Apolipoprotein C-II

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... 

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. 

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... 

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... 

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... 

Fig. 12. The separation of a mixture of C-apolipoproteins (VLDL) on a Waters fi-Bondapak alkylphenyl column with a mobile phase of 1% triethylammcmium phosphate, pH 3.2, and acetonitrile as the organic modifier using several gradient slopes. The flow rate was 1.5 ml/min. The different proteins were identified by amino acid analysis and pure standards as follows 1, olipoprotein C-I 2-4, apolipoprotein C-111 with 2,1, and 0 mol of sialic acid in the carbohydrate side chains, respectively 5, apolipoprotein C-II. Adapted from Hancock and Sparrow (1981c).

Peripheral tissues uch as muscle, adipose tissue, and the I acta ting breast contain both hoTmone-sensitive lipnse and lipoprotein lipase. This second lipase, mentioned in the lipoprotein section of Chapter ft, requires apolipoprotein C-II as a cofactor. The lipase is secreted by cells and migrates through the interstitial fluid to the capillary, where it becomes bound to the membrane with its active site exposed to the bloodstream. This binding to the luminal wall of the capillary occurs by attachment to a polymer called glycosaminoglycan. 

As chylomicrons enter the l)Tnphatic system and the bloodstream, they encounter other lipoprotein particles, such as HDLs. HDLs have a number of functions. One HDL protein, apolipoprotein C-II (Apo C-II), is transferred from an HDL to a chylomicron after it leaves the enterocyte. Apo C-EI is a cofactor of lipoprotein lipase, an enzyme that resides on the wall of the capillaries in tissues such as muscle and adipose. This enzyme is loosely boimd to the lumenal side of the capillary, exposed to the bloodstream. In conjunction with the apo C-II of a chylomicron, it catalyzes the hydrolysis of the TGs of the chylomicron. The free fatty acid products then pass through the wall of the capillary and enter the tissue. 

Apolipoprotein C-II serves as a cofactor for lipoprotein lipase. This situation resembles that of colipase, which is required for the activity of pancreatic lipase. When chylomicrons or VLDLs pass through the capillaries of an organ, they encounter lipoprotein lipase. About half the fatty acids liberated by the action of this enzyme are taken up by the tissue, whereas the rest remain in the circulation and return (bound to albumin) to the liver. Apo C-II is part of the structure of chylomicrons and VLDLs. 

Streicher, R., Geisel, J., Weisshaar, C., Avd, H., Oette, K., Muller-Wieland, D., and Krone, W. (1996). A single nucleotide substitution in the promoter region of the apolipoprotein C-II gene identified in individuals with chylomicronemia. J. Lipid Res. 37,2599-2607. 

Abbreviations GcL, Geotrichum candidum lipase hPL, human pancreatic lipase RmL, Rhizomucor miehei lipase hHL, human hepatic lipase hLPL, human lipoprotein lipase hLAL, human lysosomal acid lipase hGL, human gastric lipase BAL, bile salt-activated lipase HSL, hormone-sensitive lipase CLP, colipase AChE, Torpedo cal omica acetylcholinesterase cDNA, complementary deoxyribonucleic acid VLDL, very low-density lipoprotein IDL, intermediate-density lipoprotein HDL, high-density lipoprotein apoC-II, apolipoprotein C-II. 

Jackson RL, Tajima S, Yamamura T, Yokoyama S, Yamamoto A. Comparison of apolipoprotein C-II-deftcient triacylglycerol-rich lipoproteins and trioleoyiglycerol/phosphatidylcholine-stabilized particles as substrates for lipoprotein lipase. Biochim BiophysActa 1986 875 211-19. 

Chylomicrons, large triglyceride-rich particles containing apolipoprotein B-48, B-lOO, and E, are formed from dietary fat solubilized by bile salts in intestinal mucosal cells (Fig. 21-2). Chylomicrons normally are not present in the plasma after a fast of 12 to 14 hours and are catabolized by lipoprotein lipase (LPL), which is activated by apolipoprotein C-II, in the vascular endothelium and hepatic lipase to form chylomicron remnants. The remnants that contain apolipoprotein E (see Fig. 21-2) are taken up by the remnant receptor, which may be an LDL-receptor-related protein, in the liver. Free cholesterol is liberated intracellularly after attachment to the remnant receptor. Chylomicrons also function to deliver dietary triglyceride to skeletal muscle and adipose tissue. During the catabolism of nascent chylomicrons to remnants, triglyceride is converted to free fatty acids and apolipoproteins A-I, A-II, A-IV (free in plasma), C-I, C-II, and... 

Apolipoprotein C-II (apoC-II) The apolipoprotein on the surface of chylomicrons and very-low-density lipoproteins (VLDLs) that binds to and activates lipoprotein lipase. 

MacPhee, C. A., Howlett, G. J., Sawyer, W. H. and Clayton, A. H. A. 1999, Flelix-Helix Association of a Lipid-Bound Amphipathic a-Helix Derived from Apolipoprotein C-II. Biochemistry 38, 10878-10884. 

Apolipoprotein A-I Apolipoprotein A-II Apolipoprotein A-IV Apolipoprotein B-lOO Apolipoprotein B-48 Apolipoprotein C-I Apolipoprotein C-II Apolipoprotein C-III Apolipoprotein C-IV Apolipoprotein D Apolipoprotein E Apolipoprotein F Apolipoprotein H Apolipoprotein J (Clusterin) Apolipoprotein(a)... 

The prediction has been made that increases in the fractional volume occupancy of macromolecules in a physiological fluid should non-specifically accelerate the formation of amyloid by any amyloidogenic protein. Hatters et al. (2002) have looked at the effect of dextran TIO solutions on amyloid formation by human apolipoprotein C-II. The dextran was shown by analytical sedimentation equilibria studies not to form heterocomplexes with the apoC-n and nor was it incorporated into any of the amyloid fibrils studied. 

Hatters DM, Minton AP, Hewlett GJ (2002) Macromolecular crowding accelerates amyloid formation by human apolipoprotein C-II. J Biol Chem 277 7824-7830 He Y, Zhou H, Tang H, Luo Y (2006) Deficiency of disulfide bonds facilitating fibrillogenesis of endostatin. J Biol Chem 281 1048-1057... 

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