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)

Diacylglycerol lipase activity has been demonstrated in human fetal membranes and decidua vera tissues. The specific activity of the enzyme is highest in the microsomal fraction of decidua vera tissue. The acylester bond at the sn-1 position of 1,2-diacyl-sn-glycerol is hydrolyzed followed by release of the fatty acid at the sn-2 position. The diacylglycerol lipase activity present in the microsomal fraction of decidua vera tissue hydrolyzes preferentially a diacylglycerol containing an arachidonoyl group in the sn-2 position. Monoacylglycerol lipase activity was also demonstrated in these tissues. The specific activity of monoacylglycerol lipase was significantly greater than that of diacylglycerol lipase and catalyzed preferentially the hydrolysis of monoacylglycerols containing an arachidonyl group in the sn-2 position. Based on the subcellular distribution and the differential effects of various inhibitors, we suggest that the monoacylglycerol lipase and diacylglycerol lipase in decidua vera tissue are 2 distinct enzymes. Diacylglycerol kinase specific activity was examined also and was found to be 4-5 times greater in amnion than in either chorion laeve or decidua vera. The importance of diacylglycerol metabolism in the mechanism of arachidonic acid release and prostaglandin biosynthesis is discussed.
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PMID:Diacylglycerol metabolism and arachidonic acid release in human fetal membranes and decidua vera. 678 66

Rat Brain has a lipase which hydrolyzes diacylglycerol at an optimal pH of 4.8 (1). The subcellular distribution of this acid diacylglycerol lipase was studied in brain tissue of rats and mice; in the latter case neurological mutants and their normal controls were used. Several other acidic hydrolases were employed as normal controls were used. Several other acidic hydrolases were employed as lysosomal markers. In mouse brain, the specific activity which is about 50-100 times lower than in rat brain, was greatest in the lysosomal fraction. In contrast, no enrichment of DG-lipase was observed in any subcellular fraction of the active enzyme of rat brain. Activities were about equally distributed in the microsomal, myelin-synaptosomal and lysosomal fractions.
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PMID:Subcellular distribution of diacylglycerol lipase in rat and mouse brain. 688 45

Previous studies with healthy volunteers and non-insulin-dependent diabetic (NIDDM) patients have shown a strong association between overall glucose metabolism and hepatic microsomal enzyme activity. In this study, the effects of 10-day oral administration of phenobarbital (PB), a potent inducer of the hepatic microsomal mixed-function oxidase system, on carbohydrate and lipid metabolism in the basal state and on glucose kinetics during submaximal hyperinsulinemic (5 mU.kg-1.min-1 insulin) clamps were investigated in nondiabetic rats and in rats made diabetic by the intravenous (IV) administration of either low-dose (40 mg/kg) or high-dose (55 mg/kg) streptozocin (STZ). In control rats receiving PB in drinking water (0.5 mg/mL), serum insulin and triglyceride levels were diminished without any change in glucose and cholesterol concentrations in the fed state. Administration of PB in drinking water (0.25 mg/mL) to both groups of diabetic rats decreased their water intake and serum triglyceride levels in the absence of an effect on glucose, insulin, and cholesterol concentrations in the fed state. However, fasting serum glucose levels and basal glucose turnover rates were lower in both groups of diabetic rats receiving PB. PB treatment increased the heparin-releasable lipoprotein lipase (LPL) activity of epididymal fat in both control and low-dose diabetic groups; this was not assessed in the high-dose diabetic group. Neither peripheral glucose utilization nor hepatic glucose production during submaximal insulin clamps was modified by PB treatment in nondiabetic rats. In contrast, PB administration enhanced insulin-mediated peripheral glucose utilization, as well as suppression of hepatic glucose production, in both low-dose and high-dose diabetic groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phenobarbital treatment enhances insulin-mediated glucose metabolism and improves lipid metabolism in the diabetic rat. 813 83

