Acetyl-CoA+Carboxylase

=__**Acetyl-CoA Carboxylase**__= = =

Structure
ACC consists of a carboxyltransferase (CT) domain and a biotin carboxyl carrier protein (BCCP) domain. As shown in figure 1, the CT domain contains two N-terminal monomers (cyan and magenta) and a C-terminal dimer (yellow and green). Its catalytic site for carboxyl transferase activty is located between the cyan and green subunits. Circled in figure 1 is the location of the acetyl-CoA substrate. = =

**Function**
ACC serves as the critical first step in lipogenesis. It catalyzes the irreversible carboxylation of acetyl-CoA to malonyl-CoA using biotin in two steps as shown in figure 2. The initial step involves usage of a carbonyl phosphate for the carboxylation of a biotin moiety that is covalently bonded ACC's BCCP domain. The second step involves usage of the carboxylated biotin to carboxylate acetyl-CoA in the CT domain active site to form malonyl-CoA.



**Regulation**
ACC is regulated by long term and short term mechanisms. In the long term, ACC expression can be downregulated at the genetic level by mRNA fragments. However, ACC has a relatively long half-life (60h). Thus the pre-existing ACC must regulated using short-term mechanisms. It can be allosterically regulated by cellular metabolites such as upregulation by citrate and downregulation by palmitoyl-CoA. It can also be covalently modified via phosphorylation by kinases such as PKA. For ACC, phosphorylation leads to deactivation while dephosphorylation leads to activation. = =

**Relevance to Lipolysis**
Malonyl-CoA serves to inhibit CPT1 which plays a role in fat oxidation. Lowering the activty of ACC by regulation would thus lead to less malonyl-CoA and less inhibition of carnitine acyltransferases.

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