Regulation of the structure and activity of pyruvate carboxylase by acetyl CoA

Abstract

In this review we examine the effects of the allosteric activator, acetyl CoA on both the structure and catalytic activities of pyruvate carboxylase. We describe how the binding of acetyl CoA produces gross changes to the quaternary and tertiary structures of the enzyme that are visible in the electron microscope. These changes serve to stabilize the tetrameric structure of the enzyme. The main locus of activation of the enzyme by acetyl CoA is the biotin carboxylation domain of the enzyme where ATP-cleavage and carboxylation of the biotin prosthetic group occur. As well as enhancing reaction rates, acetyl CoA also enhances the binding of some substrates, especially HCO3−, and there is also a complex interaction with the binding of the cofactor Mg2+. The activation of pyruvate carboxylase by acetyl CoA is generally a cooperative processes, although there is a large degree of variability in the degree of cooperativity exhibited by the enzyme from different organisms. The X-ray crystallographic holoenzyme structures of pyruvate carboxylases from Rhizobium etli and Staphylococcus aureus have shown the allosteric acetyl CoA binding domain to be located at the interfaces of the biotin carboxylation and carboxyl transfer and the carboxyl transfer and biotin carboxyl carrier protein domains.

The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes

“…For example, although acute insulin signalling following a meal can decrease messenger RNA expression of gluconeogenic enzymes, it probably does not acutely alter the protein levels of these enzymes. Gluconeogenic enzymes are also conventionally thought to be subject to allosteric activation: acetyl coenzyme A (acetyl-CoA) activates pyruvate carboxylase 20,21 , and fructose-2,6-bisphosphate inhibits fructose-1,6-bisphosphatase 22 . And, although insulin might activate glycogen synthesis, glucose is necessary to inhibit glycogen phosphorylase and effectively promote net hepatic glycogen synthesis 23,24 .…”

Regulating Pyruvate Carboxylase in the Living Culture of Aspergillus Terreus Nrrl 1960 by l-Aspartate for Enhanced Itaconic Acid Production

“…This eventually led to the reduction in biomass synthesis [7,20]. [21]. From the above-mentioned claim and the metabolic response of A. terreus to L-aspartate during the growth phase, L-aspartate was introduced into the pregrown culture of A. terreus during the production phase.…”

Cerebral Gluconeogenesis and Diseases

“…The reaction is dependent on biotin, adenosine triphosphate (ATP) and magnesium (Jitrapakdee and Wallace, 1999; Jitrapakdee et al, 2008). Acetyl-coenzyme A (Acetyl-CoA) is the allosteric effector of PC in humans (Adina-Zada et al, 2012). …”