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)

In order to determine the role of apoprotein (apo) B conformation in the activation of the lysolecithin acyl-transferase reaction, we studied the activation of purified enzyme by various subfractions of low density lipoprotein (LDL), isolated by density gradient centrifugation. The activation of LAT correlated positively with the density of LDL and negatively with cholesterol/protein and triglyceride (TG)/protein ratios. The enzyme activation was also positively correlated with the number of trinitrobenzenesulfonic acid-reactive lysine amino groups, which increased with increasing density of LDL. The immunoaffinity of the LDL subfractions for B1B6, a monoclonal antibody directed to the receptor-binding region of apoB, increased with increasing density, while the affinity toward C1.4, a monoclonal antibody directed to the amino-terminal region of apoB, was not altered. Enrichment of normal whole LDL with TG resulted in a 45% reduction in enzyme activation, a 27% decrease in the number of trinitrobenzenesulfonic acid-reactive lysine groups, and a marked reduction in the immunoaffinity for B1B6. All these parameters reversed to normal when the TG-enriched LDL was treated with milk lipoprotein lipase, which specifically reduced the TG content of LDL. The LDL subfractions also supported cholesterol esterification by the purified enzyme, in parallel with lysolecithin esterification, indicating that apoB can also serve as an activator of the lecithin-cholesterol acyltransferase reaction. These results strongly suggest that the localized conformational change of apoB which occurs during the TG depletion of the precursor particle is critical for its activation of acyltransferase reactions, in a manner analogous to its interaction with the cellular receptors.
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PMID:Effect of apoprotein B conformation on the activation of lysolecithin acyltransferase and lecithin: cholesterol acyltransferase. Studies with subfractions of low density lipoproteins. 154 96

A comprehensive assessment of lipoprotein compositional/metabolic response to incremental caloric ethanol (EtOH) doses ranging from low to moderate to high was undertaken using male squirrel monkeys. Control monkeys were maintained on a chemically defined, isocaloric liquid diet, while experimental primates wee fed increasing doses of alcohol (6, 12, 18, 24, 30, and 36% of energy) substituted isocalorically for carbohydrate at 3-month intervals. Liver function tests and plasma triglyceride were normal for all animals. Plasma cholesterol showed a transient increase at the 12% caloric dose that was attributed solely to an increase in high density lipoprotein (HDL). A more pronounced increase in plasma sterol, beginning at 24% and continuing to 36% EtOH, was the result of increments in both HDL and low density lipoprotein (LDL) cholesterol, although the contribution by the latter was substantial primarily at the 36% dose. Plasma apolipoprotein elevations (HDL apolipoprotein A-I, LDL apolipoprotein B) generally accompanied the lipoprotein lipid increases, although the first atherogenic response for LDL became manifest as a significant increase in apolipoprotein B at 18% EtOH calories. Postheparin plasma lipoprotein lipase was not affected by dietary alcohol, whereas hepatic triglyceride lipase activity showed significant increases at higher (24 and 36%) EtOH doses. Plasma lecithin-cholesterol acyltransferase activity was normal at the 6 and 12% EtOH doses, but exhibited a significant reduction beginning at 18% and continuing to 36% EtOH. Alterations in these key lipoprotein regulatory enzymes may represent the underlying metabolic basis for the observed changes in lipoprotein levels and our earlier findings of HDL2/HDL3 subfraction modifications. Results from our study indicate that in squirrel monkeys, moderate (12%) EtOH caloric intake favors an antiatherogenic lipoprotein profile (increases HDL, normal LDL levels, and lecithin-cholesterol acyltransferase activity), whereas higher doses (24-36%) produce both coronary-protective (increases HDL) and atherogenic (increases LDL) responses. Moreover, the 18% EtOH level represents an important transition dose which signals early adverse alterations in lipoprotein composition (increases apolipoprotein B) and metabolism (decreases lecithin-cholesterol acyltransferase).
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PMID:Alcohol produces dose-dependent antiatherogenic and atherogenic plasma lipoprotein responses. 157 Mar 59

