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)

Methods available for measurement of plasma lipoprotein-cholesterol concentrations and activities of lipoprotein lipase, hepatic lipase, lecithin:cholesterol acyl transferase (LCAT), and cholesteryl ester transfer protein were adapted for use in cats. A combined ultracentrifugation/precipitation procedure was used to isolate very low-density lipoproteins (VLDL), then to separate low-density lipoproteins (LDL) from high-density lipoproteins (HDL). The reagent used, 92 mM heparin-manganese chloride, provided complete precipitation of LDL with only trace and insignificant contamination by HDL. Efforts to selectively measure lipoprotein lipase activity in plasma, collected after IV injection of heparin, by inhibiting hepatic lipase with sodium dodecyl sulfate were unsuccessful, and the activity of this enzyme was calculated as the difference between total and hepatic lipase activities. The latter was measured in the presence of high salt concentration to inhibit lipoprotein lipase. Cholesterol esterifying activity was identified in feline plasma and was typical of LCAT, in that it was dependent on apolipoprotein A-I as a cofactor. The intra-assay and interassay coefficients of variation for measurement of lipoprotein lipase, hepatic lipase, and LCAT activities were 18.4, 4.6, and 7.2%, and 20.4, 10.7, and 5.3%, respectively. Appreciable cholesteryl ester transfer protein activity was not detected in either undiluted or diluted plasma. These methods were subsequently used to investigate the effects of pregnancy and lactation on lipoprotein metabolism in a group of 10 queens. Plasma concentrations of cholesterol and triglycerides were unaltered during pregnancy, but the concentrations of VLDL-cholesterol increased and those of HDL-cholesterol decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Development of methods for analyzing plasma lipoprotein concentrations and associated enzyme activities and their use to measure the effects of pregnancy and lactation in cats. 777 94

Cholesterol and triglyceride in the various lipoprotein fractions were determined in five patients without functional lipoprotein lipase (LPL) while on their habitual therapeutic diet of 'low fat' content (20-25 g/day). They were also studied following 3 days on either a 'minimal fat' diet (< 15 g/day) or a 'moderate fat' diet (45-50 g/day). Values obtained were compared with the respective levels measured in five control subjects on a 'normal fat' (70-90 g/day) diet. The patients had hypertriglyceridaemia (type V hyperlipoproteinaemia) under all dietary conditions. Cholesterol and triglyceride levels in plasma and in the chylomicron fraction increased in the patients with increasing dietary fat. In the very low density lipoprotein (VLDL) fraction from the patients, triglyceride levels also increased with the dietary fat intake, but cholesterol levels were similar under all dietary conditions. In the patients, cholesterol concentrations in the low (LDL) and high density (HDL) lipoprotein fractions were significantly lower than the respective levels in controls, but the ratio of cholesterol to triglyceride levels in both of these lipoprotein fractions decreased with the dietary fat intake. VLDL apolipoprotein B-100 (apo B-100) pool size was similar in the patients on the two test diets (P = 0.95) and 3.5-fold higher than in five healthy volunteers on a normal fat diet. Using a stable isotope enrichment method, the kinetics of apo B-100 were investigated in the patients under the last two dietary conditions. The fractional and absolute secretion rates of the apolipoprotein in the patients did not vary with fat intake, but fractional secretion rates were significantly lower and the absolute secretion rates were significantly higher in the patients than the respective values in the controls. These results are consistent with the hypothesis that in the absence of LPL activity the metabolism of chylomicron and VLDL particles in the circulation results in triglyceride-rich LDL and HDL particles that are taken up by the liver at increased rates, thus reducing the plasma LDL and HDL cholesterol concentrations, whereas the products of hydrolysis of these particles induce an increased rate of synthesis of triglyceride and an increased rate of secretion of VLDL apo B-100.
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PMID:Metabolism of apolipoprotein B-100 and of triglyceride-rich lipoprotein particles in the absence of functional lipoprotein lipase. 829 98

