Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.34 (lipoprotein lipase)
7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An assay procedure using three different methods to recover lipoprotein lipase (LPL) activity from biopsy specimens of human adipose tissue has been developed. Elution of enzyme from small pieces of tissue was performed at 4 and 37 degrees C using a physiological buffer containing heparin and serum. Extraction of enzyme from a tissue homogenate was carried out in the presence of detergent (sodium deoxycholate and Nonidet P-40), which markedly improved the recovery of enzyme activity. It is suggested that elution at 4 degrees C represents extracellular enzyme activity only and therefore theoretically is the closest measure of physiologically active LPL on vascular endothelium, whereas elution at 37 degrees C, in addition, reflects some intracellular enzyme secreted during the incubation period. In female subjects of various relative body weights activity eluted at 37 degrees C as well as detergent-extracted activity were highly correlated with the extracellular activity eluted at 4 degrees C (r = 0.9). Furthermore, all three parameters correlated strongly with LPL activity in post-heparin plasma, suggesting that they are valid indices of physiologically active LPL. The regression of LPL activity in plasma after a 60-min heparin infusion on adipose tissue LPL yielded higher correlation coefficients for activities recorded after elution at 4 and 37 degrees C (r = 0.725 and 0.754, respectively) than for detergent extraction (r = 0.607). Moreover, the increment of adipose tissue LPL after feeding was approximately twice as high for the activity eluted at 4 and 37 degrees C (34%) as for detergent-extracted activity (19%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human adipose tissue lipoprotein lipase: changes with feeding and relation to postheparin plasma enzyme. 401 55

Mobilization of triacylglycerol stored in heart cells is accomplished by the combined action of lysosomal (acid) lipase and microsomal monoacylglycerol lipase or carboxylesterase. Non(heparin)-releasable neutral or alkaline lipase is similar to non(readily)-releasable lipoprotein lipase (LPL). The enzyme is mainly localized extracellularly. Non(readily)-releasable LPL probably represents LPL in caveola or vacuolae of vascular endothelium and/or LPL on myocardial interstitium. It contributes to the uptake of lipoprotein constituents in heart cells. Glycerol, an endproduct of lipolysis, is not a reliable marker for the net mobilization of lipid stored in heart cells. It is formed both intra- and extracellularly, and does not reflect the rate of oxidation of part of free fatty acids formed.
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PMID:Localization and function of myocardial lipolysis. 647 80

This article reviews the experimental and clinical evidence regarding heparin therapy in the prophylaxis of coronary heart disease. The actions of heparin take place at the vascular endothelium where injected heparin concentrates, and within the bloodstream. At the endothelium heparin acts to prevent endothelial injury, prevent thrombin generation, prevent platelet adhesion to endothelium, and to decrease uptake of serum lipoproteins. Within the bloodstream heparin increases lipoprotein lipase activity and reduces the concentration of atherogenic very low-density lipoproteins. The reduction in lipemia enhances oxygen transfer from blood to the tissues, and decreases thrombin or ADP-induced platelet aggregation. Heparin increases the concentration of high-density lipoproteins. It decreases hypercoagulability and inhibits overactivation of serum complement. Heparin reduced atherosclerosis in most studies in cholesterol-fed animals. In human subjects who had a myocardial infarct at least one year before the onset of treatment, long-term intermittent heparin therapy significantly decreased cardiovascular deaths as compared to control groups.
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PMID:Heparin and atherosclerosis. A review of old and recent findings. 698 41

Radioiodinated lipoprotein lipase, isolated from bovine milk (125I-labeled milk lipoprotein lipase) was shown to retain full hydrolytic activity towards its native substrate, i.e., chylomicron triacylglycerol. The 125I-labeled enzyme interacted with various cells in culture by being bound to the cellular surface, internalized and degraded. Cellular binding of the labeled enzyme occurred in the presence or absence of substrate and was related to enzyme concentration. Heparin reduced cellular binding by 50% but inhibited uptake and degradation more extensively. Cellular uptake was not affected by chloroquine or NH4Cl, but degradation of the labeled enzyme was blocked. Uptake and degradation were not inhibited by mannose 6-phosphate. The interaction between the exogenous enzyme and cells which do not synthesize lipoprotein lipase, i.e., fibroblasts and endothelial cells, resulted in a high ratio of surface binding to degradation. In heart cell cultures and preadipocyte cultures, which produce lipoprotein lipase, the ratio of enzyme catabolized to that bound was high at all time points examined. Since in the intact organism lipoprotein lipase acts at the luminal surface of vascular endothelium, it seems expedient that these cells are able to bind the enzyme, but will catabolize it only slowly. The rapid and extensive degradation of the 125I-labeled lipoprotein lipase in heart cells and preadipocytes may be related to the metabolism of the endogenously produced lipoprotein lipase.
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PMID:Fate of milk 125I-labelled lipoprotein lipase in cells in culture. Comparison of lipoprotein lipase- and non-lipoprotein lipase-synthesizing cells. 706 65

