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 triacylglycerol hydrolyase and phospholipase A1 activities of bovine milk lipoprotein lipase toward long-chain fatty acyl ester substrates were investigated with monomolecular lipid films containing trioleoylglycerol and phosphatidylcholine. In a monolayer of egg phosphatidylcholine containing 3 mol% [14C]trioleoylglycerol, and in the presence of apolipoprotein C-II, a 79 amino acid activator protein for lipoprotein lipase, enzyme activity was maximal at a surface pressure of 21-22 mN X m-1 (37 mumol oleic acid released/h per mg enzyme); enzyme activity was enhanced 9-fold by apolipoprotein C-II. At surface pressures between 22 and 30 mN X m-1, lipoprotein lipase activity decreased over a broad range and was nearly zero at 30 mN X m-1. Apolipoprotein C-II and the synthetic fragments of the activator protein containing residues 56-79, 51-79 and 44-79 were equally effective at 20 mN X m-1 in enhancing lipoprotein lipase catalysis. However, at surface pressures between 25 and 29 mN X m-1, only apolipoprotein C-II and the phospholipid-associating fragment containing residues 44-79 enhanced enzyme catalysis. The effect of apolipoprotein C-II and synthetic peptides on the phospholipase A1 activity of lipoprotein lipase was examined in sphingomyelin:cholesterol (2:1) monolayers containing 5 mol% di[14C]myristoylphosphatidylcholine. At 22 mN X m-1, apolipoprotein C-II and the synthetic fragments containing residues 44-79 or 56-79 enhanced lipoprotein lipase activity (70-80 nmol/h per mg enzyme). In contrast to trioleoylglycerol hydrolysis, the synthetic fragments were not as effective as apolipoprotein C-II enhancing enzyme activity towards di[14C]myristoylphosphatidylcholine at higher surface pressures. We conclude that the minimal amino acid sequence of apolipoprotein C-II required for activation of lipoprotein lipase is dependent both on the lipid substrate and the packing density of the monolayer.
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PMID:Interaction of synthetic peptides of apolipoprotein C-II and lipoprotein lipase at monomolecular lipid films. 394 62

The effect of apolipoproteins C-II and C-III on the lipoprotein lipase-catalyzed hydrolysis of apolipoprotein C-II-deficient triacylglycerol-rich lipoproteins and particles of trioleoylglycerol stabilized with a phosphatidylcholine monolayer was investigated. For both triacylglycerol-rich lipoproteins and artificial lipid particles, maximal lipoprotein lipase activity occurred at a constant apolipoprotein C-II/phospholipid mol ratio of 2.0 X 10(-4) and was independent of particle size, indicating that the amount of apolipoprotein C-II bound to the surface of the substrate is important for enzyme activation. The effect of apolipoprotein C-II on lipoprotein lipase activity with apolipoprotein C-II-deficient lipoproteins as substrate was to decrease the apparent Michaelis constant (Kmapp) from 7.1 to 1.0 mM with minor changes on the apparent maximal velocity (Vmax) (22.2 mmol free fatty acid released/h per mg enzyme). In contrast, apolipoprotein C-II increased the apparent Vmax from 2.4 to 20.0 mmol free fatty acid/h per mg enzyme for the lipoprotein lipase-catalyzed hydrolysis of trioleoylglycerol/phospholipid particles with little change in Kmapp (1.0 mM). Addition of apolipoprotein C-II-deficient triacylglycerol-rich lipoproteins or high-density lipoproteins to trioleoylglycerol/phospholipid particles in the presence of apolipoprotein C-II inhibited lipoprotein lipase activity. Lipoprotein lipase activity was also inhibited by the addition of a large excess of lipid-free apolipoprotein C-III to the artificial particles. The decrease in lipoprotein lipase activity correlated with the amount of bound apolipoprotein C-II. We suggest that the reported discrepancies on the effect of apolipoproteins C-II and C-III on lipoprotein lipase catalysis is related to differences in substrates and to the amount of added apolipoproteins.
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PMID:Comparison of apolipoprotein C-II-deficient triacylglycerol-rich lipoproteins and trioleoylglycerol/phosphatidylcholine-stabilized particles as substrates for lipoprotein lipase. 394 63

We have isolated an isoform of the protein activator of lipoprotein lipase, apolipoprotein C-II, from the very low density lipoproteins of four patients of African ancestry with hypertriglyceridemia and eruptive or pedunculated xanthomata. This protein, which we designate apolipoprotein C-II2, differs from the previously recognized species, which we denote apolipoprotein C-II1, by substitution of glutamine for lysine at residue 55, a mutation which would require only a single-base substitution in the structural gene for apolipoprotein C-II1. Each of the patients in whom apolipoprotein C-II2 was found had approximately equal amounts of apolipoprotein C-II1 and apolipoprotein C-II2 among the apoproteins of the very low density lipoproteins, suggesting that the structural genes for these proteins are allelic. Two additional apparent heterozygotes were found among the first-degree relatives of each of two of the patients in patterns compatible with monogenic autosomal transmission. Approximately equal amounts of apolipoproteins C-II2 and C-II1 were also found by isoelectric focusing in 6 of a casual series of 50 normolipidemic blacks, but none or only trace amounts of apolipoprotein C-II2 were found in 500 samples from Caucasian subjects with hyperlipidemia. These findings suggest that this polymorphism is distributed primarily among blacks, possibly reflecting some positive Darwinian selection pressure. Whether this polymorphism has a modifying effect upon the development of hyperlipemia remains to be determined.
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PMID:A variant primary structure of apolipoprotein C-II in individuals of African descent. 394 71

