Plasma lipoprotein lipase

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. 

G3. Ganesan, D., Bradford, R. H., Ganesan, W., McConathy, W. J., Alaupovic, P., and Hazzard, W. R., Substrate specificity and polypeptide activation of postheparin plasma lipoprotein lipase in type III hyperlipoproteinemia (broad disease). CireukUion 46, Suppl. II, 248 (1972). 

Henriksen EL, Petersen PH, Beck-Nielsen H, Horder M (2001) Calibration, specificity and trueness of a postheparin plasma lipoprotein lipase assay. Clin Chem Lab Med 39 263-269... 

Possible physiological inhibitors of plasma lipoprotein lipase have been reported in plasma (Hollett and Meng, 1957), platelets (Hollett and Nestel, 1960), and white blood cells (Fekete et al., 1958). Their exact functional role remains to be established. Inhibition of plasma lipoprotein lipase activity has also been reported in pathological conditions, such as experimental pancreatitis (Kessler et al., 1962), clinical pancreatitis (Kessler et al., 1963), and idiopathic hyperlipemia (Klein and Lever, 1957). Several agents have been found to inhibit plasma lipoprotein lipase activity protamine and toluidine blue (Brown, 1952 Bragdon and Havel, 1954), Triton WR-1339 (Schotz et al., 1957), Triton A-20 and Tween 80 (Kellner et al., 1951), pituitary extracts (Rudman and Seid-... 

Heparins and heparinoids form complexes with proteins and bases, and as shown by the ability to produce metachromasia with submicro quantities are very effective complexing agents in trace amounts. Hence, these substances in trace amounts affect many biological agents such as enzymes, etc. When heparin or a heparinoid is injected in animal or man, an enzyme appears in the blood plasma, lipoprotein lipase. When an oil emulsion is incubated with varying amounts of blood plasma obtained after injection of heparin, the oil is cleared. The heparin has caused the release of this enzyme from tissues to the blood. Heparin and heparinoids have a pronounced action on many enzymes - proteolytic enzymes, carbohydrases, etc. and may inhibit, activate. 

POSTHEPARIN PLASMA LIPOPROTEIN LIPASE AND HEPATIC TRIGLYCERIDE LIPASE ACTIVITIES IN GOUT... 

Many studies have reported that gouty patients were associated frequently with hypertriglyceridemia(1). In the present study, postheparin plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (H-TGL) activities in gouty subjects were measured. 

T.Mrase, N.Yamada, N.Ohsawa, K.Kosaka, S.Morita, and S.Yoshida, Decline of postheparin plasma lipoprotein lipase in acromegalic patients. 

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. 

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. 

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. 

Gl. Ganesan, D., and Bradford, R. H., Isolation of apolipoprotein-free lipoprotein lipase from human post-heparin plasma. Biochem. Biophys. Res. Commun. 43, 544-549 (1971). 

Heparin also enhances lipoprotein lipase release (which clears plasma of circulating lipids), increases circulating free fatty acids, and reduces lipoprotein levels. Pharmacokinetics ... 

Partial summary of lipoprotein metabolism in humans. I to VII are sites of action of hypolipidemic drugs. I, stimulation of bile acid and/or cholesterol fecal excretion II, stimulation of lipoprotein lipase activity III, inhibition of VLDL production and secretion IV, inhibition of cholesterol biosynthesis V, stimulation of cholesterol secretion into bile fluid VI, stimulation of cholesterol conversion to bile acids VII, increased plasma clearance of LDL due either to increased LDL receptor activity or altered lipoprotein composition. CHOL, cholesterol IDL, intermediate-density lipoprotein. 

D. Lipoprotein lipase. Fenohbrate is a hypotriglyc-eridemic drug that lowers plasma triglycerides by increasing the activity of hpoprotein lipase, the enzyme responsible for disassembly of triglycerides in serum lipoproteins (VLDL, IDL and chylomicrons). 

Relevant heparin-binding enzymes not involved in the coagulation cascade are, for example, elastase, cathepsin G, superoxide dismutase, lipoprotein lipase and other lipases. The plasma clearing properties of heparin are associated with its binding to lipoprotein lipase and hepatic lipase when the enzymes are released from the surface of endothelial cells [11] and have been studied in view of a potential impact on the regulation of atherosclerosis. 

Mechanism of Action An antihyperlipidemic that enhances synthesis of lipoprotein lipase and reduces triglyceride-rich lipoproteins and VLDLs. Therapeutic Effect Increases VLDL catabolism and reduces total plasma triglyceride levels. Pharmacokinetics Well absorbed from the GI tract. Absorption increased when given with food. Protein binding 99%. Rapidly metabolized in the liver to active metabolite. Excreted primarily in urine lesser amount in feces. Not removed by hemodialysis. Half-life 20 hr. 

---