1. The effect of magnesium and dl-propranolol on phosphatidate phosphohydrolase (PAPase) and diacylglycerol lipase (DGL) activities in isolated rod outer segments (ROS) and of the former on subcellular fractions from bovine retina was investigated. 2. Mg(2+)-independent PAPase activity was found in ROS, whereas in the other subcellular fractions PAPase activities both dependent on and independent of Mg2+ were detected. 3. The membrane-bound PAPase activity was stimulated at low concentrations of Mg2+ and inhibited at higher concentrations. The soluble activity was always stimulated by the ion. 4. dl-Propranolol (1000 microM) exerted a slight stimulatory effect on PAPase in ROS whereas total PAPase activity of microsomal fraction was not affected. 5. Mg2+ (0.2 mM) stimulated DGL activity (30%) whereas it was inhibited at higher concentration. 6. DGL lipase activities, both dependent on and independent of Mg2+, were detected in subcellular fractions of bovine retina. 7. DGL properties in ROS are also described.
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PMID:Differential properties of phosphatidate phosphohydrolase and diacylglyceride lipase activities in retinal subcellular fractions and rod outer segments. 844 87

The effectiveness of plasma lipid lowering in the clinic is well supported by a growing number of contributions, indicating the significant improvement in cardiovascular risk in primary and particularly in secondary prevention. While these studies have clearly indicated that the more potent agents for cholesterol reduction can provide a very effective help, other pathways of lipid metabolism have gained interest. These should be evaluated, in the hope of providing a more complete answer to the question of regulating lipid absorption, distribution, and tissue deposition. In addition to newer more potent systemic lipid-lowering drugs (in particular hydroxymethylglutaryl coenzyme A reductase inhibitors), nonsystemic agents, including cholesterol sequestrants, are receiving attention. Some of these are effective at low concentrations, thus providing a potentially powerful tool for plasma cholesterol regulation. Another area of development is that of acyl coenzyme A cholesterol acyltransferase inhibitors, i.e., drugs interfering with cholesterol esterification in tissues, particularly in the arterial wall; the major problem with these seems to be that of poor tolerability and of lack of definitive proof of plasma cholesterol reduction in humans. At present, drugs for the treatment of elevated lipoprotein(a) levels are not available, with few exceptions; in this case, a better understanding of the regulation of lipoprotein(a) metabolism and of the potential benefit of treatment seems necessary. Elevation of congenitally low high density lipoprotein cholesterol levels may also be an important target: microsomal enzyme inducers have been tested, but have not provided a clinically significant response; drugs with a mixed endocrine-hypolipidemic activity possibly may prove effective. Other targets, e.g., the correction of the lipoprotein pattern characterized by "small low density lipoprotein," and the development of drugs specifically acting on the cholesteryl ester transfer protein and lipoprotein lipase systems, are being explored. Finally, new areas of development are in recombinant apolipoproteins (apo's) and in gene therapy. One case, i.e., that of apo A-I/HDL, is entering the clinical field; the mutant apo A-IMilano might provide help because of a combined cholesterol removing/fibrinolytic activity. In the case of gene therapy, at present, data on low density lipoprotein receptor replacement are encouraging. Further options, such as gene transfer in the arterial wall to induce vascular protection/disobliteration of occlusions, are also being tested.
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PMID:New targets for lipid lowering and atherosclerosis prevention. 857 25

