Apolipoprotein C2

Apolipoprotein C-II (ApoC-II) is a protein that in humans is encoded by the APOC2 gene. ApoC-II is a component of very low-density lipoprotein (VLDL) and chylomicrons, playing a critical role in lipid metabolism by acting as a coenzyme for lipoprotein lipase (LPL), the enzyme necessary for the hydrolysis of triglycerides. This process is essential for the normal breakdown and removal of triglycerides from the bloodstream.

Function

ApoC-II is primarily synthesized in the liver and to a lesser extent in the intestine. It is secreted into the bloodstream, where it binds to circulating lipoproteins such as VLDL and chylomicrons. The primary function of ApoC-II is to activate lipoprotein lipase (LPL), an enzyme that is anchored to the endothelial cells lining the capillaries of muscle and adipose tissue. Upon activation by ApoC-II, LPL catalyzes the hydrolysis of triglycerides into free fatty acids and glycerol. These products are then taken up by the surrounding tissues for energy production or storage. Without the action of ApoC-II, the triglycerides in VLDL and chylomicrons cannot be hydrolyzed, leading to elevated levels of triglycerides in the blood, a condition known as hypertriglyceridemia.

Genetic and Clinical Aspects

Mutations in the APOC2 gene can lead to ApoC-II deficiency, a rare genetic disorder characterized by severe hypertriglyceridemia, recurrent episodes of pancreatitis, and an increased risk of cardiovascular disease. Diagnosis is typically made through genetic testing and measurement of ApoC-II levels in the blood. Treatment often involves dietary modifications to reduce fat intake, the administration of medium-chain triglycerides (which do not require LPL for their metabolism), and in some cases, infusion of fresh frozen plasma to provide functional ApoC-II.

Epidemiology

ApoC-II deficiency is a rare condition, with few cases reported in the medical literature. However, the prevalence of hypertriglyceridemia, which can be caused by a variety of genetic and lifestyle factors, is much higher. Elevated triglyceride levels are a known risk factor for cardiovascular disease, making the understanding and management of ApoC-II function significant in the context of public health.

Research Directions

Current research on ApoC-II focuses on understanding its structure-function relationships, the regulation of its expression, and its role in lipid metabolism and disease. There is also interest in developing therapeutic approaches for managing hypertriglyceridemia and ApoC-II deficiency, including gene therapy and novel pharmacological agents that can mimic or enhance the function of ApoC-II.