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)

Interaction of purified bovine milk lipoprotein lipase (LpL) with sonicated vesicles of dipalmitoyl phosphatidylcholine in the gel phase is associated with an increase in the rate of the LpL-catalyzed hydrolysis of p-nitrophenyl butyrate. There is a 6-fold increase in Vmax. Apolipoprotein C-II, the activator protein for LpL, inhibits the LpL-catalyzed hydrolysis of p-nitrophenyl butyrate. With 0.5 mol % tri[14C]oleoylglycerol present in the dipalmitoyl phosphatidylcholine vesicles and in the presence of 20 mM Ca2+, the rate of p-nitrophenyl butyrate hydrolysis is decreased reciprocally compared to trioleoylglycerol hydrolysis and is dependent on apolipoprotein C-II. These results suggest that apolipoprotein C-II enhances the activity of LpL by increasing the affinity of the active site of LpL for triacylglycerol.
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PMID:Reciprocal effect of apolipoprotein C-II on the lipoprotein lipase-catalyzed hydrolysis of p-nitrophenyl butyrate and trioleoylglycerol. 710

During short-term incubation, a suspension of fat cells isolated from female rats hydrolyzed tri[3H]oleyl[14C]glycerol added as substrate and incorporated an average of 42% of the amounts of [3H]oleic acid released. Lipolysis was catalyzed by cell-bound lipoprotein lipase (LPL), whose activity was influenced by apoproteins (apo) C purified from human plasma. ApoC-II enhanced 12-fold the hydrolysis rates with cells from fed rats versus 3,4-fold with cells from fasted rats. In both cases, the stimulation by apoC-II was greater than that by whole serums from led or fasted rats. Maximal LPL activity at the cell surface depended more on the preexisting nutritional state of the cell than on apoC-II or serums added extracellular. ApoC-I, apoC-III1 and apoC-III2 had no or moderate direct effects on LPL activity, whereas apoC-III1 and apoC-III2 reduced markedly the stimulating effect of apoC-II. At all levels of LPL activity, the amounts of [3H]oleic acid liberated by hydrolysis and incorporated as [3H]acylglycerol in cell lipids were highly correlated with LPL activity, suggesting that the uptake process was directly related to enzyme action.
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PMID:Effects of apoproteins C on lipoprotein lipase activity bound to rat fat cells. 711 50

Apolipoprotein C-II, which activates lipoprotein lipase, was isolated from normal subjects and purified to homogeneity by reverse-phase high-pressure liquid chromatography (HPLC). The partially purified product from DEAE-cellulose chromatography was eluted from a Radial Pak C18 cartridge in a radial compression module using a linear gradient of 0.01 M ammonium bicarbonate and acetonitrile. The final product was homogeneous by polyacrylamide gel electrophoresis (pH 8.9), isoelectric focusing (pH 2.5-6.5), Ouchterlony double immunodiffusion, analytical HPLC and amino acid analysis. The purification of apolipoprotein C-II from normal subjects will permit the elucidation of its amino acid sequence and subsequent comparison with the known sequence of apolipoprotein C-II isolated from patients with hyperlipoproteinemia.
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PMID:Purification and characterization of apolipoprotein C-II from human plasma by high-pressure liquid chromatography. 715 Jun 33

Bovine milk lipoprotein lipase (LpL) catalyzes the hydrolysis of the water-soluble esters p-nitrophenyl acetate (PNPA) and p-nitrophenyl butyrate (PNPB). The same protein and same active site are involved in hydrolysis of water-soluble p-nitrophenyl esters and emulsified trioleoylglycerol since (a) trioleoylglycerol hydrolysis and PNPB hydrolysis activities coelute from the heparin-Sepharose affinity column used to purify LpL and (b) LpL-catalyzed hydrolyses of trioleoylglycerol and PNPB are inhibited to equal extents by phenylmethanesulfonyl fluoride. The effect of apolipoprotein C-II (apoC-II) on the LpL-catalyzed hydrolysis of PNPA and PNPB has been determined. ApoC-II inhibits hydrolysis of both esters, with a maximum extent of inhibition of 70-90%. Inhibition of the LpL-catalyzed hydrolysis of PNPB is specific for apoC-II, since apolipoproteins A-I, C-I, and C-III-2 have little effect on this reaction, and is partial noncompetitive in form. KI values for apoC-II inhibition of the LpL-catalyzed hydrolysis of PNPA and PNPB are in the range 0.26-0.83 microM. The effect of apoC-II on the temperature dependences of LpL-catalyzed hydrolysis of both esters and on NaCl inhibition of LpL-catalyzed PNPB hydrolysis is consistent with a change in rate-determining step with LpL and apoC-II interact. These results indicate not only that there is an interaction between apoC-II and LpL in aqueous solution in the absence of a lipid interface but also that this interaction conformationally modulates the active site of the enzyme.
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PMID:Lipoprotein lipase catalyzed hydrolysis of water-soluble p-nitrophenyl esters. Inhibition by apolipoprotein C-II. 715 70

