LCAT

LCAT is synthesized primarily in the liver and circulates in plasma bound to HDL (activated by apoA-I). It catalyzes the transfer of a fatty acid from lecithin (phosphatidylcholine) to free cholesterol, forming cholesteryl ester and lysolecithin. This esterification traps cholesterol within the hydrophobic core of HDL particles, converting discoidal nascent HDL into mature spherical HDL3 and HDL2, which is essential for reverse cholesterol transport (movement of cholesterol from peripheral tissues back to the liver).

LCAT deficiency (Familial LCAT Deficiency, or 'Fish-eye disease' in partial deficiency) results in impaired esterification of cholesterol, causing free cholesterol accumulation in various tissues. Clinical features include: - Corneal opacities (due to cholesterol deposition, giving a 'fish-eye' appearance) - Hemolytic anemia (due to abnormal red cell membrane lipid composition, causing target cells and hemolysis) - Proteinuria and progressive renal failure (due to lipid deposition in glomeruli, sometimes called glomerulosclerosis) - Low HDL cholesterol levels on lipid panel

LCAT deficiency is inherited in an autosomal recessive pattern. Complete deficiency (classic Norum disease) causes more severe multisystem findings, while partial deficiency (fish-eye disease) primarily causes corneal opacities without significant renal or hematologic disease.

LCAT is clinically relevant in USMLE contexts primarily in the setting of dyslipidemia workups, differential diagnosis of low HDL, and understanding of reverse cholesterol transport pathways which are also targeted by drugs like CETP inhibitors and niacin.