The effect of atorvastatin (3 mg kg(-1) day(-1)), simvastatin (3 mg kg(-1) day(-1)) and bezafibrate (100 mg kg(-1) day(-1)) administered for 4 weeks to male New Zealand white rabbits on enzyme activities related to lipid metabolism has been studied. Only the statins reduced plasma cholesterol values, while none of the drugs modified plasma triglyceride or high density lipoprotein (HDL)-cholesterol concentrations, nor the activity of enzymes such as hepatic diacylglycerol acyltransferase, lipoprotein lipase or hepatic lipase, directly involved in triglyceride metabolism. Both statins elicited similar increases in the hepatic microsomal 3-hydroxy-3-methyl-glutaryl Coenzyme A (CoA) reductase activity (147 and 109% induction for simvastatin and atorvastatin, respectively), and none of the drugs assayed modified hepatic acyl-coenzyme A:cholesterol acyltransferase activity significantly. Only bezafibrate induced a significant 57% reduction in the activity of hepatic microsomal cholesterol 7alpha-hydroxylase. Regarding the rate limiting enzyme of phosphatidylcholine biosynthesis, CTP:phosphocholine cytidylyl transferase, atorvastatin and bezafibrate behaved similarly, decreasing the enzyme activity in the liver by 45% and 54%, respectively; simvastatin induced no modification of this activity. The reduction of CTP:phosphocholine cytidylyl transferase activity is not caused by a direct inhibition of the enzyme by bezafibrate and atorvastatin. Further, the inhibitory effect of atorvastatin appears to be unrelated to the inhibition of 3-hydroxy-3-methyl-glutaryl CoA reductase elicited in vivo.
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PMID:Effect of hypolipidemic drugs on key enzyme activities related to lipid metabolism in normolipidemic rabbits. 965 95

Familial combined hyperlipidaemia (FCH) is not a single entity with a clearly defined cause but can occur through an increased fatty acid flux from adipose cells, lipoprotein lipase dysfunction or apolipoprotein CIII abnormalities. A dynamic model of the metabolic processes of FCH has been used to describe how lipolysis of adipose cells may ultimately contribute to the formation of atherosclerotic plaques. Elevated circulating levels of chylomicrons are broken down to produce atherogenic remnants. One of the roles of lipoprotein lipase is in the low density lipoprotein (LDL) receptor-like protein-mediated uptake of lipoprotein remnants in the liver and up to 20% of FCH patients show a genetic abnormality of this enzyme. Vitamin A loading and measurement of chylomicron retinyl palmitate levels has further demonstrated impaired chylomicron remnant metabolism in these patients. Macrophages located in the vascular walls engulf remnants but are unable to metabolize their cholesterol. These cells contribute to atherosclerotic plaques. In terms of atherogenic potential, triglyceride levels are found to be higher and the hypertriglyceridaemia more severe in fed than in fasted patients. A case study of a patient with abetalipoproteinaemia suggests that the hypertriglyceridaemia seen in patients with FCH may be the result of an abnormality in microsomal triglyceride transport protein function. Studies also suggest a direct relationship between the post-prandial triglyceride levels and LDL cholesterol levels in the fasting state of patients with FCH and sporadic hypercholesterolaemia.
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PMID:Metabolic basis for hypertriglyceridaemia in familial combined hyperlipidaemia. 971 61

There is accumulating evidence for the importance of small, dense low-density lipoprotein (LDL), the defining feature of the atherogenic lipoprotein phenotype, as a risk factor for coronary heart disease. Although both family studies and twin studies have demonstrated genetic influences on this phenotype, the specific gene(s) involved remain to be identified. The purpose of this study was to determine whether there was evidence for genetic linkage between small, dense LDL (LDL subclass phenotype B), as determined by gradient gel electrophoresis, and selected candidate genes known to be involved in lipid metabolism. The linkage analyses were based on a sample of 19 families, including 142 individual family members, using a lod score linkage analysis approach. Nine candidate genes were examined, including loci for manganese superoxide dismutase (Mn SOD2), apolipoproteins CIII, AII, and apo CII, lipoprotein lipase, hepatic lipase, microsomal triglyceride transport protein, the insulin receptor and the LDL receptor. The analyses did not provide significant evidence for genetic linkage between markers for any of these genes and LDL subclass phenotype B, nor did it confirm previous reports of linkage between the LDL receptor gene and LDL subclass phenotype B. Using three closely linked markers for the Mn SOD2 locus excluded close linkage between this candidate gene region and LDL subclass phenotype B. These findings demonstrate the complexity of genetically mapping risk factor phenotypes, and emphasize the necessity of identifying new genetic loci, other than known candidate genes, involved in susceptibility to atherosclerosis.
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PMID:Linkage analysis of candidate genes and the small, dense low-density lipoprotein phenotype. 992 May 8

