrial membranes did not reduce the extent of inhibition, indicating that the hormonal effect was not on pyruvate transport. Addition of both ATP (5 mM) and acetyl CoA (0.25 mM) to the freeze-thawed mitochondrial suspensions increased pyruvate carboxylation forty-fold, and totally abolished the inhibitory effect of epinephrine treatment. It is suggested that the inhibitory action of epinephrine on bicarbonate fixation seen in intact cells and in mitochonrial suspensions results from the ability of the hormone to activate lipolysis, increase the level of uncoupling fatty acids in the cell, and therefore lower cellular ATP levels.

KEYWORDS: bicarbonate, insulin, adipocytes, tritiated water, CO2 fixation, protein synthesis, ATP

CORRESPONDENCE: Rafiqur Rahman