Plasma lipoproteins, plasma activities of lecithin:cholesterol acyltransferase (LCAT), phospholipid transfer protein (PLTP), cholesteryl ester transfer protein (CETP) and post-heparin lipases were measured before and after cholesterol challenge in two inbred strains of rabbits with either a high (hyper-responders) or a low (hyporesponders) response of plasma cholesterol to dietary cholesterol. The purpose of this study was to provide clues about the mechanisms underlying the effect of dietary cholesterol on lipoprotein levels and composition, and particularly those underlying the strain difference of this effect. Cholesterol feeding (0.15 g of cholesterol/100 g of diet) caused increased plasma total cholesterol concentrations and an increased ratio of cholesteryl esters:triacylglycerol in all lipoprotein particles in both strains; these effects were significantly greater in hyper- than hypo-responsive rabbits. Feeding on the high-cholesterol diet lowered plasma triacylglycerols in hyper-responders, but caused increased plasma triacylglycerol levels in hyporesponders. This was accompanied by significantly greater increases in the activities of hepatic triacylglycerol lipase and lipoprotein lipase in hyper- than in hypo-responders. Both strains showed a dietary-cholesterol-induced rise in plasma CETP as well as in PLTP activity. The increase in PLTP activity was greater in the hyper-responders, but that of CETP was less. There was no effect of dietary cholesterol on LCAT activity. It is hypothesized that the lipases are involved in the removal of cholesterol-rich lipoproteins.
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PMID:Plasma activities of lecithin:cholesterol acyltransferase, lipid transfer proteins and post-heparin lipases in inbred strains of rabbits hypo- or hyper-responsive to dietary cholesterol. 835 38

Hypertension and diabetes appear to increase coronary heart disease risk in part by causing an abnormality in lipid metabolism. Most affected are patients with familial dyslipidemic hypertension (FDH) and noninsulin-dependent diabetes mellitus (NIDDM). The lipid disorders most often encountered in these patients are increased levels of triglycerides, very low-density lipoprotein (VLDL) cholesterol, and small, dense low-density lipoprotein (LDL) cholesterol, and low levels of high-density lipoprotein (HDL) cholesterol. These abnormalities appear to result from increased hepatic secretion of VLDL particles due to increased concentrations of free fatty acids and glucose, reduced VLDL clearance due to reduced activity of lipoprotein lipase, and reduced LDL clearance due to glycosylation of ligand proteins. Treatment of the dyslipidemia associated with FDH should follow the guidelines from the National Cholesterol Education Program. Treatment in men and women with NIDDM should be considered when LDL cholesterol levels are 130 mg/dl or above, triglyceride levels are 200 mg/dl or above, or non-HDL cholesterol levels are 160 mg/dl or greater. Aggressive lifestyle changes should be initiated first, including weight loss in obese patients, control of glucose levels in those with NIDDM, avoidance of antihypertensive drugs that may worsen lipid levels in patients with FDH, and eating a diet restricting saturated fat and cholesterol. Addition of lipid-altering drugs should be considered if such changes do not achieve effective lipid control. The agent should be tailored to the patient's lipid profile, in general by using bile acid resins, niacin, or reductase inhibitors to lower LDL cholesterol and gemfibrozil or niacin to lower triglycerides. Niacin should be avoided in patients with NIDDM.
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PMID:Understanding and treating dyslipidemia associated with noninsulin-dependent diabetes mellitus and hypertension. 836 60

The presence of oxysterols in macrophages isolated from atherosclerotic tissue and the effect of oxysterols on the regulation of lipoprotein lipase (LPL) mRNA were studied. Both rabbit and human macrophages, freshly isolated from atherosclerotic aorta, show about the same distribution of oxysterols, analyzed by isotope dilution mass spectrometry, except that all three preparations of human arterial-derived macrophages contained high levels of 27-hydroxycholesterol, which was not found in rabbit macrophages. To determine if oxysterols regulate LPL expression, human monocyte-derived macrophages were incubated with different oxysterols. Incubation with 7 beta-hydroxycholesterol and 25-hydroxycholesterol resulted in a 70-75% reduction of LPL mRNA, analyzed by quantitative RT-PCR. Cholesterol and other tested oxysterols showed no effect on macrophage LPL mRNA expression compared with control. LPL activity in the medium was also reduced after exposure of the macrophages to 7 beta-hydroxycholesterol and 25-hydroxycholesterol. In conclusion, we have demonstrated accumulation of oxysterols in macrophage-derived foam cells isolated from atherosclerotic aorta. There was suppression of LPL mRNA in human monocyte-derived macrophages after incubation with 7 beta-hydroxycholesterol and 25-hydroxycholesterol. It is tempting to suggest that an exposure to oxysterols may explain our earlier observation of a low level of LPL mRNA in arterial foam cells.
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PMID:Oxysterols present in atherosclerotic tissue decrease the expression of lipoprotein lipase messenger RNA in human monocyte-derived macrophages. 856 68

