ACCs are attractive targets for drug discovery against type 2 diabetes, obesity, cancer, microbial infections, other diseases and the plastid ACC of grasses is the target of action of three classes of commercial herbicides. Animals including humans, express two isoforms of acetyl-CoA carboxylase, ACC1and ACC2. The two enzymes are encoded by separate genes and display distinct tissue distribution and regulation. The ACC1 carboxylase are highly expressed in lipogenic tissues such as liver and adipose and their levels are regulated transcriptionally while their activities are regulated posttranslationally by phosphorylation/dephosphorylation of selected serine residues and by allosteric regulation through the action of citrate and palmitoyl-CoA. Acetyl-CoA Carboxylase catalyzes the initial step of fatty acid synthesis. This reaction is composed of two distinct half reactions; the ATP-dependent carboxylation of biotin with bicarbonate to form carboxybiotin followed by transfer of the carboxyl group from carboxybiotin to acetyl-CoA to form malonyl-CoA.
Dietary and hormonal states of the animal affect the level and activities of the ACC1 enzymes. A carbohydrate-rich, low-fat diet stimulates the expression and activities of ACC1 whereas starvation and diabetes reduce the ACC1 activities by repressing the expression of the ACC1 gene or by increasing the phosphorylation levels of the ACC1 protein. Also, treating diabetic animals with insulin increases the activity of the enzyme either by dephosphorylation of the protein or by activation of it with citrate and prolonged insulin treatment stimulates the synthesis of ACC1 protein.
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