The very low density lipoprotein (VLDL) receptor binds apolipoprotein E-rich lipoproteins as well as the 39-kDa receptor-associated protein (RAP). Ligand blotting experiments using RAP and immunoblotting experiments using an anti-VLDL receptor IgG detected the VLDL receptor in detergent extracts of human aortic endothelial cells, human umbilical vein endothelial cells, and human aortic smooth muscle cells. To gain insight into the role of the VLDL receptor in the vascular endothelium, its ligand binding properties were further characterized. In vitro binding experiments documented that lipoprotein lipase (LpL), a key enzyme in lipoprotein catabolism, binds with high affinity to purified VLDL receptor. In addition, urokinase complexed with plasminogen activator-inhibitor type I (uPA.PAI-1) also bound to the purified VLDL receptor with high affinity. To assess the capacity of the VLDL receptor to mediate the cellular internalization of ligands, an adenoviral vector was used to introduce the VLDL receptor gene into a murine embryonic fibroblast cell line deficient in the VLDL receptor and the LDL receptor-related protein, another endocytic receptor known to bind LpL and uPA.PAI-1 complexes. Infected fibroblasts that express the VLDL receptor mediate the cellular internalization of 125I-labeled LpL and uPA.PAI-1 complexes, leading to their degradation. Non-infected fibroblasts or fibroblasts infected with the lacZ gene did not internalize these ligands. These studies confirm that the VLDL receptor binds to and mediates the catabolism of LpL and uPA.PAI-1 complexes. Thus, the VLDL receptor may play a unique role on the vascular endothelium in lipoprotein catabolism by regulating levels of LpL and in the regulation of fibrinolysis by facilitating the removal of urokinase complexed with its inhibitor.
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PMID:The very low density lipoprotein receptor mediates the cellular catabolism of lipoprotein lipase and urokinase-plasminogen activator inhibitor type I complexes. 759 75

Each day more than 150 g of triglycerides are transported from the intestine in chylomicrons and from the liver in VLDL. The triglycerides are hydrolyzed by lipoprotein lipase at the vascular endothelium in extrahepatic tissues. This releases fatty acids and monoglycerides which can move across aqueous barriers and cell membranes to reach metabolic sites in tissue cells. At the endothelial cell the enzyme is anchored to heparin sulfate proteoglycans. The enzyme is located in a position where it can freely interact with lipoproteins from the circulating blood. The hydrolysis is a rapid and efficient process. A chylomicron containing more than a million triglyceride molecules can be unloaded in less than 10 minutes. As a consequence of triglyceride hydrolysis the lipoproteins are reduced to remnant particles. Some of these are rapidly removed from plasma but some are remodeled into LDL and HDL, lipoproteins that are catabolized slowly and therefore dominate in plasma. The activity of LPL is regulated in a tissue-specific manner and this directs the destination of triglyceride transport. The enzyme binds fatty acids which provides a mechanism for product control of the reaction. When the tissue can no longer assimilate the fatty acids, the lipase reaction is stopped and the lipoprotein returns to the circulating blood. In addition to its catalytic action, lipoprotein lipase can also serve as a ligand for binding of lipoproteins to cell surfaces and to receptors. Hence, the lipase has a dual role in lipoprotein metabolism, mediating both unloading of triglycerides in extrahepatic tissues and particle catabolism in the liver.
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PMID:[The great Scandinavian Medical Jahre Prize 1994. Role of lipoprotein lipase in lipoprotein metabolism]. 783 Nov 8

Catabolism of triglyceride-rich lipoproteins, including chylomicrons (CM), is reduced in the nephrotic syndrome. It has been suggested that hyperlipidemia per se might lead to reduced CM catabolism by saturating catabolic sites. Evidence also implicates disordered high-density lipoprotein function as reducing the activity of lipoprotein lipase (LPL), the final effector of CM lipolysis. To establish whether CM lipolysis would be abnormal in the absence of either abnormal rat lipoproteins or hyperlipidemia, we measured CM lipolysis by isolated perfused hearts of rats with passive Heymann nephritis. We found that lipolysis was significantly reduced by 30% at 30 minutes (246 +/- 40 mumol v 164 +/- 10 mumol fatty acid released/hr, P < 0.05). Uptake of fatty acids was also significantly less in nephrotic hearts than in control hearts (7.25% +/- 0.93% of dose v 3.32% +/- 0.011% of dose, P < 0.01). Total heart LPL activity was reduced by 40% in hearts of nephrotic animals (368.5 +/- 39.4 mumol v 210.6 +/- 25.9 mumol free fatty acid released/hr/g heart, P < 0.01). The heparin-releasable LPL pool is that pool bound to the vascular endothelium and represents the biologically active fraction. We perfused hearts with heparin and found that heparin-releasable LPL was reduced by an order of magnitude in hearts from nephrotic rats (173 +/- 33 mumol v 19.4 +/- 11.7 mumol free fatty acid released/hr/heart, P < 0.001). The decrease in this pool represented nearly entirely the difference in total heart LPL in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Defective lipolysis persists in hearts of rats with heymann nephritis in the absence of nephrotic plasma. 832 75

