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)

The acute effects of intravenous heparin administration (50 U/kg body weight) on apolipoprotein (apo)B-48 and apoB-100-containing lipoproteins in relation to postheparin lipase activities were studied in ten healthy normolipidemic volunteers. Five subjects returned to receive sham injections with saline. Lipoproteins were separated from plasma by density gradient ultracentrifugation at baseline, 3, and 20 min postheparin. ApoB-48 and apoB-100 in d < 1.006 g/mL and 1.006 < d < 1.019 g/mL fractions were quantitatively measured after electrophoresis on 5% SDS polyacrylamide gels and Coomassie-blue staining. No significant changes were observed after saline injections. Heparin administration released lipoprotein lipase (LPL) and hepatic lipase (HL) activities after 20 min, and significantly reduced apoB-48 concentrations in d < 1.006 g/mL fractions only. ApoB-100 concentrations showed a trend to decrease in d < 1.006 g/mL fractions and to increase in 1.006 < d < 1.019 g/mL fractions. LPL activity was related to the percentual disappearance of apoB-48 (r = 0.81, P = 0.004) and apoB-100 (r = 0.91, P < 0.001) in d < 1.006 g/mL fractions. When little LPL was released (LPL activity < 120 mU/mL) by heparin, apoB-48 was preferentially eliminated over apoB-100. However, when abundant LPL was released (LPL activity > 140 mU/mL), comparable percentual reductions for apoB-48 and apoB-100 were seen. Pharmacokinetic analysis revealed first-order kinetics for the clearance of apoB-48 in d < 1.006 g/mL fractions, but zero-order kinetics for apoB-100 clearance. Under conditions of artificially enhanced lipolysis, the first catabolic step of apoB-48-containing lipoproteins and hepatic VLDL showed different pharmacokinetics. ApoB-48-containing lipoproteins were the preferred substrate for LPL, and only when abundant LPL was present, clearance of hepatic VLDL occurred.
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PMID:Preferential clearance of apoB-48-containing lipoproteins after heparin-induced lipolysis is modulated by lipoprotein lipase activity. 950 93

A panel of 13 monoclonal antibodies to avian lipoprotein lipase (LPL) was screened for inhibition of LPL binding to primary avian adipocytes. One monoclonal antibody, designated xCAL (monoclonal antibody to chicken adipose lipoprotein lipase) 3-6a, was found to inhibit the binding of LPL to primary avian adipocytes. In solid phase assays, xCAL 3-6a inhibited the binding of LPL to both heparan sulfate and heparin. XCAL 3-6a did not inhibit the catalytic activity of the avian enzyme. The monoclonal antibody was not found to cross-react significantly with bovine lipoprotein lipase. In order to determine the location of the epitope of xCAL 3-6a on lipoprotein lipase, several avian lipoprotein lipase deletion mutants were constructed and produced as glutathione S-transferase (GST) fusion proteins in E. coli. These mutants were screened for their ability to react with xCAL 3-6a using Western blotting. The minimum continuous fragment of lipoprotein lipase that was required for reactivity contained the amino acids 310 to 450. Site-directed mutagenesis of basic residues 321, 405, 407, 409, 415, and 416 revealed that Arg 405 is necessary for the interaction of LPL with xCAL 3-6a. Additional deletions of either the amino- or carboxyl-terminal portion of the fragment containing residues 310-450 resulted in loss of antibody binding, suggesting that the epitope is a discontinuous one that is formed when the termini are brought together through protein folding. Heparin-Sepharose chromatography of wild-type LPL and a mutant LPL in which the well-characterized heparin-binding sequence (Arg 281-Lys 282-Arg 284) has been mutated was carried out in the presence and absence of xCAL 3-6a. These experiments indicate that lipoprotein lipase contains a heparin-binding domain, in addition to Arg 281-Arg 284, that can be blocked by xCAL 3-6a.
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PMID:Identification of the epitope of a monoclonal antibody that inhibits heparin binding of lipoprotein lipase: new evidence for a carboxyl-terminal heparin-binding domain. 954 95

