Inhibition of ATP Citrate Lyase
(ACL) by bempedoic acid reduces cholesterol biosynthesis and lowers LDL-C by up-regulating the LDL receptor.
The product is an oral and once-daily ATP Citrate Lyase
(ACL) inhibitor, which reduces cholesterol and fatty acid synthesis in the liver.
This once-daily pill works in the liver to prevent cholesterol formation by inhibiting a key enzyme called ATP citrate lyase
Citric acid is eventually converted into fatty acid by the action of an enzyme called ATP citrate lyase
, resulting in the accumulation of fat.
Abbreviations: ACL, ATP citrate lyase; AMPK, AMP-activated protein kinase; Acetyl CoA, acetyl coenzyme A; ERK, extracellular signal-regulated kinase; HATs, histone acetyltransferases; HDACs, histone deacetylases; Hif1-[alpha], hypoxia inducible factor 1 alpha; MAT, methionine adenosyltransferase; MAVS; mitochondrial antiviral signaling protein; Met, methionine; mTOR, mechanistic target of rapamycin; NF[kappa]B, nuclear factor kappa B; PARP, poly(ADP-ribose) polymerase 1; SAM, S-adenosylmethionine; TCA, tricarboxylic acid cycle.
Abbreviations: Acetyl CoA, acetyl coenzyme A; ACL, ATP citrate lyase; HAT, histone acetyltransferase; HDAC, histone deacetylase; PARP, poly(ADP-ribose) polymerase 1.
Diminishing activity of NAD: ICDH through repression or significant decrease in intracellular AMP concentration via the activation of AMP deaminase would result in the accumulation of citrate which serves as the precursor for ATP citrate lyase
Measurements of those cells taken at 15 weeks of age showed that social isolation stimulated significant increases in the expression of three genes-Hk2 (hexokinase), Acly (ATP citrate lyase
) and Acaca (acetyl-CoA carboxykase).
Reactivity and inhibitor potential of hydroxycitrate isomers with citrate synthase, citrate lyase, and ATP citrate lyase
Both tissues had very low abundance for ATP citrate lyase
. The low transcript abundance of this enzyme in mammary tissue is consistent with its low activity level and minor contribution of glucose to fatty acid synthesis via acetyl-CoA in ruminant mammary gland (Hood et al., 1972).
With a targeted mechanism of action, bempedoic acid is a first-in-class, ATP Citrate Lyase
(ACL) inhibitor that reduces cholesterol biosynthesis and lowers LDL-C by up-regulating the LDL receptor.