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)

A radiochemical method for selective measurement of postheparin lipase activities was adapted to analyze lipoprotein lipase and hepatic lipase in preheparin plasma. The assay sensitivity was increased about four-fold by doubling both the volume of plasma used and the volume of lipolytic products taken for liquid scintillation counting, and was further improved by increasing the incubation period by 50% to 90 min. Rabbit antiserum to human hepatic lipase was unsuitable for the selective measurement of lipoprotein lipase because of apparent endogenous lipolytic activity. Preheparin hepatic lipase, however, was sensitive to inactivation by sodium dodecyl sulfate (SDS), the inhibition being greatest (> 90%) for plasma incubated with an equal volume of 40 mmol/L SDS. Intra- and interassay CVs for the two enzymes were 12.5-14.6% and 17.4-19.7%, respectively. In a cross-sectional study of 84 healthy subjects, pre- and postheparin hepatic lipase activities were higher in men than women, were correlated with indices of obesity, and were significantly correlated with one another, which explained the association of the former with plasma concentrations of high-density lipoprotein (HDL), HDL2, and small, dense low-density lipoproteins. There was no significant relationship between pre- and postheparin lipoprotein lipase activities, but the former were correlated with plasma concentrations of free fatty acids (FFA) and very-low-density lipoprotein. Apparently, preheparin activities of hepatic lipase, but not of lipoprotein lipase, may be a useful measure of the physiological function of "whole body" enzyme activity in cross-sectional and metabolic studies, where heparinization is not possible. Preheparin lipoprotein lipase activities, however, may reflect displacement of the enzyme by FFA and subsequent binding to remnants of triglyceride-rich lipoproteins.
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PMID:Measurement and physiological significance of lipoprotein and hepatic lipase activities in preheparin plasma. 788 16

Lipoprotein lipase is the extrahepatic lipase responsible for the hydrolysis of triglycerides in chylomicrons and very low-density lipoproteins. Its enzymic activity and its location on the surface of endothelial cells are affected by the presence of fatty acids, implying that the protein possesses binding sites for that ligand. In this study, we examine the binding of fatty acids to LpL and describe factors that must be considered when the dissociation constant of the acceptor-ligand equilibrium is close to the critical micelle concentration of the fatty acid. The interaction of fatty acids with lipoprotein lipase (LpL) was studied by two methods. A new direct method, based on the LpL-induced increase in the apparent critical micelle concentration of the sodium soap of the fatty acid, indicates the presence of multiple high-affinity binding sites. In the second method, the specific binding of fatty acids to LpL was measured by quantitating the blue shift in the tryptophan fluorescence of LpL that occurs upon binding the ligand. Both methods suggest the existence of 4-6 fatty acid binding sites on LpL with a dissociation constant on the order of 10(-6)-10(-7) M. Further analysis of the blue shift indicates that at higher concentrations of fatty acid, large complexes are formed consisting of 260-310 molecules of fatty acid per LPL monomer. In contrast, no large complexes are formed with fatty acids that form crystals above their solubility limit.
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PMID:Interactions between fatty acids and lipoprotein lipase: specific binding and complex formation. 794 38

The three-dimensional structure of a synthetic fragment of human apolipoprotein CII (apo-CII) in 35%, 1,1,1,3,3,3-hexafluoro-2-propanol (HFP) has been determined on the basis of distance and intensity constraints derived from two-dimensional proton nuclear magnetic resonance measurements. The NOE crosspeak build-up rates were converted to distance constraints which were used in the distance geometry program DI-ANA. A set of one hundred structures were generated and of these ten structures were used in molecular dynamics simulations using the program XPLOR. This program enabled a direct minimization between the difference of the two-dimensional NOE intensities and those calculated from the full relaxation matrix. In this way spin diffusion is fully taken into account, which can be seen from the considerable improvement of the R-factor after the relaxation matrix refinement. These calculations show that this fragment, which corresponds to the carboxy terminal 30 amino acids of intact apo-CII and which retains its ability to activate lipoprotein lipase, is essentially flexible, but has three defined secondary structural elements. The most significant one is an alpha-helix between residues 67 and 74. The following three residues adopt a turn-like structure. Another turn of alpha-helix is seen between residues 56 and 59. The effect of the solvent system on the secondary structure was studied by circular dichroism spectroscopy. The results show that the mixed aqueous 35% HFP solvent induces secondary structure of a very similar nature to the one induced by sodium dodecyl sulphate.
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PMID:A refined three-dimensional solution structure of a carboxy terminal fragment of apolipoprotein CII. 811 21

