Liver acetyl CoA carboxylase: insight into the mechanism of activation by tricarboxylic acids and acetyl CoA.

Recent investigations in this laboratory have shownl 2 that the isocitrate(or citrate-) activated form of liver acetyl CoA carboxylase (E.C. 6.4.1.2) is a large protein structure having a molecular weight of about four million. Electron microscopic examination of the carboxylase in the presence of isocitrate reveals' that it has a filamentous structure with dimensions of SG-100 A by up to 5000 A. Reversible dissociation to inactive protomeric subunits (molecular weight 409,000) occurs2 at low enzyme concentration in the carboxylation assay reaction mixture in the absence of isocitrate or at higher enzyme concentration in the presence of 0.5 M NaCl at pH 8.0. Reconstitution to the active filamentous form can be accomplished either by addition of isocitrate (or citrate) or by removal of NaCl and introduction of isocitrate by dialysis. The carboxylation of acetyl CoA catalyzed by liver acetyl CoA carboxylase involves the following two partial reactions (reactions 1 and 2):