With a view toward elucidating the poorly understood high density lipoprotein (HDL) metabolism in familial hypercholesterolemic (FH) patients, the activities of the plasma enzymes involved in HDL metabolism; hepatic triglyceride lipase (HTGL), lipoprotein lipase (LPL) and lecithin-cholesterol acyltransferase (LCAT) with concomitant determination of HDL particle size, were analyzed in 50 age-matched hypercholesterolemic patients (26 FH and 24 non-FH patients). The activity of HTGL in FH patients was significantly higher (p less than 0.02) than in non-FH patients. The analysis of HDL size by gradient gel electrophoresis showed significantly smaller HDL particles in FH patients. Analysis of the correlation between HTGL activity and HDL particle size confirmed that the variation in HDL particle size was related to HTGL activity. Those results suggest that the differences in HTGL activity and HDL size between the familial and non-familial types of hypercholesterolemia may be due to differences in their pathophysiology. The high HTGL activity and small HDL particles in FH probably are the consequences of an adaptational mechanism used by LDL-receptor-deficient hepatocytes to increase the intracellular pool of cholesterol.
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PMID:Hepatic lipase activity and high density lipoproteins in familial hypercholesterolemia: adaptational mechanisms for LDL-receptor deficient state. 196 95

Rats administered estrogen-progestin formulation (0.667 mg of synthetic progestin and 0.067 mg of synthetic estrogen/kg body wt) showed increased hepatic cholesterogenesis, as evidenced by an increased activity of HMG-CoA reductase and increased incorporation of labelled acetate into liver cholesterol. Hepatic degradation of cholesterol to bile acids, however, was decreased. There was increased release of lipoproteins into the circulation but their clearance from the circulation was lower as revealed by a decreased activity of lipoprotein lipase of the extrahepatic tissues. Activity of plasma LCAT, which is involved in the transport of cholesterol from the tissues, was also decreased. The increase in serum and aortic cholesterol levels, increase in LDL cholesterol and decrease in HDL cholesterol in rats administered estrogen-progestin formulation suggest that prolonged administration of this formulation may predispose towards atherosclerosis.
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PMID:Mechanism of hyperlipidemia produced by estrogen-progestin formulation. 207 Nov 84

There is little doubt today that apolipoproteins play a key role in lipid metabolism and thus in atherogenesis. There are five major classes of apo Lp known: Apo AI, the main component of HDL not only mediates the action of LCAT, a key enzyme in cholesterol metabolism, but also through specific cell receptors is responsible for the reverse cholesterol transport, which is discussed as the main atherogenic process. Apo B is necessary for the secretion of neutral lipids out of the liver and the intestine. In addition, apo B containing lipoproteins are recognized by specific cell surface receptors leading to the fast removal of cholesterol rich fractions from circulation. Apo C proteins regulate the activity of lipoprotein lipase, the key enzyme of triglyceride metabolism. Apo E containing lipoproteins are recognized by the B/E-receptor with a 10 to 100 fold affinity. There exists, however, another specific receptor for Apo E, which is responsible for the fast removal of the atherogenic remnants from circulation. Apo E in addition serves to secrete deposited cholesterol out of macrophages and foam cells. Apolipoprotein(a) is a peculiar fraction of apo B containing lipoproteins whose biological function is completely unknown. Cloning of the cDNA revealed striking similarities of apo(a) with the structure of plasminogen. The cross connection of Lp(a) with hemostasis and thrombogenesis is currently focus of intensive research. The knowledge of the specific function of apolipoproteins in lipid metabolism arose to a great extent from the characterization of apo-Lp isoforms and their impact of atherogenesis. In addition, intensive research by molecular biology techniques helped to unravel the pathophysiology in a wide array.
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PMID:[The role of apolipoproteins in lipid metabolism]. 216 81

CAD results from atherosclerosis, a chronic disease process that has its origin in childhood. Children and adolescents can be at higher risk for CAD by virtue of being from families with premature CAD or familial dyslipoproteinemias. The plasma lipid and lipoprotein levels result from a number of complex metabolic processes that are under the control of genetic and environmental (e.g., diet) influences. The normal ranges of plasma lipids and lipoproteins in children are known, and children and adolescents with dyslipoproteinemia are ordinarily defined as those having levels of plasma total, LDL, or triglyceride above the 95th percentile or with a low HDL cholesterol below the 5th percentile. Children of a parent with documented dyslipoproteinemia or with family history of premature CAD may be screened in the fasting state any time after 2 years of age. Following the exclusion of secondary causes of dyslipoproteinemia, the diagnosis of primary dyslipoproteinemia can be made. Lipoprotein patterns are not diagnostic for a given genotype. Efforts to determine further the biochemical defects responsible for a given phenotype have led to the investigation of gene coding for the apolipoproteins, the key enzymes in the lipoproteins pathways (LPL, HDL, and LCAT) and the receptors that process lipoproteins, such as the LDL receptor and the chylomicron remnant receptor. From a practical standpoint, the diagnosis of the kind of dyslipoproteinemia in a child will depend upon the nature and severity of the dyslipoproteinemia, both in the child (or adolescent) and in parents and siblings. Marked increases in plasma total and LDL cholesterol in the child and in at least one of the parents often reflect the presence of familial hypercholesterolemia, an inherited dominant condition due to a defect in the LDL receptor gene. The triglyceride levels are often normal. If the child has a different dyslipoproteinemia pattern from siblings and parents, then the diagnosis of familial combined hyperlipidemia or hyperapobetalipoproteinemia should be considered. Most children with mild or borderline elevations in total and LDL cholesterol will have polygenic hypercholesterolemia. Triglyceride problems in children and adolescents are relatively uncommon, particularly the more severe hypertriglyceridemia such as that found in lipoprotein lipase and apoC-II deficiency, dysbetalipoproteinemia, and type V hyperlipoproteinemia. High levels of Lp(a) lipoprotein, in isolation or in combination with other dyslipoproteinemia, accelerate risk for CAD. Low levels of HDL cholesterol in the absence of other abnormalities suggest the diagnosis of hypoalphalipoproteinemia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Diagnosis and management of familial dyslipoproteinemia in children and adolescents. 225 50