The present study examined the influence of training, followed by a short period of detraining, on postprandial lipaemia. Fourteen normolipidaemic, recreationally active young adults aged 18-31 years participated, in two self-selected groups: three men and five women (BMI 21.7-27.6 kg/m2) completed 13 weeks of running training, after which they refrained from exercise for 9 d; three men and three women (BMI 21.5-25.6 kg/m2) maintained their usual lifestyle. Oral fat tolerance tests were conducted at baseline and again 15 h, 60 h and 9 d after the runners' last training session. Blood samples were drawn after an overnight fast and at intervals for 6 h after consumption of a high-fat meal (1.2 g fat, 1.4 g carbohydrate, 70.6 kJ energy/kg body mass). Heparin was then administered (100 IU/kg) and a further blood sample was drawn for measurement of plasma lipoprotein lipase (EC 3.1.1.34; LPL) activity. Endurance fitness improved in runners, relative to controls (maximal O2 uptake +3.2 (SE 1.1) ml/kg per min v. -1.3 (SE 1.2) ml/kg per min; P < 0.05). In the absence of the acute effect of exercise, i.e. 60 h after the last training session, there was no effect of training on either postprandial lipaemia or on post-heparin LPL activity. However, changes during 9 d of detraining in both these variables differed significantly between groups; after 2d without exercise (60 h test), the runners' lipaemic response was 37% higher than it was the morning after their last training session (15 h test; runners v. controls P < 0.05), with a reciprocal decrease in post-heparin LPL activity (P < 0.01). These findings suggest that improved fitness does not necessarily confer an effect on postprandial lipaemia above that attributable to a single session of exercise.
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PMID:The effect of 13 weeks of running training followed by 9 d of detraining on postprandial lipaemia. 979 44

To specify and localize carboxyl-terminal domain functions of human hepatic lipase (HL) and human lipoprotein lipase (LPL), two subdomain chimeras were created in which portions of the carboxyl-terminal domain were exchanged between the two lipases. The first chimera (HL-LPLC1) was composed of residues 1-344 of human HL, residues 331-388 of human LPL, and residues 415-476 of human HL. The second chimera (HL-LPLC2) consisted of just two segments, residues 1-414 of human HL and residues 389-448 of human LPL. These chimeric constructs effectively divided the HL C-terminal domain into halves, with corresponding LPL sequences either in the first or second portion of that domain. Both chimeras were lipolytically active and hydrolyzed triolein emulsions to a similar extent compared with native HL and LPL. Heparin-Sepharose chromatography demonstrated that HL-LPLC1 and HL-LPLC2 eluted at 0.80 and 1.3 M NaCl, respectively, elution positions that corresponded to native HL and LPL. Hence, substitution of LPL sequences into the HL carboxyl-terminal domain resulted in the production of functional lipases, but with distinct heparin binding properties. In addition, HL-LPLC2 trioleinase activity was responsive to apoC-II activation, although the -fold stimulation was less than that observed with native LPL. Moreover, an apoC-II fragment (residues 44-79) was specifically cross-linked to LPL and HL-LPLC2, but not to HL or HL-LPLC1. Finally, both chimeras hydrolyzed phospholipid with a specific activity similar to that of HL, which was unaffected by the presence of apoC-II. These findings indicated that in addition to a region found within the amino-terminal domain of LPL, apoC-II also interacted with the last half of the carboxyl-terminal domain (residues 389-448) to achieve maximal lipolytic activation. In addition, the relative heparin affinity of HL and LPL was determined by the final 60 carboxyl-terminal residues of each enzyme.
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PMID:Subdomain chimeras of hepatic lipase and lipoprotein lipase. Localization of heparin and cofactor binding. 981 94

Vascular endothelium-bound lipoprotein lipase (LPL) is rate limiting for free fatty acid (FFA) transport into tissues. In streptozotocin (STZ)-diabetic rats, we have previously demonstrated an increased heparin-releasable LPL activity from perfused hearts. Because heparin can traverse the endothelial barrier, conventional Langendorff retrograde perfusion of the heart with heparin could release LPL from both the capillary luminal and abluminal surfaces. To determine the precise location of the augmented LPL, a modified Langendorff retrograde perfusion was used to isolate the enzyme at the coronary lumen from that in the interstitial effluent. In response to heparin, a 4-fold increase in LPL activity and protein mass was observed in the coronary perfusate after 2 weeks of STZ diabetes. Release of LPL activity into the interstitial fluid of control hearts was slow but progressive, whereas in diabetic hearts, peak enzyme activity was observed within 1 to 2 minutes after heparin, followed by a gradual decline. Immunohistochemical studies of myocardial sections confirmed that the augmented LPL in diabetic hearts was mainly localized at the capillary endothelium. To study the acute effects of insulin on endothelial LPL activity, we examined rat hearts at various times after the onset of hyperglycemia. An increased heparin-releasable LPL activity in diabetic rats was demonstrated shortly (6 to 24 hours) after STZ injection or after withdrawal from exogenous insulin. Heparin-releasable coronary LPL activity was also increased after an overnight fast. These studies indicate that the intravascular heparin-releasable fraction of cardiac LPL activity is acutely regulated by short-term changes in insulin rather than glucose. Thus, during short periods (hours) of hypoinsulinemia, increased LPL activity at the capillary endothelium can increase the delivery of FFAs to the heart. The resultant metabolic changes could induce the subsequent cardiomyopathy that is observed in the chronic diabetic rat.
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PMID:Localization of lipoprotein lipase in the diabetic heart: regulation by acute changes in insulin. 1036 85