This study investigated the potential alteration in the amount of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase messenger RNA (mRNA) and lipoprotein lipase (LPL) mRNA in the livers of C57BL/6 mice after long-term (200 days) treatment with the nonionic surfactant called poloxamer 407 (P-407). Previously, P-407 has been used to produce a dose-controlled hyperlipidemic state in C57BL/6 mice with subsequent formation of atherosclerotic lesions. Five groups of mice were studied; controls (C); mice fed a standard chow diet enriched with only cholic acid (CH); mice fed the high-cholesterol, high-fat Paigen diet (HF); mice treated with 0.5 g/kg P-407 every third day (P); and mice administered 0.5 g/kg P-407 every third day while consuming a diet identical to that of mice in group CH (PC). Neither a significant (p < 0.05) weight loss nor alteration in liver enzymes (AST and ALT) were observed for any group throughout the study when compared with the control mice. Total plasma cholesterol (CHOL) was significantly elevated compared with controls for mice in groups HF, P, and PC, whereas total plasma triglycerides (TG) were significantly increased for mice in only groups P and PC. Long-term ingestion of a high-fat diet or a diet enriched in cholic acid resulted in a significant (p < 0.05) reduction in HDL-CHOL when compared with controls. Plasma samples assayed at 200 days for mice in groups HF and P showed a shift in the lipoprotein fraction distribution primarily to VLDL-CHOL as compared with mice in group C in which, as expected, most of the CHOL was contained in the HDL fraction. The biologic activity of HMG-CoA reductase assayed in hepatic microsomal homogenates was significantly reduced for mice in groups CH (p < 0.01), HF (p < 0.01), and PC (p < 0.05), but not for mice in group P, when compared with control. A statistical analysis of the data demonstrated significant (p < 0.05) reductions in the HMG-CoA reductase mRNA levels in hepatic tissue for all treatment groups relative to mRNA levels determined for mice in group C. In contrast, no treatment group demonstrated a significant difference in hepatic LPL mRNA levels when compared with mRNA levels determined for control animals. These data demonstrate that P-407 administration to C57BL/6 mice significantly decreased the amount of HMG-CoA reductase mRNA detected in liver.
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PMID:Potential downregulation of HMG-CoA reductase after prolonged administration of P-407 in C57BL/6 mice. 1059 27

While human diets have markedly evolved since their origin, the human genome has only marginally changed. Nevertheless, polymorphisms of common genes are widespread. It has been substantiated that most major diseases (including cardiovascular disease, diabetes, obesity and cancers) result from the interaction between genetic susceptibility and environmental factors, including diet. In the field of lipoprotein metabolism and cardiovascular disease several gene polymorphisms for key proteins, such as apoproteins (apo) E, B, A-IV and C-III, LDL receptor, microsomal transfer protein (MTP), fatty acid-binding protein (FABP), cholesteryl ester transfer protein (CETP), lipoprotein lipase and hepatic lipase, have been identified and linked to variable responses to diets. We are carrying out an intervention study (RIVAGE) in Marseille dedicated to investigating the interactions between diets (Mediterranean or low-fat types v. standard Western type), risk factors for cardiovascular disease and gene polymorphisms in about 300 patients randomized into two groups over periods of 3 and 12 months. Some data obtained in about 100 patients after 3 months of dietary change are available. Among single nucleotide polymorphisms (SNP) already studied (apoE (epsilon2, epsilon3, epsilon4), apoB (-516C/T), apoC-III (SstI), apoA-IV (Ser347Thr), MTP (-493G/T), intestinal FABP (Ala54Thr), CETP (TaqIB) and hepatic lipase (-480C/T)), some SNP showed interactions with diets in relation to changes in particular variables after 3 months on the dietary regimens. This was the case for apoE and LDL-cholesterol and triacylglycerols, apoA-IV and LDL-cholesterol, MTP and LDL-cholesterol, intestinal FABP and triacylglycerols. These data provide evidence of the interaction between some SNP and the metabolic response to diets.
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PMID:Genetic polymorphisms and lipoprotein responses to diets. 1269 Nov 71


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