A series of 3-amino-1-(2,3,4-mononitro-, mono-, or dihalo-phenyl)propan-1-ones were synthesized and shown to be effective in lowering both serum cholesterol and triglyceride levels significantly in CF1 mice and Sprague-Dawley rats. All analogs showed better activity than the standard drugs, lovastatin and clofibrate, in reducing the serum cholesterol and triglyceride levels in mice at 8 mg/kg/day intraperitoneally. The best active analogs, 3-morpholino-1(3-nitrophenyl)propan-1-one (4) and 3-piperidino-1-(3-nitrophenyl)propan-1-one (5), exhibited 58% and 67% reduction of serum cholesterol levels, respectively, and 42% and 46% reduction of serum triglyceride levels, respectively, after 16 days of administration at 8 mg/kg/day intraperitoneally in CF1 mice. In Sprague-Dawley rats at 8 mg/kg/day oral administration, both compounds (4 and 5) significantly decreased the serum cholesterol and triglyceride levels. Rat tissue lipid levels were reduced significantly by compound 4, while less effects resulted from compound 5. The cholesterol and triglyceride levels in chylomicrons, VLDL, and LDL fractions were reduced by both analogs while the HDL cholesterol levels were significantly increased. Compound 5 was also effective in lowering serum cholesterol and triglyceride levels in hyperlipidemic mice, at 8 mg/kg/day intraperitoneally, but not effective in hyperlipidemic rats at 8 mg/kg/day orally. Cholesterol and triglyceride lowering effects of the agents were correlated with inhibition of the activities of liver acetyl CoA synthetase, HMG CoA reductase, phosphatidylate phosphohydrolase, and lipoprotein lipase, and with elevation of the activity of cholesterol ester hydrolase.
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PMID:Hypolipidemic activity of 3-amino-1-(2,3,4-mononitro-, mono-, or dihalophenyl)propan-1-ones in rodents. 876 82

This paper provides a broad overview of biochemical risk factors such cholesterol and triglyceride in atherosclerotic cardiovascular diseases from the perspective of clinical laboratory medicine, since additional knowledge is needed in the genetic, biochemical, clinical and epidemiological spheres. Lipids play an important role in cell metabolism. Fatty acids and triglycerides, their storage form, are a high energy metabolic fuel. Cholesterol and phospholipids are essential components of cell membranes and cholesterol is a precursor of steroids. Cholesterol is delivered to the liver either from the intestine following dietary intake or is transported from extrahepatic tissues. It is removed from the liver through incorporation into lipoproteins by conversion into bile acids, and by secretion into bile. Lipoproteins are transported between tissues and organs in the form of particles. Lipoproteins are metabolically inert and apolipoproteins involve enzyme activation and inhibition of lipoprotein lipase, hepatic triglyceride lipase and lecithin-cholesterol acyltransferase. There is an exchange of components between lipoprotein particles facilitated by the cholesterol ester transfer protein. Lipoprotein receptors control the rate of cellular uptake and degradation and indirectly the rate of de novo cholesterol synthesis and individual subclasses of major lipoprotein species as well as the apolipoproteins and even the products of oxidative damage inflicted on the lipoprotein. This paper summarizes the relevant physiological and clinical knowledge and reviews a series of very practical data that must be understood to accurately quantify laboratory parameters.
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PMID:[Biochemistry of risk factors for cardiovascular diseases in laboratory medicine]. 895 35

