Apolipoprotein C

Abbtvviations apoC-lll, apolipoprotein C-lll apoA-l, apolipoprotein A-l apoA-ll, apolipoprotein A-ll CRP, C-reactive protein VLDL, very low density lipoprotein TG, triglycerides LDL-C, low density lipoprotein cholesterol HDL-C, high density lipoprotein cholesterol. 

There are striking similarities in the mechanisms of formation of chylomicrons by intestinal cells and of VLDL by hepatic parenchymal cells (Figure 25—2), perhaps because—apart from the mammary gland—the intestine and liver are the only tissues from which particulate lipid is secreted. Newly secreted or nascent chylomicrons and VLDL contain only a small amount of apolipoproteins C and E, and the frill complement is acquired from HDL in the circulation (Figures 25—3 and 25-4). Apo B is essential for chylomicron and VLDL formation. In abetalipoproteinemia (a rare disease), lipoproteins containing apo B are not formed and lipid droplets accumulate in the intestine and liver. 

Figure 25-3. Metabolic fate of chylomicrons. (A, apolipoprotein A B-48, apolipoprotein B-48 , apolipoprotein C E, apolipoprotein E HDL, high-density lipoprotein TG, triacylgiycerol C, cholesterol and cholesteryl ester P, phospholipid HL, hepatic lipase LRP, LDL receptor-reiated protein.) Only the predominant lipids are shown.

Fig. 9-4). Very low-density lipoprotein particles are released into the circulation where they acquire apolipoprotein E and apolipoprotein C-II from HDL. Very-low density lipoprotein loses its triglyceride content through the interaction with LPL to form VLDL remnant and IDL. Intermediate-density lipoprotein can be cleared from the circulation by hepatic LDL receptors or further converted to LDL (by further depletion of triglycerides) through the action of hepatic lipases (HL). Approximately 50% of IDL is converted to LDL. Low-density lipoprotein particles are cleared from the circulation primarily by hepatic LDL receptors by interaction with apolipoprotein B-100. They can also be taken up by extra-hepatic tissues or enter the arterial wall, contributing to atherogenesis.4,6... 

FIGURE 9. Endogenous lipoprotein metabolism. In liver cells, cholesterol and triglycerides are packaged into VLDL particles and exported into blood where VLDL is converted to IDL. Intermediate-density lipoprotein can be either cleared by hepatic LDL receptors or further metabolized to LDL. LDL can be cleared by hepatic LDL receptors or can enter the arterial wall, contributing to atherosclerosis. Acetyl CoA, acetyl coenzyme A Apo, apolipoprotein C, cholesterol CE, cholesterol ester FA, fatty acid HL, hepatic lipase HMG CoA, 3-hydroxy-3-methyglutaryl coenzyme A IDL, intermediate-density lipoprotein LCAT, lecithin-cholesterol acyltransferase LDL, low-density lipoprotein LPL, lipoprotein lipase VLDL, very low-density lipoprotein. 

R, Fruchart J-C, Dallongeville J. Fibrates downregulate apolipoprotein C-III expression independent of induction of peroxisomal acyl coenzyme A oxidase. J Clin Invest 1995 95 705-712. 

Diagnosis of lipoprotein lipase deficiency is based on low or absent enzyme activity with normal human plasma or apolipoprotein C-II, a cofactor of the enzyme. 

Hertz, R., Bishara-Schieban, J., and Bar-Tana, J. (1995). Mode of action of peroxisome pro-liferators as hypolipidemic drugs. Suppression of apolipoprotein C-III. /. Biol. Chem. 270, 13470-13475. 

G2. Ganesan, D., Bradford, R. H., Alaupovic, P., and McConathy, W. J., Differential activation of lipoprotein lipase form human post-heparin plasma, milk and adipose tissue by polypeptides of human serum apolipoprotein C. FEBS (Fed. Eur. Biochem. Soc.), Lett. 15, 205-208 (1971). 

Fig. 4.5.10 Analysis of core-1 mucin type -linked glycans derived from apolipoprotein C-III (ApoC-III). Serum-derived ApoC-III from a control (lane 1, left) and a CDG-IIx patient (lane 2, right) was investigated by IEF followed by antibody staining with a polyclonal rabbit-a-human ApoC-III antibody. ApoC-IIfi ApoC-IIEand ApoC-III0 indicate the variability in the amount of sialic acid residues linked to ApoC-III...

Table 4.5.7 Running conditions for isoelectric focusing of apolipoprotein C-III...

Noll B, Hackler R, Pelzer M, Pelzer S, Nusser P, Maisch B, Schaefer JR, Steinmetz A (1999) Semi-automated rapid isoelectric focusing of apolipoproteins C from human plasma using PhastSystem and immunofixation. Clin Chem Lab Med 37 643-648... 

