ATP Citrate Lyase

Supporting information

ATP citrate lyase (ATP citrate synthase, ACLY), EC 2.3.3.8, 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.

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Gene Species Gene Symbol Gene Accession No. Protein Accession No.
ACLY Human ACLY NM_001096 P53396
Mouse Acly NM_001199296 Q91V92
Rat Acly NM_016987 NP_058683

Literature for ATP Citrate Lyase

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