Lipase plasma

Figure 7.14 Regulation of rate of fatty acid oxidation in tissues. Arrows indicate direction of change (i) Changes in the concentrations of various hormones control the activity of hormone-sensitive lipase in adipose tissue (see Figure 7.10). (ii) Changes in the blood level of fatty acid govern the uptake and oxidation of fatty acid, (iii) The activity of the enzyme CPT-I is controlled by changes in the intracellular level of malonyl-CoA, the formation of which is controlled by the hormones insulin and glucagon. Insulin increases malonyl-CoA concentration, glucagon decrease it. Three factors are important TAG-lipase, plasma fatty acid concentration and the intracellular malonyl-CoA concentration.

Triacylglycerols must be hydrolyzed by a lipase to their constiment fatty acids and glycerol before further catab-ohsm can proceed. Much of this hydrolysis (hpolysis) occurs in adipose tissue with release of free fatty acids into the plasma, where they are found combined with semm albumin. This is followed by free fatty acid uptake into tissues (including hver, heart, kidney, muscle, lung, testis, and adipose tissue, but not readily by brain), where they are oxidized or reesterified. The uti-hzation of glycerol depends upon whether such tissues... 

HDL concentrations vary reciprocally with plasma triacylglycerol concentrations and directly with the activity of lipoprotein lipase. This may be due to surplus surface constituents, eg, phospholipid and apo A-I being released during hydrolysis of chylomicrons and VLDL and contributing toward the formation of preP-HDL and discoidal HDL. HDLj concentrations are inversely related to the incidence of coronary atherosclerosis, possibly because they reflect the efficiency of reverse cholesterol transport. HDL, (HDLj) is found in... 

Figure 25-5. Metabolism of high-density lipoprotein (HDL) in reverse cholesteroi transport. (LCAT, lecithinxholesterol acyltransferase C, cholesterol CE, cholesteryl ester PL, phospholipid A-l, apolipoprotein A-l SR-Bl, scavenger receptor B1 ABC-1, ATP binding cassette transporter 1.) Prep-HDL, HDLj, HDL3—see Table 25-1. Surplus surface constituents from the action of lipoprotein lipase on chylomicrons and VLDL are another source of preP-HDL. Hepatic lipase activity is increased by androgens and decreased by estrogens, which may account for higher concentrations of plasma HDLj in women.

Heparin is an important anticoagulant. It binds with factors IX and XI, but its most important interaction is with plasma antithrombin III (discussed in Chapter 51). Heparin can also bind specifically to lipoprotein lipase present in capillary walls, causing a release of this enzyme into the circulation. 

Superko, H., Bortz, W., Williams, P., Albers, J. and Wood, P., Caffeinated and decaffeinated coffee effects on plasma lipoprotein cholestrol, apolipoprotiens and lipase activity A controlled, randomized trial. American Journal of Clinical Nutrition 54, 599-605, 1991. 

J5. Jaume, J. C., Mendel, C. M Frost, P. H., Greenspan, F. S and Laughton, C. W., Extremely low doses of heparin release lipase activity into plasma and can thereby cause artifactual elevations in serum free thyroxine concentration as measured by equilibrium dialysis. Thyroid 6, 79-84 (1996). 

Chiesa G, Michelagnoli S, Cassinotti M, Gianfranceschi G, Werba JP, Paz-zucconi F, et al. Mechanisms of high-density lipoprotein reduction after probu-col treatment changes in plasma cholesterol esterification/transfer and lipase activities. Metabolism 1993 42 229-235. 

Guerra R, Wang J, Grundy SM, Cohen JC. A hepatic lipase (LIPC) allele associated with high plasma concentrations of high density lipoprotein cholesterol. Proc Natl Acad Sci USA 1997 94 4532-4537. 

Koseki M, Tsuji K, Nakagawa Y, Kawamura M, Ichikawa T, Kazama M, Kitabatake N and Doi E. 1989. Effects of gum Arabic and pectin on die emulsification, the lipase reaction and die plasma cholesterol... 

