Lecithin-cholesterol acyltransferase (LCAT) (LCAT)

Lecithin-cholesterol acyltransferase (LCAT) is a crucial enzyme in human lipid metabolism, primarily synthesized in the liver and secreted into the plasma where it associates with high-density lipoproteins (HDL). Its primary biological function is to catalyze the transfer of a fatty acyl group from phosphatidylcholine to free cholesterol, resulting in the formation of cholesteryl esters and lysolecithin (UniProt P04180). This esterification process is a key step in the maturation of HDL particles, transforming small, discoidal pre-beta HDL into larger, spherical alpha-HDL. By sequestering cholesterol into the hydrophobic core of HDL, LCAT maintains a concentration gradient that facilitates the efflux of excess cholesterol from peripheral tissues, such as macrophages in the arterial wall, back to the liver for excretion—a process known as reverse cholesterol transport (PubMed: 25150173). Genetic mutations in the LCAT gene lead to disorders such as Familial LCAT Deficiency (FLD) and Fish-eye disease, which are characterized by extremely low HDL-C levels, corneal opacities, and in the case of FLD, progressive renal failure (NIH: GARD). Therapeutic strategies targeting LCAT include recombinant human LCAT (e.g., MEDI6012) and small-molecule activators (e.g., DS-8190) aimed at treating atherosclerosis and chronic kidney disease by restoring or enhancing cholesterol esterification capacity.

Other names

Phosphatidylcholine-sterol acyltransferasePhospholipid-cholesterol acyltransferaseLCAT

Enzyme replacement or activation to catalyze the esterification of free cholesterol into cholesteryl esters on HDL particles, thereby promoting reverse cholesterol transport and HDL maturation.