Mild tryptic digestion of lipoprotein lipase cleaved its polypeptide chain in the middle, but the pieces were held together by disulphide bonds. The modified enzyme retained its ability to bind to heparin and to anionic detergents and on gel filtration it eluted in a similar position as the native enzyme does. It also retained essentially full activity against soluble substrates. Thus, the overall physico-chemical properties of the enzyme were not markedly changed and its active site remained intact after treatment with trypsin. The activity of the modified enzyme against long-chain acylglycerols and phospholipids was, however, much reduced. With some emulsions, the decreased activity could be ascribed in part to a decreased ability of the modified enzyme to bind to the emulsion droplets. Under these conditions apolipoprotein CII partially restored both binding and activity. With a lysophosphatidylcholine-triacylglycerol emulsion the modified enzyme adsorbed almost completely to the emulsion droplets, but its activity was nonetheless very low. Thus, tryptic cleavage interfered with the ability of the enzyme to become properly orientated at the interface. With this emulsion apolipoprotein CII enhanced the activity of the native enzyme fourfold but the activity of the trypsin-treated enzyme 30-fold, so that the activity of the modified enzyme became almost as high as that of the native enzyme. It is concluded that apolipoprotein CII enhances the activity of lipoprotein lipase by stabilizing an effective orientation/conformation of the enzyme at the interface. This effect became more marked when the ability of the enzyme itself to attain this form had been reduced by tryptic cleavage.
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PMID:Lipoprotein lipase: modification of its kinetic properties by mild tryptic digestion. 721 41

Very low density lipoproteins isolated from guinea pig liver perfusate (VLDLp) lack the equivalent of human apolipoprotein C-II (apoC-II), the activator of lipoprotein lipase (LpL). These lipoproteins are therefore ideal substrates with which to investigate the mechanism by which apoC-II activates the enzyme. VLDLp binds apoC-II, and apoC-II associated with VLDLp markedly increases the rate of lipoprotein lipase-catalyzed hydrolysis of VLDLp-triglycerides. The activator potency of apoC-II is independent of the method of enrichment of VLDLp with apoC-II: delipidated human apoC-II and apoC-II transferred from human high density lipoproteins activate lipoprotein lipase to equal extents. ApoC-II causes pH-dependent changes in both apparent Km and VmaX of LpL-catalyzed hydrolysis of VLDLp-triglycerides. At pH l7.4--7.5, the major effects of apoC-II is to decrease the apparent Km by 3.3--4.0 fold. The apparent Vmax is increased 1.3-fold. At pH 6.5 and 8.5, the decrease of apparent Km is less marked, 1.6-fold and 1.4-fold, respectively. At pH 6.5, apoC-II increases the apparent Vmax ty 1.3-fold, while at pH 8.5 the primary effect of apoC-II is a 1.6-fold increase of apparent Vmax. Based on a simple kinetic model, the data suggest that apoC-II favors direct interaction between enzyme and triglyceride within the lipoprotein particle, as well as subsequent catalytic turnover.
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PMID:Hydrolysis of guinea pig nascent very low density lipoproteins catalyzed by lipoprotein lipase: activation by hjman apolipoprotein C-II. 727 52