The genetic and environmental determinants of hypertension, lipid abnormalities, and coronary artery disease (CAD) have been studied for 15 years in Utah in population-based multigenerational pedigrees (2500 subjects among 98 pedigrees), twin pairs (74 monozygous and 78 dizygous), hypertensive siblings (131 sibships), siblings with CAD before age 55 (45 sibships), and anecdotally ascertained pedigrees with type II diabetes (271 subjects among 16 pedigrees), lipoprotein lipase deficiency (106 subjects in a single pedigree), and familial hypercholesterolemia (502 heterozygotes among 50 pedigrees). Estimates of heritability ranged from 20 to 75% for blood pressures and blood lipids. A strong positive family history predicts a future occurrence of hypertension (relative risk [RR] = 3.8) and CAD (RR = 12.7). Segregating single-gene effects were found for several 'intermediate phenotypes' associated with hypertension (erythrocyte sodium-lithium countertransport, intraerythrocytic sodium, a relative fat pattern, total urinary kallikrein excretion, and fasting insulin levels). Strong single-gene effects in segregation analysis were also found for low-density lipoprotein (LDL) cholesterol, lipoprotein (a) (Lp[a]), low high-density lipoprotein (HDL) cholesterol, and high apolipoprotein (apo) B. Deoxyribonucleic acid (DNA) markers of lipid abnormalities or hypertension have included LDL-receptor defects, lipoprotein lipase deficiency, high Lp(a), familial defective apo B, decreased quantitative levels of apo B, apo E phenotype, angiotensinogen, and 'glucocorticoid remediable aldosteronism (GRA) hypertension.' Also tested in Utah studies, but not found to be DNA markers for hypertension, were the genetic loci for the structural genes for renin and angiotensin-converting enzyme, and the sodium antiport system. In addition, important gene-gene interactions (LDL receptor with apo E2) and gene-environment interactions (kallikrein with potassium intake) were found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Genetic basis of familial dyslipidemia and hypertension: 15-year results from Utah. 829 39

Milk component 3 was an inhibitor of lipoprotein lipase activity responsible for spontaneous lipolysis occurring in milk stored at 4 degrees C. Experiments using a pH-stat apparatus and emulsified tributyrin showed that component 3 inhibited porcine pancreatic lipase. The lipolytic activity was fully restored by addition of sodium taurodeoxycholate and colipase to the emulsion containing component 3. Inhibition did not seem to be the result of a direct interaction between component 3 and the enzyme. Component 3 had a strong adsorption power superior to that of pancreatic lipase, as shown by tensiometric measurements at an n-tetradecane-water interface. Lipase inhibition by component 3 could be the consequence of a rapid diffusion and preferential adsorption of component 3 at the oil-water interface provoking an important decrease of interfacial tension and avoiding the adsorption of lipase.
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PMID:Study of mechanism of lipolysis inhibition by bovine milk proteose-peptone component 3. 840 64

Sensitive, reliable procedures are reported for the selective assay of lipoprotein lipase (LPL) and hepatic lipase (HL) in postheparin plasma samples. LPL is inhibited in the HL assay by inclusion of 0.76 mol/L sodium chloride in the substrate. In the LPL assay, specificity is attained by pretreating the sample with sodium dodecyl sulfate, which selectively denatures HL. This LPL method was validated by direct comparison with a procedure in which HL is inactivated by an antiserum to human HL. We used the described assays to quantify LPL and HL activity in 32 normal adults, demonstrating a clear sex difference for both enzymes. On average, the men displayed higher HL and lower LPL activities than did the women.
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PMID:Hepatic and lipoprotein lipases selectively assayed in postheparin plasma. 843 9

Bovine aortic smooth muscle cells and human skin fibroblasts were incubated with beta-very low density lipoprotein (beta VLDL) isolated from cholesterol-fed rabbits and labeled with [3H]cholesteryl oleate. Addition of lipoprotein lipase resulted in a 3.2-4.8-fold increase in cell associated radioactivity of which 45-61% was in free cholesterol, i.e., derived after intracellular hydrolysis. After exposure of smooth muscle cells to beta VLDL for up to 9 days and 60 min sodium heparin wash at 4 degrees C to remove extracellular surface bound lipoprotein, cellular cholesterol increase was 2 micrograms in controls and in the presence of lipoprotein lipase (LPL) it was tenfold higher. Addition of [3H]cholesteryl ester labeled beta VLDL during the last 48 h of incubation showed that 30-40% of total cellular label was in free cholesterol. This value represents the minimal cellular uptake of the added lipoprotein cholesteryl ester. Addition of recombinant apolipoprotein (apo) E to smooth muscle cells incubated with beta VLDL and [3H]oleate induced no further increase in [3H]cholesteryl oleate. We propose that following LPL-mediated binding of beta VLDL to heparan sulphate, this complex either undergoes endocytosis, or translocation of cholesteryl ester into the smooth muscle cells (SMC) occurs without endocytosis of the entire particle. The present results indicate that in the aortic wall macrophage-derived lipoprotein lipase could play a role in cholesteryl ester accretion in smooth muscle cells during atherogenesis.
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PMID:Can lipoprotein lipase be the culprit in cholesteryl ester accretion in smooth muscle cells in atheroma? 846 Oct 56

