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ATP citrate lyase (ATP citrate synthase, ACLY) is a transferase that catalyzes the conversion of citrate and coenzyme A to acetyl-CoA. ACLY is the key regulator between the high rates of aerobic glycolysis and de novo lipid synthesis exhibited in many types of tumor cells.
ATP citrate lyase (ATP citrate synthase, ACLY), EC 22.214.171.124, is a transferase that catalyzes the conversion of citrate and coenzyme A (CoA) to acetyl-CoA and oxaloacetate. ACLY has been shown to be the key regulator between the high rates of aerobic glycolysis and de novo lipid synthesis, exhibited in many types of proliferating tumor cells.
ACLY is a homotetramer that is activated by hormones and growth factors involved in glucose uptake and metabolism, as well as anabolic growth. Insulin has been shown to enhance ACLY gene expression and protein phosphorylation, a process mediated by the PI 3-K-Akt signaling pathway. Activated ACLY converts cytoplasmic citrate into acetyl-CoA, which is an essential building block for fatty acid synthesis and the mevalonate pathway (cholesterol synthesis).
In normal cells de novo lipid synthesis is usually suppressed, however tumor cells generally exhibit enhanced rates of fatty acid synthesis. This is proposed to contribute to membrane biogenesis in proliferating cells. ACLY expression is upregulated in many types of tumors, whilst inhibition of ACLY has been shown to attenuate proliferation of certain types of cancer cells in vitro and in vivo.