Lipogenesis - Fatty Acid Synthesis - Control and Regulation - PDH Dephosphorylation

PDH Dephosphorylation

Pyruvate dehydrogenase is dephosphorylated in response to increased insulin signalling. The dephosphorylated form is more active.

As insulin binds to cellular surface transmembrane receptors that intracellularly activate the adenylate cyclase enzyme that catalyze cAMP (cyclic AMP) production from ATP. The increased intracellular cAMP, acts as a second messenger, in response to the insulin binding. cAMP activates protein kinase enzyme that in turn activates phosporylase enzyme that phosphorylates and in doing so activates a number of different intracellular enzymes such as the pyruvate dehydrogenase that dehydrates pyruvate to form AcCoa. So, an extracellular hormone, insulin, can in multistep activation (cascade) activate an enzyme in the cellular matrix.

This mechanism leads to the increased rate of catalysis of this enzyme, so increases the levels of acetyl-CoA. Increased levels of acetyl-CoA will increase the flux through not only the fat synthesis pathway but also the citric acid cycle.

Note: The above is incorrect; insulin does not activate adenylate cyclase. Epinephrine via the beta adrenergic receptor and glucagon via its receptor activate adenylate cyclase, increasing cAMP levels and PKA activity. Insulin activates cAMP phosphodiesterase, which breaks down cAMP. This leads to a decrease in cAMP levels and therefore a decrease in PKA activity. With regard to Pyruvate dehydrogenase, this enzyme is inhibited when phosphorylated. Insulin stimulates the activity of pyruvate dehydrogenase phosphatase. This enzyme removes the phosphate from pyruvate dehydrogenase, allowing for conversion of pyruvate to acetyl-CoA.