This paper considers how apolipoprotein CII from human plasma lipoproteins and T1 and T2 proteins from egg yolk lipoproteins stimulate the activity of lipoprotein lipase. These activator proteins stabilized the enzyme much more effectively than a thousandfold higher concentration of albumin did, indicating a direct interaction with the enzyme. The effects of the activators were seen also at 1 M NaCl. Thus, forces other than electrostatic are implicated. Centrifugation experiments showed that 125I-labeled lipase bound equally well to the emulsion droplets in the absence of activator protein as in its presence. This was true even under conditions when the activator caused a severalfold increase in the rate of hydrolysis. Thus, the activator makes enzyme at the interface more effective in hydrolysis. By optimizing the conditions it was possible to obtain almost as high rates of triglyceride hydrolysis in the absence as in the presence of activator. Thus, the main effect of the activator protein is probably not on a rate-limiting chemical step. Under most conditions, the rate of hydrolysis was much below optimal and activator increased it. This was always the case with phosphatidyl-choline/triglyceride emulsions, where the activator enhanced hydrolysis of both lipids. Other experiments showed that the activator enhanced triglyceride hydrolysis in the absence of phospholipids and phospholipid hydrolysis in the absence of triglycerides. It is suggested that interaction with activator orientates the enzyme and/or the lipid substrate for effective hydrolysis at the surface of lipoproteins/model substrates.
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PMID:Lipoprotein lipase: some effects of activator proteins. 739 26

Purified bovine milk lipoprotein lipase has been covalently attached to CH-Sepharose with water-soluble carbodiimide. The immobilized enzyme retained enzymic activity and was stimulated 7-fold by the addition of human apolipoprotein C-II. Both [3H]heparin and 125I-labeled apolipoprotein C-II bound to the immobilized enzyme; unlabeled heparin and apolipoprotein C-II competed for binding of their respective labeled compounds. Apolipoprotein C-II did not compete for binding of [3H]heparin and vice versa. Human apolipoprotein C-III did not bind to the immobilized enzyme nor did it compete for apolipoprotein C-II binding. We conclude from these studies that both apolipoprotein C-II and heparin interact with immobilized lipoprotein lipase and that they have different binding sites.
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PMID:Preparation and properties of immobilized lipoprotein lipase. 743 56

In this paper we report on the molecular defect underlying apolipoprotein CII (apoCII) deficiency in an Italian kindred. ApoCII serves as cofactor for lipoprotein lipase (LPL) in triglyceride hydrolysis of chylomicrons and very low density lipoproteins. Homozygous apoCII deficiency manifests with type I hyperlipoproteinaemia and is a rare disorder of lipoprotein metabolism. Until now, only 10 kindreds with apoCII deficiency have been published and all underlying mutations were unique. The proband was the offspring of a consanguineous mating. Sequencing of cloned DNA from the proband presented in this report showed homozygosity for a C-->A substitution at position 3002 in the apoCII gene, resulting in the introduction of a premature stop codon at residue 37 of the mature apoCII protein. Therefore, a truncated apoCII is synthesised, lacking the part of the apolipoprotein that activates LPL. This mutation has previously been described in another Italian family and is known as apoCIIPadova. We propose that apoCIIPadova is a frequent cause of apoCII deficiency in persons of Italian descent.
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PMID:Apolipoprotein CII-Padova (Tyr37-->stop) as a cause of chylomicronaemia in an Italian kindred from Siculiana. 781 20

The reduced lipoprotein lipase (LPL) activities in uraemia are reflected by increased serum triglyceride concentrations and reduced HDL cholesterol concentrations. Both hyperparathyroidism and circulating inhibitor(s) of LPL have been associated with the disturbances of lipid metabolism in uraemia. The aim of the present study was to investigate if parathyroid hormone (PTH) had an inhibitory effect on LPL activity. Plasma post-heparin LPL activities, plasma LPL inhibitory activities, serum PTHintact and serum PTHC-terminal concentrations were analysed in 20 patients on haemodialysis and 20 healthy controls. The effects of purified, human PTHintact and a carboxyterminal fragment of PTH (PTH39-84) on LPL activities in post-heparin plasma from healthy individuals and on the enzyme activity of purified, bovine milk LPL, activated with apolipoprotein CII, were studied. Patients had significantly higher plasma LPL inhibitory activities than controls, but there was no correlation between plasma LPL inhibitory activities and serum PTH concentrations. Neither PTHintact nor PTH39-84 had a significant effect on LPL activities in vitro. Thus there was no evidence of a direct inhibition of LPL activity by PTH under the present in-vivo or in-vitro conditions.
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PMID:Parathyroid hormone is not an inhibitor of lipoprotein lipase activity. 859 13


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