Hypertriglyceridaemia is thought to be the aetiology in 3% of patients with acute pancreatitis, often associated with poorly controlled diabetes mellitus or chronic alcohol abuse. However, in patients with non-biliary pancreatitis, chylomicronaemia is an underrated cause of acute pancreatitis. The activity of lipoprotein lipase (LPL) is crucial in removing triglycerides from the plasma; LPL gene mutations combined with secondary alterations in plasma lipoproteins, such as occur in pregnancy, diabetes mellitus, and alcohol abuse can cause severe hypertriglyceridaemia and pancreatitis. Heparin and insulin stimulate LPL activity. During a 12 months' period we consecutively screened all patients with the diagnosis of acute non-biliary pancreatitis for hypertriglyceridaemia, to evaluate the prevalence of hypertriglyceridaemia-induced pancreatitis and to assess the outcome under standardised treatment with intravenous heparin and insulin. Hypertriglyceridaemia-induced pancreatitis was diagnosed in 5 out of 46 patients (11%) with acute pancreatitis. In 2 patients hypertriglyceridaemia was associated with diabetes mellitus, in one patient with pregnancy and in another with chronic alcohol abuse. Four patients had to be referred to the intensive care unit. Plasma concentrations of triglycerides were (median +/- range) 43 mmol/l (14.7 to 80.4); pancreas amylase was 574 U/l (155 to 1606), and lipase was 1003 U/l (330 to 3010). All patients had oedematous pancreatitis demonstrated by CT scan. Treatment with i.v. heparin and i.v. insulin decreased trigylceride levels to less than 10 mmol/l within 2.8 days (1 to 6), the amylase and lipase levels returned to normal after 3 and 4 days respectively, and the abdominal pain was resolved. Hypertriglyceridaemia is a common and under-diagnosed etiology of acute non-biliary pancreatitis. Intravenous heparin and insulin is safe and effective in the treatment of hypertriglyceridaemia-induced pancreatitis. Low fat diet, supplements of (n-3) fatty acids ("fish oil") and fibrates are recommended for long-term maintenance therapy.
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PMID:[Heparin and insulin in the treatment of acute hypertriglyceridemia-induced pancreatitis]. 1049 50

Heparin given intravenously enhances lipolysis, although fasting lipids are not markedly altered in long-term administration. In the present study we investigated heparin-induced acute perturbation of VLDL subclass metabolism. Eight men were examined during a control study and during an 8.5 h infusion of heparin. 2H3-leucine was used as tracer and kinetic constants derived using a non-steady-state model. Heparin infusion increased both plasma lipoprotein and hepatic lipase activity and raised plasma FFAs two-fold (P < 0.001). The fractional catabolic rate (FCR) of VLDL1 apo B increased on heparin (25.7 +/- 4.2 and 10.8 +/- 1.7 pools/d, heparin vs. control, P < 0.02). The FCR of VLDL2 apo B increased to 12.6 +/- 1.9 pools/d on heparin vs. 8.8 +/- 1.1 pools/d during the control (NS). Total VLDL apo B production was not significantly changed (824 +/- 45 and 692 +/- 91 mg/d, heparin vs. control, NS). We conclude that during heparin infusion, the catabolism of especially large triglyceride-rich VLDL1 apo B is greatly increased. However, although the FFA levels were high during the heparin study, the production of total VLDL apo B did not rise. These findings are consistent with the known action of heparin on lipoprotein lipase but indicate that acute increase in plasma FFA levels does not lead to a rise in VLDL apo B production.
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PMID:Effect of heparin-stimulated plasma lipolytic activity on VLDL APO B subclass metabolism in normal subjects. 1053 94

