LCAT Human, HEK

Lecithin-Cholesterol Acyltransferase (LCAT) is a crucial enzyme in lipid metabolism, playing a significant role in the conversion of free cholesterol into cholesteryl ester. This process is essential for the maturation of high-density lipoprotein (HDL) particles and the overall regulation of cholesterol levels in the body. The recombinant form of human LCAT, produced in Human Embryonic Kidney (HEK) cells, offers a valuable tool for research and therapeutic applications.

Human recombinant LCAT produced in HEK cells is a single, glycosylated polypeptide chain consisting of 429 amino acids. This includes a 13 amino acid Flag Tag fusion for purification purposes . The glycosylation of LCAT is essential for its stability and activity, mimicking the natural post-translational modifications that occur in human cells.

LCAT catalyzes the esterification of free cholesterol present on the surface of lipoproteins, particularly HDL. This reaction involves the transfer of a fatty acid from the sn-2 position of phosphatidylcholine (lecithin) to the hydroxyl group of cholesterol, forming cholesteryl ester and lysophosphatidylcholine. The cholesteryl ester then migrates to the core of the HDL particle, contributing to its maturation and enabling the reverse cholesterol transport (RCT) pathway .

LCAT is primarily synthesized in the liver and secreted into the bloodstream, where it associates with HDL particles. It is also found in other tissues, including the intestines and kidneys, albeit at lower levels. The enzyme’s activity is crucial for maintaining plasma cholesterol homeostasis and preventing the accumulation of free cholesterol in tissues.

The primary function of LCAT is to facilitate the maturation of HDL particles, which are responsible for transporting cholesterol from peripheral tissues to the liver for excretion. This process, known as reverse cholesterol transport, is vital for reducing the risk of atherosclerosis and cardiovascular diseases. By converting free cholesterol into cholesteryl ester, LCAT helps maintain the balance between cholesterol influx and efflux in cells .

LCAT activity is regulated by several factors, including apolipoproteins, lipids, and hormones. Apolipoprotein A-I (ApoA-I), the main protein component of HDL, is a critical activator of LCAT. Other apolipoproteins, such as ApoA-II and ApoC-I, can modulate LCAT activity to varying degrees. Additionally, the enzyme’s activity is influenced by the lipid composition of lipoproteins and the presence of certain hormones, such as insulin and glucagon .

Recombinant human LCAT has potential therapeutic applications in treating disorders related to cholesterol metabolism. For instance, LCAT deficiency, a rare genetic disorder, leads to the accumulation of free cholesterol in tissues and the formation of abnormal lipoproteins. Administration of recombinant LCAT can help restore normal cholesterol metabolism and alleviate symptoms associated with this condition .