(1) Human HDL2 (d 1.070-1.125) and HDL3 (d 1.125-1.21) labelled with unesterified [14C]cholesterol, were incubated with a source of lecithin-cholesterol acyltransferase. For optimal activity, the reaction required the addition of albumin in excess, at least 3-times greater than the concentration of HDL-free cholesterol. Under such conditions, the reaction appeared saturable. HDL3 was found the most efficient substrate and the Vmax values expressed for 1.5 IU LCAT/ml and with an albumin/free cholesterol ratio of 3, were 8.3 nmol free cholesterol esterified/ml per h and 4.1 nmol/ml per h for HDL3 and HDL2, respectively. (2) HDL3 were modified in the presence of VLDL by inducing triacylglycerol lipolysis with a semipurified lipoprotein lipase from bovine milk. The newly formed HDL had gained free cholesterol and phospholipids, so that about 50% of these modified HDL, referred to as light-LIP-HDL3, were reisolated in the HDL2 density range. Light-LIP-HDL3 were enriched mostly in free cholesterol (+ 160%) and in phospholipid (+ 40%). Their reactivity towards LCAT was half-reduced compared to parent HDL3, which correlated well with a decrease in their phospholipid/free cholesterol molar ratio. Moreover, HDL3 artificially enriched in free cholesterol and exhibiting a comparable PL/FC behaved like lipolysis-modified HDL in their reactivity towards LCAT. (3) HDL3 were also modified by co-incubation with VLDL (post-VLDL-HDL3), or with VLDL and a source of lipid transfer protein (CET-HDL3). The latter treatment greatly affected the lipid composition of the core particle (-25% esterified cholesterol, +190% TG). In both cases, the moderate decreasing LCAT reactivity observed could be related to the phospholipid/free cholesterol ratio. Thus, like in artificial substrates, the lipid composition of the HDL surface may control the rate of LCAT-mediated cholesterol esterification.
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PMID:Reactivity of HDL subfractions towards lecithin-cholesterol acyltransferase. Modulation by their content in free cholesterol. 280 54

