TG, triacylglycerol; PL, phospholipid. Notes:
1 There are other fractions and sub-fractions not distinguished here. For instance, between VLDL and LDL there is an intermediate density lipoprotein (IDL) fraction; its half-life is short and its concentration normally low.
2 The proportions shown are approximate only and vary within each major class.
3 Apo lipoprotein C refers to the presence of apolipoproteins CI, CM and CM I (see Box 9.1); these are usually found together.
Box 9.1 The major apolipoproteins involved in lipoprotein metabolism
The complete amino acid sequences of the nine major human apolipoproteins are now known (AI, AII, AIV, B (48 and 100), CI, CII, CIII, D and E). The apolipoproteins other than apoB are often referred to as soluble apolipoproteins. They may exist in lipid-free form in the plasma and they may exchange between lipoprotein particles. Apolipoproteins of the groups A, C and E have similar gene structures and some homologous stretches of sequence, and are believed to have evolved from a common ancestral gene, whereas the genes for apoB and apoD have distinct structures.
Apolipoproteins AI, AII
These apolipoproteins are not closely related except in that they often occur together in lipoprotein fractions. AI is the better characterised. It has a relative molecular mass (M) of 28 000 (243 amino acids) and it has two major functions in lipoprotein metabolism. It is an activator of the enzyme lecithin-cholesterol acyl transferase (LCAT - see below). In addition, its amino acid sequence contains six repeated 22-amino acid sequences, which fold into alpha-helices with strong polar and non-polar faces. Thus, it has amphipathic properties that enable it to bind very strongly to various lipid classes including phospholipids and cholesterol. This property may give it a special role in interacting with cell membranes and 'collecting' cholesterol from the cells. It is produced in the cells of the small intestine and the liver.
This is a large protein found in chylomicrons, VLDL and LDL. There are two isoforms, called apolipoprotein B100 and apolipoprotein B48. The former contains 4536 amino acids (Mr 513 000). Apolipoprotein B48 is the N-ter-minal 2152 amino acids of this (Mr 241 000); in other words it represents about 48% of the apolipoprotein B100 molecule (and hence their names). It is produced from the same gene, by editing of the messenger RNA (in the cytoplasm) to introduce a stop codon. Apolipoprotein B48 is produced in intestinal cells and incorporated into chylomicrons, whereas B100 is produced in the liver and incorporated into VLDL. Since LDL are mostly produced from VLDL (see the text), LDL particles also contain B100. There is just one molecule of apolipoprotein B (B100 or B48) per particle: it wraps around the particle, its hydrophobic regions 'dipping down' into the core to anchor it. It functions as a receptor ligand.
Apolipoproteins CI, CII and CIII
Like the apolipoproteins A, these are not closely structurally related, but are often found together. Apolipoprotein CII is the best understood. It is a protein of Mr 8900 with 78 amino acids. It is an essential activator of the enzyme lipoprotein lipase (discussed earlier, in Sections 184.108.40.206 and 220.127.116.11); without it, lipoprotein lipase is not active. Thus, lipoprotein lipase can only act on the triacylglycerol in particles that contain apolipoprotein CII. It is produced in the liver. Apolipoprotein CI 11 may inhibit lipoprotein lipase, so that the ratio of CII to CIII in a particle seems to determine its susceptibility to lipolysis by lipoprotein lipase.
Apolipoprotein E is a protein of Mr 34 000 (299 amino acids), which exists in three major isoforms (known as E2, E3 and E4). Each person carries two alleles: thus, an individual may be E2/E3, E3/E3, etc. Apolipoprotein E functions as a receptor ligand. The different isoforms have different affinities for the receptor, and contribute to the variation in lipoprotein concentrations found within any population. Apolipoprotein E is found in association with the triacylglycerol-rich particles, chylomicrons and VLDL, and also in HDL. It is synthesised in many tissues, but the major source of apolipoprotein E in the plasma is probably the liver.
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