Lipoprotein metabolism - Essay Example

High-Density Lipoprotein (HDL) Describe The Structure and Function of High Density Lipoprotein (HDLS) In Lipoprotein Metabolism in ManStructure of High-Density Lipoprotein (HDL)HDL belongs to a group of heterogeneous lipoprotein that contains about equal amounts of protein and lipid. The particles of HDL are characterized by small size (Stroke’s diameter of 5-17 nm) and high density (>1.063 g/mL). The various subclasses of HDL vary in qualitative and quantitative content of apolipoproteins, lipid transfer proteins, lipids, and enzymes, resulting in density, shape, antigenicity charge and size.

Most of predominant HDL protein (apolipoprotein A-1) migrates with α-electrophoretic mobility in agarose gels and is designated α–LpA-I. This part accounts for the largest part of the cholesterol that is quantified as HDL-C in clinical laboratory. α-HDL can be fractionated further by density into HDL3 and HDL2, by apolipoprotein composition and size. About 5-15% of apo A-1 in the human plasma is linked to pre–β-electrophoretic mobility particles. This is further differentiated into pre–β3-LpA-I, β1-LpA-I and pre–β2-LpA-I particles.

These particles where reverse cholesterol transport occurs. This occurs in extravascular compartments. It is not clear where the HDL particles and pre–β-electrophoretic mobility originates from. There are several mechanisms that have been proposed including cholesteryl ester transfer protein (CETP), direct interaction between cell membrane and free apolipoproteins, hepatic lipase (HL), release during the HDL interconversion by phospholipid transfer protein (PLTP) and direct secretion from enterocytes into plasma.

Functions of HDLHigh-density lipoprotein is produced in the intestine and liver. It plays a key role in the reverse cholesterol transport. By accepting free cholesterol from the peripheral tissues, HDL lowers the blood cholesterol levels. HDL exchanges lipids and proteins with other lipoproteins. It donates apoproteins E and C11 to nascent VLDL’s. HDL also produces a paraoxonase enzyme. This enzyme inhibits the oxidation of low-density lipoprotein. The HDL precursor particles can also absorb free cholesterol from the cell membrane in a process mediated by apoA-1, ApoA-IV and ATP binding cassette transporter 1.

ApoA-1 is the HDL’s major apolipoprotein. It activates the cholesterol acyltransferase (LCAT) (a lecithin enzyme) that esterifies the free accepted cholesterol to increase the efficiency of cholesterol packaging for transport. By acquisition of additional esters, triglycerides, and apolipoproteins, the particles of HDL3 are transformed into HDL2 particles which are relatively larger. By estension, HDL plays a role in transferring the apoproteins E and C11 and cholesterol from the peripheral tissues to the liver (Figure 1).

This reverse cholesterol transport process is important because it helps relieve the peripheral cells from the cholesterol burden. The reverse cholesterol transport may take three routes. First, the liver can take up via LDL receptor large HDL particles with many apoE copies. Secondly, the liver when mediated by scavenger receptor B1 can selectively take the accumulated cholesteryl esters. The scavenger receptor B1 is often expressed in nonplacental steroidogenic and liver tissues. Thirdly, the cholesteryl ester transfer protein can transfer cholesteryl esters from HDL to trygleceride-rich lipoproteins.

Figure 1: The transfer of proteins from HDL to chylomicronsFigure 2: role of HDL’s in lipoprotein metabolism