(1) Human HDL2 (d 1.063-1.125) and HDL3 (d 1.125-1.210), labelled with 2-[14C]oleoylphosphatidylcholine (PC), and with/without tri[3H]oleoylglycerol, were incubated with a partially purified human hepatic triacylglycerol lipase, at pH 8.5. PC hydrolysis was linear up to 90-120 min incubation and within a range of lipase activities, from 50 to 500 mIU/ml. At low degrees of lipolysis, the hydrolysis of triacylglycerol was linearly related to that of PC, but the relative degradation rate was 10-fold higher for the former, which was thus very rapidly consumed. HDL subfractions were then differentiated in terms of PC hydrolysis. Km values were 0.32 and 0.43 mM for HDL2 PC and HDL3 PC, respectively. The corresponding Vmax values expressed for 200 mIU/ml hepatic lipase activity were 41.0 nmol PC hydrolysed/ml per h (HDL2) and 28.6 nmol PC/ml per h (HDL3). (2) HDL3 were modified in the presence of VLDL by inducing triacylglycerol lipolysis in VLDL with a semi-purified human plasma or bovine milk lipoprotein lipase (LPL). Lipolysis-modified HDL3 (LIP-HDL3) were mostly enriched in free cholesterol (+80%, P less than 0.05) and to a lesser extent in triacylglycerol (+33%). As a consequence, 45% of the LIP-HDL3 was reisolated in the HDL2-density interval, and is referred to as light LIP-HDL3. LIP-HDL3 displayed a 65% increase in its reactivity towards hepatic lipase compared to control HDL3. The light LIP-HDL3 showed the lowest Km (0.19 mM PC) and the highest Vmax (69 nmol/ml per h) of all HDL tested. Coincubation of HDL3 with VLDL and albumin did not alter the further reactivity of HDL3 towards hepatic lipase. Cholesterol loading of HDL3 by celite-cholesterol dispersions also led to an enhanced reactivity, though less important than with the lipolysis modification. (3) HDL3 were also modified by coincubation with VLDL and the lecithin-cholesterol acyltransferase-inhibited plasma fraction of d greater than 1.21 g/ml, thus allowing the cholesteryl ester transfer reaction to occur. The modified HDL3 (CET-HDL3) were depleted in esterified cholesterol (-25%, P less than 0.05) and enriched in triacylglycerol (+70%, P less than 0.05). However, these particles behaved like control HDL3 in their reactivity towards hepatic triacylglycerol lipase. Thus, the hydrolysis of HDL PC mediated by hepatic triacylglycerol lipase appears to be influenced by changes occurring in the particle's surface rather than in the lipid core.
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PMID:Phosphatidylcholine and triacylglycerol hydrolysis in HDL as induced by hepatic lipase: modulation of the phospholipase activity by changes in the particle surface or in the lipid core. 291 47

A structural homology between lipoprotein lipase, pancreatic lipase and hepatic lipase is known and indicates that all three lipases are members of a common protein family. Lipoprotein lipase and pancreatic lipase utilize small protein co-factors, apolipoprotein C-II and co-lipase, respectively, but comparisons reveal no homology between the co-factor molecules. Hence, they do not show the same relationship as their target enzymes. Neither do screenings detect any extensive similarities between lipoprotein lipase, serine hydrolases, or apolipoproteins. Scannings against data bank proteins show that a 105-residue segment of lipoprotein lipases exhibits a 35-40% residue identity with a sub-region of Drosophila vitellogenins. One fifth of the conserved amino acid residues (8 of 40) are glycine, a pattern which is typical of distantly related forms of protein families. This supports a true relationship between large segments of Drosophila vitellogenins and lipases. Physiological and functional aspects of the vitellogenin/lipoprotein lipase similarities are given. The region concerned is entirely within the N-terminal domain of lipoprotein lipase and constitutes the segment where the similarity to hepatic and pancreatic lipases is most pronounced. Within this lipase region a 10-residue putative lipid-binding site exists for which further similarities have been found to the otherwise not closely related lingual/gastric lipases, prokaryotic lipases and lecithin-cholesterol acyltransferase. Another segment in lipoprotein lipase, where the heparin-binding site has been mapped, exhibits a correlation between strength of heparin binding and extent of basic residues among members of the lipase family. It further exhibits weak similarities with the 'Zn-finger' DNA-binding segment of steroid hormone receptors and may indicate convergence in a binding interaction. Thus, a functional subdivision of lipoprotein lipase into different segments can be distinguished.
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PMID:Structural features of lipoprotein lipase. Lipase family relationships, binding interactions, non-equivalence of lipase cofactors, vitellogenin similarities and functional subdivision of lipoprotein lipase. 291 65

The effect of high dose medroxyprogesterone acetate (MPA) on serum lipids, on adipose tissue lipoprotein lipase (LPL) and serum lecithin cholesterol acyltransferase activities were studied in 15 postmenopausal patients with endometrial cancer. After 2 weeks of MPA treatment total cholesterol decreased by 14% (P less than 0.001) and HDL cholesterol by 33% (P less than 0.01) from the respective pretreatment values; correspondingly the ratio of HDL to total cholesterol decreased (P less than 0.05). The decrease of HDL2 cholesterol was 35% (P less than 0.01) and that of HDL3 cholesterol 15% (P less than 0.01). The levels of serum triglycerides decreased significantly (P less than 0.05) during the treatment period. Serum LCAT activity was significantly lower (P less than 0.05) after treatment than before, but adipose tissue LPL activity was not altered. The mean serum testosterone level decreased significantly (P less than 0.001) from the pretreatment values. Significant positive correlations were present between LPL activity and MPA concentrations and between LPL activity and testosterone concentrations after the drug treatment.
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PMID:Effects of high dose progestin on serum lipids and lipid metabolizing enzymes in patients with endometrial cancer. 315 2


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