Macrophages are a significant source of lipoprotein lipase (LPL) and apolipoprotein E (apo E) in the developing arterial wall lesion, and each of these proteins can importantly modulate lipid and lipoprotein metabolism by arterial wall cells. LPL and apo E share a number of cell surface binding sites, including proteoglycans, and we have previously shown that proteoglycans are important for modulating net secretion of apoprotein E from macrophages. We therefore evaluated a potential role for LPL in modulating net secretion of macrophage-derived apo E. In pulse-chase experiments, addition of LPL during the chase period produced a decrease in secretion of apoprotein E from human monocyte-derived macrophages, from the human monocytic THP1 cell line, and from J774 cells transfected to constitutively express a human apo E cDNA. LPL similarly reduced apo E secretion when it was prebound to the macrophage cell surface at 4 degrees C. A native LPL particle was required to modulate apo E secretion; addition of monomers and aggregates did not produce the same effect. Depletion of cell surface proteoglycans by a 72-h incubation in 4-methylumbelliferyl-beta-D-xyloside did not attenuate the ability of LPL to reduce apo E secretion. However, addition of receptor-associated protein attenuated the effect of LPL on apo E secretion. Although LPL could mediate removal of exogenously added apo E from the culture medium, detailed pulse-chase analysis suggested that it primarily prevented release of newly synthesized apo E from the cell layer. Cholesterol loading of cells or antibodies to the low density lipoprotein receptor attenuated LPL effects on apo E secretion. We postulate that LPL sequesters endogenously synthesized apo E at the cell surface by a low density lipoprotein receptor-dependent mechanism. Such post-translational regulation of macrophage apo E secretion by LPL could significantly influence apo E accumulation in arterial vessel wall lesions.
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PMID:Lipoprotein lipase reduces secretion of apolipoprotein E from macrophages. 914 8

The synthesis of cholesterol and its uptake from plasma LDL are regulated by two membrane-bound transcription factors, designated sterol regulatory element binding protein-1 and -2 (SREBP-1 and SREBP-2). Here, we used the technique of homologous recombination to generate mice with disruptions in the gene encoding the two isoforms of SREBP-1, termed SREBP-1a and SREBP-1c. Heterozygous gene-disrupted mice were phenotypically normal, but 50- 85% of the homozygous (-/-) mice died in utero at embryonic day 11. The surviving -/- mice appeared normal at birth and throughout life. Their livers expressed no functional SREBP-1. There was a 1.5-fold upregulation of SREBP-2 at the level of mRNA and a two- to threefold increase in the amount of mature SREBP-2 in liver nuclei. Previous studies showed that SREBP-2 is much more potent than SREBP-1c, the predominant hepatic isoform of SREBP-1, in activating transcription of genes encoding enzymes of cholesterol synthesis. Consistent with this observation, the SREBP-1 -/- animals manifested elevated levels of mRNAs for 3-hydroxy-3-methylglutaryl coenzyme A synthase and reductase, farnesyl diphosphate synthase, and squalene synthase. Cholesterol synthesis, as measured by the incorporation of [3H]water, was elevated threefold in livers of the -/- mice, and hepatic cholesterol content was increased by 50%. Fatty acid synthesis was decreased in livers of the -/- mice. The amount of white adipose tissue was not significantly decreased, and the levels of mRNAs for lipogenic enzymes, adipocyte lipid binding protein, lipoprotein lipase, and leptin were normal in the -/- mice. We conclude from these studies that SREBP-2 can replace SREBP-1 in regulating cholesterol synthesis in livers of mice and that the higher potency of SREBP-2 relative to SREBP-1c leads to excessive hepatic cholesterol synthesis in these animals.
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PMID:Elevated levels of SREBP-2 and cholesterol synthesis in livers of mice homozygous for a targeted disruption of the SREBP-1 gene. 937 3

High serum levels of total and LDL cholesterol are important risk factors in the development of atherosclerotic coronary artery disease. Cholesterol metabolism is affected by nutritional, environmental and genetic factors. Neuropeptide Y (NPY), which is widely expressed in both the central and peripheral nervous systems, has an important role in the hypothalamic regulation of energy balance by stimulating food intake and favoring energy storage through increased lipoprotein lipase activity in white adipose tissue. As a part of ongoing study of the genetic basis of obesity, we screened the NPY gene for sequence variants. We report here the identification of a common Leu(7)-to-Pro(7) polymorphism in the signal peptide of NPY. Presence of this Pro(7) in NPY was associated with higher serum levels of total and LDL cholesterol in obese subjects participating in two independent Finnish and Dutch studies. Furthermore, normal-weight Finns with Pro(7) also had higher serum levels of total and LDL cholesterol than did subjects with Leu(7)/Leu(7), as analyzed in three subsequent determinations at 5-year intervals during a 10-year follow-up period. The NPY polymorphism was not associated with higher cholesterol levels in normal-weight Dutch. Our study provides evidence that NPY is linked to cholesterol metabolism and that the polymorphism producing Pro(7) in NPY is one of the strongest genetic factors identified thus far affecting serum cholesterol, particularly in obese subjects.
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PMID:Association of a leucine(7)-to-proline(7) polymorphism in the signal peptide of neuropeptide Y with high serum cholesterol and LDL cholesterol levels. 984 84


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