Metabolism of HDL

HDL prevents oxidation of LDL complex.

HDL function as a naturally acting antioxidant which protect vessel wall from oxidative damage and resulting atherogenesis.

A i.e. HDL

• HDL contains good cholesterolQ. So there is an inverse relation between HDL (HDL₂) concentrations and coronoary heart disease. This is consistent with the function of HDL in reverse cholesterol transport.
• Diseases (eg. diabetes mellitus, lipid nephrosis, hypothyroidism and other considtions of hyperlipedimea) in which prolonged elevations of VLDL, IDL, LCD or chulomicron remnants in blood are often accompanied by premature or severe atherosclerosis. This makes LDL : HDL cholesterol ratio a good predective parameter for atherosclerosis & coronary heart disease.

Ans. is ‘a’ i.e., HDL

Reverse cholesterol transport

• All nucleated cells in different tissues synthesize cholesterol, but the excretion of cholesterol is mainly by liver in the bile or by enterocytes in gut lumen.
• So, cholesterol must be transported from peripheral tissue to liver for excretion.

o This is facilitated by HDL and is called reverse cholesterol transport because it transports the cholesterol in reverse direction to that is transported from liver to peripheral tissues through VLDL                        LDL cycle. Process

o HDL is synthesized in liver and small intestine.

o Nascent HDL contain phospholipids and unesterified cholesterol and Apo-A, C, E.

• This nascent HDL is secreted into circulation where it acquires additional unesterified cholesterol from peripheral tissues.

o Within the HDL particle, the cholesterol is esterified by lecithin – cholesterol acetyltransferase (LCAT) to form cholesteryl ester and additional lipid are transported to HDL from VLDL and chylomicrons.

o There are two pathway by which this cholesterol is transported to liver.

HDL can remove cholesterol from atheroma within arteries and transport it back to the liver for excretion or re-utilization, which is the main reason why HDL-bound cholesterol is sometimes called “good cholesterol”, or HDL-C. A high level of HDL-C seems to protect against cardiovascular diseases, and low HDL cholesterol levels (less than 40 mg/ dL or about 1mmol/L) increase the risk for heart disease.

The cholesterol contained in HDL particles is considered beneficial for cardiovascular health, in contrast to “bad” LDL cholesterol.

The HDL particles are referred to as scavengers because their primary role is to remove free (unesterified) cholesterol from the extrahepatic tissues.

HDL particles transport cholesterol from extrahepatic tissues to the liver (i.e. reverse cholesterol transport) which is then excreted through bile.

Reverse cholesterol transport

All nucleated cells in different tissues synthesize cholesterol, but the excretion of cholesterol is mainly by the liver in the bile or by enterocytes in the gut lumen. So, cholesterol must be transported from peripheral tissue to the liver for excretion. This is facilitated by HDL and is called reverse cholesterol transport because it transports the cholesterol in reverse direction to that is transported from the liver to peripheral tissues through the VLDL → LDL cycle.

Process

HDL is synthesized in the liver and small intestine. Nascent HDL contains phospholipids and unesterified cholesterol and Apo-A, C, E. This nascent HDL is secreted into circulation where it acquires additional unesterified cholesterol from peripheral tissues. Within the HDL particle, the cholesterol is esterified by lecithin – cholesterol acetyltransferase (LCAT) to form cholesteryl ester and additional lipid is transported to HDL from VLDL and chylomicrons. Apo-A₁ activates LCAT.

The total body cholesterol content varies from 130-150 grams.

LDL (low-density lipoprotein) transports cholesterol from the liver to the peripheral tissues and HDL (high-density lipoprotein) transports cholesterol from tissues to the liver.

Cells of extrahepatic tissues take up cholesterol from LDL.

Cholesteryl ester is tranfered from HDL to VLDL and chylomicrons in exchange with triglyceride by the cholesteryl ester transfer protein (CETP).

Ans. is ‘a’ i.e., HDL