Connelly PW, Vezina C, Maguire GF (1996) Quantification of apolipoprotein C-II by immunochemical and chromatographic methods. Methods Enzymol 263 188-208... 

Fojo SS, Brewer HB (1992) Hypertriglyceridaemia due to genetic defects in lipoprotein lipase and apolipoprotein C-II. J Intern Med 231 669-677... 

Haase R, Menke-Mollers I, Oette (1988) Analysis of human apolipoproteins C by isoelectric focusing in immobilized pH gradients. Electrophoresis 9 569-575... 

Lam CW, Yuen YP, Cheng WF, Chan YW, Tong SF (2006) Missense mutation Leu72Pro located on the carboxyl terminal amphipathic helix of apolipoprotein C-II causes familial chy-lomicronemia syndrome. Clin Chim Acta 364 256-259... 

Reina M, Brunzell JD, Deeb SS (1992) Molecular basis of familial chylomicronemia muta-tions in the lipoprotein lipase and apolipoprotein C-II genes. J Lipid Res 33 1823-1832... 

The protein moieties of lipoproteins are recognized by receptors on cell surfaces. In lipid uptake from the intestine, chylomicrons, which contain apolipoprotein C-II (apoC-ID, move from the intestinal mucosa into the lymphatic system, and then enter the blood, which carries them to muscle and adipose tissue (Fig. 17-1, step... 

Both chylomicrons and VLDL particles undergo similar processes in the capillary blood vessels, where their triacylglycerols are hydrolyzed to glycerol and free fatty acids by lipoprotein lipase 40 42a This enzyme requires for its activity the apolipoprotein C-II which is present in the chylomicrons and VLDL particles. Lipoprotein lipase is also known as the "clearing... 

Genes encoding for apolipoprotein C-I (APOC-I), apolipoprotein A1 (APOA-I), apolipoprotein C3 (APOCIII), and apolipoprotein A4 (APOA-IV) have all been subject to studies on longevity. In a small British study conducted in subjects aged 84 years and older, the authors examined APOE and APOC-I genes, as they are less than 10 kb apart, and APOC-I genotype... 

Anisimov SV, Volkova MV, Lenskaya LV, Khavinson VK, Solovieva DV, Schwartz EI. Age-associated accumulation of the apolipoprotein C-III gene T-455C polymorphism C allele in a Russian population. J Gerontol A Biol Sci Med Sci 2001 56 B27-B32. 

Apolipoprotein C-I can be isolated from VLDL (B56, S52) or HDL (08) by repeated chromatography. It has been sequenced and found to contain 57 residues (J8, S33). It appears to be highly helical on lipid binding (J7), with three lipid-binding helical sequences predicted by Chou-Fasman analysis (S22). Both native and synthetic apoC-I bind lipid, and also activate LCAT (H7, S34, S46). This dual activity is probably due to the peptide which contains amino acids 17-57 this sequence appears to activate LCAT, and the sequence 32-57 appears to bind lipid (S49). ApoC-I readily selfassociates in aqueous solution (07). 

Apolipoprotein C-II can also be isolated from VLDL or HDL (H20, L5, N3). It contains 78 residues (J3) and has been shown by Chou-Fasman analysis to bind phospholipids (M26, M40), with three predicted helical sequences (M26). ApoC-II has attracted a great deal of attention because it activates one of the most important enzymes in plasma lipid metabolism, lipoprotein lipase, responsible for the hydrolysis of triglyceride in chylomicrons and VLDL. Sparrow and Gotto have summarized a number of studies on structure-function relationships (S52). These, taken together, indicate that there are separate functional domains in apoC-II, in that lipoprotein lipase activation is mediated by residues 55-78 and phospholipid binding by... 

H28. Holdsworth, G., Stocks, J., Dodson, P., and Calton, D. J., An abnormal triglyceride-rich lipoprotein containing excess sialylated apolipoprotein C-III. ]. Clin. Invest. 69, 932-939 (1982). 

H29. Holmquist, L., Quantitation of human serum very low density apolipoproteins C-I, C-II, C-III and E by enzyme immunoassay. J. Immunol. Methods 34, 243-251 (1980). 

K9. Kashyap, M. L., Srivastava, L. S., Hynd, B. A., Gartside, P. S., and Perisutti, G., Quantitation of human apolipoprotein G-III and its subspecies by radioimmunoassay and analytical isoelectric focusing Abnormal plasma triglyceride-rich lipoprotein apolipoprotein C-III subspecie concentrations in hypertriglyceridemia. J. Lipid Res. 22, 800—810 (1981). 

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