Free fatty acids released through hydrolysis of triacylglycerols by lipoprotein lipase at the vascular epithelium may act in feedback control of lipoprotein lipase activity.
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PMID:Free fatty acids in plasma may exert feed-back control of lipoprotein lipase activity. 844 4

Xanthine oxidoreductase (XDH + XO, EC 1.2.3.2) is released into the circulation from organs rich in XO activity. Herein we report the specific high affinity binding of XO to glycosaminoglycans (GAGs) and the preferential association of XO with heparin, compared with heparan sulfate, chondroitin sulfate, and dematan sulfate. The binding of XO to Sepharose 6B-conjugated heparin (HS6B) occurs at physiological ionic strength and increased with pH, with Scatchard analysis revealing a nonlinear binding pattern at pH 7.4. The dissociation constant (Kd) for XO binding was 0.4 to 1.8 x 10(-7) M, similar to the heparin-reversible binding of lipoprotein lipase to vascular endothelium. The binding energy of 9-13 kcal/mol was concordant with noncovalent electrostatic interactions. Xanthine oxidase immobilization to HS6B rendered a catalytically active enzyme from that had kinetic characteristics distinct from XO in free solution. While the Km and Ki for xanthine in phosphate buffer at pH 7.4 were 3 microM and 1.6 mM, respectively, for free XO, they were 15 microM and 2.8 mM for immobilized XO. Inhibition constants for guanine and uric acid were also increased upon XO binding to HS6B. Changes in kinetic parameters were related to a real and not apparent decrease in binding affinity for substrate and inhibitors and were not due to diffusion-controlled processes within the gel matrix. Changes in Km and Ki for xanthine also had a significant influence on the relative quantities of O2.- and H2O2 generated by a given substrate concentration. Superoxide formed by HS6B-bound XO was partially consumed within the gel microenvironment which electrostatically excluded CuZn SOD. Immobilization of XO increased the half-life of enzyme activity in buffer and in the absence of substrate from 67 to 120 h at 4 degrees C. These data indicate that binding to cell surfaces will strongly influence the catalytic properties, oxidant producing capacity, and stability of XO.
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PMID:Xanthine oxidase binding to glycosaminoglycans: kinetics and superoxide dismutase interactions of immobilized xanthine oxidase-heparin complexes. 905 42

An increased adherence of leukocytes to the vascular endothelium appears to be a crucial event in the development of atherosclerosis. The role of endothelial cell adhesion molecules is gaining increasingly interest in this context. Several studies show an influence of lipoproteins, especially low-density-lipoproteins on adhesion molecule stimulation. The aim of our study was to analyze the atherogenic potential of postprandially elevated serum triglyceride levels by investigating the impact of postprandial lipoproteins (chylomicrons (CH, isolated 4 h after a standard oral lipid load)) on the expression of E-selectin (endothelial leukocyte adhesion molecule-1, ELAM-1) and VCAM-1 (vascular cell adhesion molecule-1). In addition we used chylomicrons that had been incubated with lipoprotein lipase (50 U/ml) for 3 h (CH-LPL). The endotoxin lipopolysaccharide (LPS) served as positive control for adhesion molecule stimulation. Human umbilical vein endothelial cells (HUVEC) were incubated with the samples for 4 h and expression of E-Selectin and VCAM-1 was determined by ELISA. The expression of E-selectin was induced by LPS (530 +/- 64% compared to the basal activity (= 100%)) and by CH (342 +/- 94%); CH-LPL had no effect on E-Selectin expression. VCAM-1 expression was stimulated by LPS (395 +/- 221%) and similarly by CH-LPL (322 +/- 136%) but considerably stronger by CH (1245 +/- 324). In summary, chylomicrons induced an enhancement of the expression of both adhesion molecules, which closely resembled or even exceeded the endotoxin-induced stimulation. Interestingly, this effect was diminished or even reversed after incubation with LPL.
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PMID:Chylomicrons induce E-selectin and VCAM-1 expression in endothelial cells. 928 41


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