Familial lipoprotein lipase deficiency is characterized by a massive accumulation of chylomicrons and a corresponding increase in plasma triglycerides or a type I lipoprotein pattern. Presenting manifestations include repeated attacks of pancreatitis and abdominal pain, eruptive cutaneous xanthomatosis, and hepatosplenomegaly beginning in childhood. Symptom severity is proportional to dietary fat intake, and consequently to the elevation of chylomicrons. Accelerated atherosclerosis is not associated with this disease. 

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. 

Sandholzer, C., Feussner, G., Brunzell, J., and Utermann, G., Distribution of apolipopro-tein(a) in the plasma from patients with lipoprotein lipase deficiency and with type III hyperlipoproteinemia. J. Clin. Invest. 90, 1958-1965 (1992). 

Mitchell RJ, Earl L, Bray P, Fripp YJ, Williams J. DNA polymorphisms at the lipoprotein lipase gene and their association with quantitative variation in plasma high-density lipoproteins and triacylglycerides. Human Biology 1994 66 38397. 

T. Tsujita, H. Okuda, Fatty Acid Ethyl Ester-Synthetizing Activity of Lipoprotein Lipase from Rat Postheparin Plasma , J. Biol. Chem. 1994, 269, 5884-5889. 

A further group of AT-[(acyloxy)methyl] pro-moieties contains acidic and/or lipid-like substituents. Here again, most published results concern phenytoin. Thus, some phenytoin-lipid conjugates such as 8.183 and 8.186 (with R = various fatty acyl moieties) were reported [233]. Such prodrugs are, of course, insoluble in water but formed dispersions when briefly sonicated in EtOH/water mixtures containing sodium taurodeoxycholate. No significant hydrolysis was seen in buffer or plasma. In contrast, incubation with pancreatic lipase yielded the bis-deacyl derivatives (i.e., 8.182 and 8.185, respectively), with subsequent liberation of phenytoin the time for 50% liberation of phenytoin varied from 20 to 200 min under the conditions of the studies [233][234], The intermediates 8.182, 8.184, and 8.185 were also substrates for human and rat plasma hydrolases. 

G. K. E. Scriba, Phenytoin-Lipid Conjugates Chemical, Plasma Esterase-Mediated, and Pancreatic Lipase-Mediated Hydrolysis in vitro, Pharm. Res. 1993, 10, 1181 — 1186. 

Rare genetic absence of lipoprotein lipase results in excess triglyceride in the blood and its deposition in several tissues, including liver, skin, and pancreas. Orange-red eruptive xanthomas over the mucous membranes and skin may be seen. Abdominal pain and acute pancreatitis may occur. Fasting chylomicronemia produces a milky turbidity in the serum or plasma. 

Figure 7.10 Hormones that regulate the activity of the hormone-sensitive lipase in adipose tissue. Each hormone binds to a receptor on the outside of the plasma membrane and changes the activity of the lipase within the adipocyte, via a messenger molecule (Chapter 12). A hormone - independent lipase is also present with provides a low rate of release of fatty acid when the former is inactive.

In adipose tissue, the increased concentration of cyclic AMP activates the hormone-sensitive lipase to increase the rate of Upolysis and hence fatty acid release from adipose tissue. This increases the plasma level of fatty acids and hence their oxidation by muscle (see Chapter 7). 

The degradation of fats (lipolysis) is catalyzed in adipocytes by hormone-sensitive lipase [2]—an enzyme that is regulated by various hormones by cAMP-dependent interconversion (see p. 120). The amount of fatty acids released depends on the activity of this lipase in this way, the enzyme regulates the plasma levels of fatty acids. 

Selected entries from Methods in Enzymology [vol, page(s)] Detergent-resistant phospholipase Ai from Escherichia coll membranes, 197, 309 phospholipase Ai activity of guinea pig pancreatic lipase, 197, 316 purification of rat kidney lysosomal phospholipase Ai, 197, 325 purification and substrate specificity of rat hepatic lipase, 197, 331 human postheparin plasma lipoprotein lipase and hepatic triglyceride lipase, 197, 339 phospholipase activity of milk lipoprotein lipase, 197, 345. 

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