Regulation of acetyl-CoA carboxylase

Abstract

Acetyl-CoA carboxylase (ACC) catalyses the formation of malonyl-CoA, an essential substrate for fatty acid synthesis in lipogenic tissues and a key regulatory molecule in muscle, brain and other tissues. ACC contributes importantly to the overall control of energy metabolism and has provided an important model to explore mechanisms of enzyme control and hormone action. Mammalian ACCs are multifunctional dimeric proteins (530-560 kDa) with the potential to further polymerize and engage in multiprotein complexes. The enzymatic properties of ACC are complex, especially considering the two active sites, essential catalytic biotin, the three-substrate reaction and effects of allosteric ligands. The expression of the two major isoforms and splice variants of mammalian ACC is tissue-specific and responsive to hormones and nutritional status. Key regulatory elements and cognate transcription factors are still being defined. ACC specific activity is also rapidly modulated, being increased in response to insulin and decreased following exposure of cells to catabolic hormones or environmental stress. The acute control of ACC activity is the product of integrated changes in substrate supply, allosteric ligands, the phosphorylation of multiple serine residues and interactions with other proteins. This review traces the path and implications of studies initiated with Dick Denton in Bristol in the late 1970s, through to current proteomic and other approaches that have been consistently challenging and immensely rewarding.

Paeoniflorin Protects against Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet in Mice

“…19) And the inactivation of ACC decreased the activity of MC. 20) MC is a fatty acid precursor. It is also an inhibitor of camitine palmitoyltransferase 1 (CPT-1) which is the rate-limiting enzyme of mitochondrial fatty acid oxidation.…”

Copper deficiency results in AMP-activated protein kinase activation and acetylCoA carboxylase phosphorylation in rat cerebellum

“…When activated, one specific way AMPK helps maintain cellular energy stores is by shutting down biosynthetic processes like fatty acid synthesis by phosphorylating and inhibiting ACC, the rate limiting enzyme in this biosynthetic process (Brownsey et al, 2006;Munday, 2002). In the current experiments, at both ages in postnatal development, cerebellar levels of pACC were higher in Cu− rat pups, consistent with impairment in enzyme activity.…”

“…3). Western blot analysis used an antibody specific to phosphorylation of serine 79, the AMPK specific ACC target residue (Brownsey et al, 2006;Munday, 2002). Evaluation of both P13 and P24 cerebella (Experiment I) revealed higher content of phosphorylated ACC (pACC) in Cu− cerebella compared to age matched Cu+ controls, 94% and 61%, respectively.…”

The expression of genes involved in jejunal lipogenesis and lipoprotein synthesis is altered in morbidly obese subjects with insulin resistance

“…ACC1 gene has an inducible expression in response to insulin. 41 However, in a situation with only high levels of glucose or insulin, there is only a higher apo A-IV mRNA expression, suggesting a higher synthesis of triglyceride-rich lipoproteins, but without an increase of its triglyceride content, owing to the absence of an increase of DGAT2, MTTP, and ACC1. On the other hand, PDHB, SREBP-1c, and ACLY behave in an opposite manner in response to insulin.…”