What Is LCAT and Its Function in the Body?

Lecithin-cholesterol acyltransferase (LCAT) is an enzyme synthesized by the liver and found circulating in the bloodstream. It is essential for managing cholesterol, a substance found in all cells. The enzyme interacts with lipoprotein particles, which transport fats and cholesterol through the blood, and its activity specifically influences high-density lipoprotein (HDL) particles. This interaction helps regulate the form and destination of cholesterol within the body’s transport system.

The Biochemical Function of LCAT

LCAT performs a chemical reaction called esterification. It transfers a fatty acid from a phospholipid molecule called phosphatidylcholine (lecithin) to a free cholesterol molecule. This reaction converts free cholesterol into a cholesteryl ester. Cholesteryl esters are more water-repelling than free cholesterol, causing them to move from the surface of a lipoprotein particle to its core, repackaging cholesterol into a more stable form for transport.

This chemical modification is integral to the development of HDL particles. Newly formed, disc-shaped HDL particles are known as nascent HDL. As LCAT esterifies free cholesterol on their surface, the resulting cholesteryl esters accumulate within the particle’s core. This accumulation causes the HDL particle to transform into a larger, spherical, mature form, which significantly increases its cholesterol-carrying capacity.

The maturation process driven by LCAT allows HDL to function effectively. By converting free cholesterol into cholesteryl esters, LCAT creates a concentration gradient. This gradient encourages more free cholesterol to move from surrounding tissues onto the HDL particle’s surface. Without LCAT’s action, HDL particles would remain in their nascent, less effective state, unable to properly collect and store cholesterol.

LCAT and Reverse Cholesterol Transport

LCAT’s function is a component of a larger physiological process known as reverse cholesterol transport (RCT). This pathway is the body’s primary mechanism for removing excess cholesterol from peripheral tissues, such as artery walls, and returning it to the liver. Once in the liver, cholesterol can be processed for removal from the body through bile. RCT acts as a cleanup system, preventing the buildup of cholesterol where it could contribute to health problems.

LCAT facilitates this process by enabling HDL particles to become efficient cholesterol carriers. As mature HDL circulates and collects cholesterol from cells, the subsequent esterification by LCAT is what makes the transport effective. By converting free cholesterol and sequestering the resulting cholesteryl esters in the HDL core, LCAT effectively traps the cholesterol, preventing it from moving back into the tissues.

This trapping mechanism ensures that cholesterol transport is a one-way street from the body’s tissues toward the liver. The mature, spherical HDL particles, loaded with cholesteryl esters, are the vehicles for this journey. This system of cholesterol removal from areas like the arterial wall is part of maintaining cardiovascular health.

LCAT Deficiency Disorders

Mutations in the LCAT gene, located on chromosome 16, can lead to rare inherited conditions known as LCAT deficiency. These are autosomal recessive disorders, meaning an individual must inherit a mutated copy of the gene from both parents. These mutations result in an LCAT enzyme with either no function or significantly reduced function. The core issue is the body’s inability to properly esterify cholesterol.

There are two primary forms of LCAT deficiency. The more severe form is Familial LCAT Deficiency (FLD), characterized by a complete or near-complete absence of LCAT activity. In FLD, the body cannot effectively esterify cholesterol on any lipoprotein, leading to systemic consequences.

A milder variant is known as Fish-eye Disease (FED). In FED, the LCAT enzyme is partially active but is specifically unable to act on HDL particles. This partial activity means the symptoms are less severe and more restricted than those in FLD. The inability to mature HDL particles remains the central problem in both conditions.

Clinical Aspects of LCAT Deficiency

The clinical presentation of LCAT deficiency varies between its two forms. The most prominent sign in both FLD and FED is the development of significant corneal opacities, where the eye’s clear outer layer becomes cloudy due to lipid deposits. This clouding, which can lead to severe visual impairment, resembles a boiled fish’s eye, giving Fish-eye Disease its name. Patients with the more severe FLD also develop progressive kidney disease that can advance to renal failure and a form of anemia called hemolytic anemia.

Diagnosis of LCAT deficiency begins with laboratory blood tests that reveal a characteristic lipid profile. These tests show extremely low levels of HDL cholesterol and a high proportion of unesterified cholesterol. While these findings are strong indicators, a definitive diagnosis requires genetic testing to identify mutations in the LCAT gene. A kidney biopsy may be performed to assess the extent of lipid deposition and damage.

Currently, there is no cure for LCAT deficiency, so treatment is focused on managing symptoms and preventing complications. Patients are advised to follow a low-fat diet to reduce the lipid load in the body. For those with FLD, managing kidney disease is a priority, often involving medications like ACE inhibitors. In advanced cases, dialysis or a kidney transplant may be necessary, while severe vision loss can be addressed with a corneal transplant. Research into potential treatments like enzyme replacement therapy is ongoing.