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Malonyl-coenzyme A
In fat synthesis, the enzyme pyruvate dehydrogenase, which forms acetyl-coA, and also acetyl CoA carboxylase which forms malonyl-coA are obvious control points. These are activated by insulin. This leads to an overall increase in the levels of malonyl-coenzyme A, which is the substrate required for fat synthesis. Thus, the flux down storage pathway is increased when there is sufficient glucose in the 'fed' state.
Acetyl-coA carboxylase
Insulin affects ACC in a similar way to PDH. It leads to its dephosphorylation. Glucagon has an antagonistic effect and increases phosphorylation, therefore inhibiting ACC, and slowing fat synthesis. This inhibition mechanism is thought to be something to do with ACC-dependent protein kinase. Affecting ACC affects the rate of acetyl-coA conversion to malonyl-coA. Malonyl-coA increae pushes the equilibrium over to increase production of fatty acids through biosynthesis. AMP activated protein kinase acts as a measure of the ATP needs of a cell and acts to phosphorylse ACC. When ATP is depleted there is a rise in 5'AMP. This rise activates AMP-activated protein kinase, which phosphorylates ACC and thereby inhibits fat synthesis. This is a useful way to ensure that glucose is not diverted down a storage pathway in times when energy levels are low. ACC is also activated by citrate. This means that when there is abundant acetyl-coA in the cell cytoplasm for fat synthesis it proceeds at an appropriate rate. Note: Research now shows that glucose metabolism (exact metabolite to be determined), aside from insulin's influence on lipogenic enzyme genes, can induce the gene products for Liver pyruvate kinase, acetyl-CoA carboxylase and fatty acid synthase. These genes are induced by the transcription factors ChREBP/Mlx via high blood glucose levels and presently unknown signaling events. Insulin induction is due to SREBP-1c, which is also involved in cholesterol metabolism. Work from Howard Towle, Catherine Postic, and K. Uyeda can be referenced for ChREBP/Mlx effects described above. Further Reading What is Lipogenesis?
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