[12] In mammals, PC plays a crucial role in gluconeogenesis and lipogenesis, in the biosynthesis of neurotransmitters, and in glucose-induced insulin secretion by pancreatic islets.

[14] Structural studies of PC have been conducted by electron microscopy, by limited proteolysis, and by cloning and gasa sequencing of genes and cDNA encoding the enzyme.

Each subunit contains a single biotin moiety acting as a swinging arm to transport carbon dioxide to the catalytic site that is formed at the interface between adjacent monomers.

[17] The Staphylococcus aureus tetramer in complex with the activator coenzyme A is highly symmetric, possessing 222 symmetry, and has been confirmed by cryo-EM studies.

[16] In contrast the Rhizobium etli, tetramer in complex with ethyl-CoA, a non-hydrolyzable analog of acetyl-CoA, possesses only one line of symmetry.

The allosteric binding site in PC offers a target for modifiers of activity that may be useful in the treatment of obesity or type II diabetes, and the mechanistic insights gained from the complete structural description of RePC (R. etli) permit detailed investigations into the individual catalytic and regulatory sites of the enzyme.

[16] In the second reaction, occurring in the CT domain of an adjacent monomer, carbon dioxide is transferred to the acceptor molecule, pyruvate, to form oxaloacetate.

The reaction proceeds via the removal of a proton from pyruvate, by an as yet unidentified active site residue, to generate an enolate intermediate.

The OAA is then decarboxylated and simultaneously phosphorylated, which is catalyzed by one of two isoforms of phosphoenolpyruvate carboxykinase (PEPCK) either in the cytosol or in the mitochondria to produce PEP.

During fasting or starvation when endogenous glucose is required for certain tissues (brain, white blood cells and kidney medulla), expression of PC and other gluconeogenic enzymes is elevated.

[23] Aside from the role of PC in gluconeogenesis, PC serves an anaplerotic role (an enzyme catalyzed reaction that can replenish the supply of intermediates in the citric acid cycle) for the tricarboxylic acid cycle (essential to provide oxaloacetate), when intermediates are removed for different biosynthetic purposes.

[30][31] Concurrently adipose tissue develops insulin resistance causing accumulation of triacylglycerols and non-esterified fatty acids in circulation; these not only further impairing β-cell function,[31][32] but also further decreasing PC expression.