Adipose tissue lipoprotein lipase (LPL) activity is decreased in patients with poorly controlled diabetes, and this contributes to the dyslipidemia of diabetes. To study the mechanism of this decrease in LPL, we studied adipose tissue LPL expression in male rats with streptozotocin-induced diabetes. Heparin releasable and extractable LPL activity in the epididymal fat decreased by 75-80% in the diabetic group and treatment of the rats with insulin prior to sacrifice reversed this effect. Northern blot analysis indicated no corresponding change in LPL mRNA levels. However, LPL synthetic rate, measured using [(35)S]methionine pulse labeling, was decreased by 75% in the diabetic adipocytes, and insulin treatment reversed this effect. These results suggested regulation of LPL at the level of translation. Diabetic adipocytes demonstrated no change in the distribution of LPL mRNA associated with polysomes, suggesting no inhibition of translation initiation. Addition of cytoplasmic extracts from control and diabetic adipocytes to a reticulocyte lysate system demonstrated the inhibition of LPL translation in vitro. Using different LPL mRNA transcripts in this in vitro translation assay, we found that the 3'-untranslated region (UTR) of the LPL mRNA was important in controlling translation inhibition by the cytoplasmic extracts. To identify the specific region involved, gel shift analysis was performed. A specific shift in mobility was observed when diabetic cytoplasmic extract was added to a transcript containing nucleotides 1818-2000 of the LPL 3'-UTR. Thus, inhibition of translation is the predominant mechanism for the decreased adipose tissue LPL in this insulin-deficient model of diabetes. Translation inhibition involves the interaction of a cytoplasmic factor, probably an RNA-binding protein, with specific sequences of the LPL 3'-UTR.
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PMID:The translational regulation of lipoprotein lipase in diabetic rats involves the 3'-untranslated region of the lipoprotein lipase mRNA. 1102 42

The maturation of lipoprotein lipase (LPL) into a catalytically active enzyme was believed to occur only after its transport from the endoplasmic reticulum (ER) to the Golgi apparatus. To test this hypothesis, LPL located in these two subcellular compartments was separated and compared. Heparin affinity chromatography resolved low affinity, inactive LPL displaying ER characteristics from a high affinity, active fraction exhibiting both ER and Golgi forms. The latter forms were further separated by beta-ricin chromatography and were found to have comparable activities per unit of LPL mass. Thus, LPL must reach a functional conformation in the ER. Active LPL, regardless of its cellular location, exhibited the expected dimer conformation. However, inactive LPL, found only in the ER, was highly aggregated. Kinetic analysis indicated a concurrent formation of LPL dimer and aggregate and indicated that the two forms have dissimilar fates. Whereas the dimer remained stable even when confined to the ER, the aggregate was degraded. Degradation rates were not affected by proteasomal or lysosomal inhibitors but were markedly reduced by ATP depletion. Lowering the redox potential in the ER by dithiothreitol caused the dimer to associate with calnexin, BiP, and protein-disulfide isomerase to form large, inactive complexes; dithiothreitol removal induced complex dissociation with restoration of the functional LPL dimer. In contrast, the LPL aggregate was only poorly associated with ER chaperones, appearing to be trapped in an irreversible, inactive conformation destined for ER degradation.
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PMID:Maturation of lipoprotein lipase in the endoplasmic reticulum. Concurrent formation of functional dimers and inactive aggregates. 3142 May 23

This work was designed to study the effect of different lipid sources on the activities of lipoprotein lipase and lipogenic enzymes in adipose tissue from rats fed ad libitum or energy-controlled diets. Male Wistar rats were fed diets containing 40% of energy as fat (olive oil, sunflower oil, palm oil or beef tallow), for 4 wk. Under ad libitum feeding no differences were found among dietary fat groups in final body weight, adipose tissue weights and total body fat. Under energy-controlled feeding, despite isoenergetic intake, rats fed the beef tallow diet gained significantly less weight than rats fed the other three diets. Beef tallow fed rats showed the lowest values for adipose tissue weights and total body fat. When rats had free access to food no effect of dietary lipid source on lipogenic enzyme activities was found. In contrast, under energy-controlled feeding rats fed the beef tallow diet showed significantly higher activities of glucose-6-phosphate dehydrogenase and fatty acid synthase than rats fed the other three diets. Heparin-releasable lipoprotein lipase activity in perirenal and subcutaneous adipose tissues was not different among rats fed olive oil, safflower oil, palm oil or beef tallow. When comparing both adipose tissue anatomical locations, significantly higher activities were found in subcutaneous than in perirenal fat pad independently of dietary fat. In conclusion, under our experimental protocol, lipogenesis in rat adipose tissue does not seem to be affected by dietary fat type.
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PMID:Lipoprotein lipase and lipogenic enzyme activities in adipose tissue from rats fed different lipid sources. 1180 Feb 87


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