We evaluated the pharmacokinetics of IV administered sodium heparin and the pharmacodynamic effect of heparin on lipoprotein lipase (LPL) activity. Horses were allotted to 3 groups. Plasma samples were obtained from each horse before and at various times for 6 hours after heparin administration for determination of heparin concentration, LPL activity, and activated partial thromboplastin time (APTT). The disposition of heparin was dose dependent. The area under the plasma heparin concentration vs time curve (AUC) increased more than proportionally with dose, indicating that heparin elimination was nonlinear. Total clearance of heparin was similar after the 40 and 80 IU/kg of body weight dosages, averaging 0.45 and 0.36 IU/kg/min, respectively. However, after administration of the 120 IU/kg dose, clearance was significantly less than that after the 40 IU/kg dose. The half-life of heparin averaged 53, 70, and 136 minutes after 40, 80, and 120 IU/kg, respectively, with significant differences observed between the low and high doses. In contrast to heparin, the area under the plasma concentration vs time curve for LPL activity increased less than proportionally with dose. Maximal LPL activity observed was independent of dose, averaging 4.8 mumol of free fatty acids/ml/h. The APTT was significantly prolonged for 120 minutes after administration of the 40 IU/kg dose. Correlation coefficients for LPL activity vs either plasma heparin concentration or APTT were less than 0.7, indicating that neither laboratory measure can be used to accurately predict plasma LPL activity.
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PMID:Pharmacokinetics of heparin and its pharmacodynamic effect on plasma lipoprotein lipase activity and coagulation in healthy horses. 853 79

Using ligand blotting techniques, with low-density lipoprotein (LDL) as ligand, we have previously described the existence of atypical lipoprotein-binding proteins (105 kDa and 130 kDa) in membranes from human aortic medical tissue. The present study demonstrates that these proteins are also present in membranes from cultured human (aortic and mesenteric) and rat (aortic) vascular smooth-muscle cells (VSMCs). To assess the relationship of 105 and 130 kDa lipoprotein-binding proteins to known lipoprotein receptors, ligand binding specificity was studied. We tested effects of substances known to antagonize ligand binding to either the LDL [apolipoprotein B,E (apo B,E)] receptor (dextran sulphate, heparin, pentosan polysulphate, protamine, spermine, histone), the scavenger receptor (dextran sulphate, fucoidin), the very-low-density-lipoprotein (VLDL) receptor [receptor-associated protein (RAP)], or LDL receptor-related protein (RAP, alpha 2-macroglobulin, lipoprotein lipase, exotoxin-A). None of these substances, with the exception of dextran sulphate, influenced binding of LDL to either 105 or 130 kDa proteins. Sodium oleate or oleic acid, known stimuli for the lipoprotein binding activity of the lipolysis-stimulated receptor, were also without effect. LDL binding to 105 and 130 kDa proteins was inhibited by anti-LDL (apo B) antibodies. LDL and VLDL bound to 105 and 130 kDa proteins with similar affinities (approximately 50 micrograms/ml). The unique ligand selectivity of 105 and 130 kDa proteins supports the existence of a novel lipoprotein-binding protein that is distinct from all other currently identified LDL receptor family members. The similar ligand selectivity of 105 and 130 kDa proteins suggests that they may represent variant forms of an atypical lipoprotein-binding protein.
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PMID:Ligand selectivity of 105 kDa and 130 kDa lipoprotein-binding proteins in vascular-smooth-muscle-cell membranes is unique. 869 79

Phenylboronates are competitive inhibitors of serine. hydrolases including lipases. We studied the effect of m-aminophenylboronate on triglyceride-hydrolyzing activity of hepatic lipase (EC 3.1,1.3). m-Aminophenylboronate inhibited hepatic lipase activity with a Ki value of 55 microM. Furthermore, m-aminophenylboronate protected hepatic lipase activity from inhibition by di-isopropyl fluorophosphate, an irreversible active site inhibitor of serine hydrolases. Inhibition of hepatic lipase activity by m-aminophenylboronate was pH-dependent. The inhibition was maximal at pH 7.5, while at pH 10 it was almost non-existent. These data were used to develop a purification procedure for postheparin plasma hepatic lipase and lipoprotein lipase. The method is a combination of m-aminophenylboronate and heparin-Sepharose affinity chromatographies. Hepatic lipase was purified to homogeneity as analyzed on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The specific activity of purified hepatic lipase was 5.46 mmol free fatty acids h-1 mg-1 protein with a total purification factor of 14,400 and a final recovery of approximately 20%. The recovery of hepatic lipase activity in m-aminophenylboronate affinity chromatography step was 95%. The purified lipoprotein lipase was a homogeneous protein with a specific activity of 8.27 mmol free fatty acids h-1 mg-1. The purification factor was 23,400 and the final recovery approximately 20%. The recovery of lipoprotein lipase activity in the m-aminophenylboronate affinity chromatography step was 87%. The phenylboronate affinity chromatography step can be used for purification of serine hydrolases which interact with boronates.
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PMID:Inhibition of hepatic lipase by m-aminophenylboronate. Application of phenylboronate affinity chromatography for purification of human postheparin plasma lipases. 884 15


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