The kinetics of human and bovine milk lipoprotein lipase (HM-LPL and BM-LPL, respectively) were compared by varying apolipoprotein C-II (C-II) or triacylglycerol (TG) concentrations. The apparent Km (TG) and Km (C-II) for HM-LPL were 2.2 and 6.7-fold higher than for BM-LPL. Plots of 1/v vs 1/[TG] or 1/[C-II] intercepted the respective abscissas at the same points: C-II had no effect on Km (TG) and TG had no effect on Km (C-II). Replots of slope 1/s vs 1/[C-II] gave straight lines which yielded KA values identical to Km (C-II). It is concluded that the HM-LPL system follows a random, bireactant, rapid equilibrium mechanism as shown previously for BM-LPL.
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PMID:Kinetics of human and bovine milk lipoprotein lipase and the mechanism of enzyme activation by apolipoprotein C-II. 396 87

Ten murine monoclonal antibodies have been produced that are specific for bovine milk lipoprotein lipase. One monoclonal antibody, bLPL-mAb-7, inhibited completely the apolipoprotein C-II (apo-C-II)-dependent enzymic hydrolysis of trioleoylglycerol in a phospholipid-stabilized emulsion, but had no effect on the hydrolysis of the water-soluble substrate p-nitro-phenylacetate. Four times more bLPL-mAb-7 was required to achieve 50% inactivation of lipoprotein lipase activity when the enzyme was preincubated with excess apo-C-II. Disruption of the binding of a dansyl-labeled apo-C-II peptide to lipoprotein lipase by bLPL-mAb-7 was demonstrated by resonance energy transfer, both in the presence and absence of lipid. This antibody thus appears to recognize the apo-C-II binding site of lipoprotein lipase. In addition, bLPL-mAb-7 also inhibited the lipoprotein lipase activity of human post-heparin plasma.
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PMID:Monoclonal antibodies against bovine milk lipoprotein lipase. Characterization of an antibody specific for the apolipoprotein C-II binding site. 396 71

The binding of lipoprotein lipase to a fluorescently labelled apolipoprotein C-II in free solution has been followed by measuring fluorescence anisotropy. The formation of a weak, binary complex in which a single apolipoprotein C-II molecule associates non-cooperatively with each subunit of the dimeric enzyme was observed. The dissociation constant for this complex in 0.05 M NaCl is 0.2 X 10(-6) M and it is weakened markedly by raising the salt concentration and by the binding of heparin to the enzyme. The assembly of the same protein-protein complex on the surface of glycerol trioleate globules has been monitored by steady-state and pre-steady-state kinetics. In these circumstances the lipoprotein lipase-apolipoprotein C-II interaction is much tighter (Kd = (7-10) X 10(-9) M) and is insensitive to salt and heparin. The mechanism of activation of the enzyme at low concentrations of apolipoprotein C-II is described by a kinetic model in which apolipoprotein C-II binds preferentially to the form of the enzyme which is associated with the triacylglycerol substrate. This preference leads to a stabilization of the enzyme-substrate complex, thus reducing the apparent Ks.
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PMID:The mechanism of activation of lipoprotein lipase by apolipoprotein C-II. The formation of a protein-protein complex in free solution and at a triacylglycerol/water interface. 397 Sep 43

The phospholipase A1 activity of lipoprotein lipase (LpL) was determined with monomolecular phospholipid films. Rates of phospholipid hydrolysis were dependent on apolipoprotein C-II (the activator protein for LpL) phospholipid fatty acyl composition, and lipid-packing density. In sphingomyelin: cholesterol (2:1, molar) monolayers containing 5 mol % disaturated phosphatidylcholines (PC) and at a surface pressure of 22 mNm-1, rates of LpL hydrolysis of diC14:0PC, diC16:0PC, and diC18:0PC were 74, 207, and 65 nmol h-1 mg LpL-1, respectively. At 22 mNm-1, phospholipids containing unsaturated fatty acyl chains were hydrolyzed at rates 5-10 times greater than saturated lipids. At higher lipid packing densities, the difference in hydrolysis rates between saturated and unsaturated lipids was less apparent. Comparison of molecular areas indicate no simple dependency between the rate of LpL catalysis and phospholipid fatty acyl chain length and saturation/unsaturation.
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PMID:Lipoprotein lipase-catalyzed hydrolysis of phospholipid monolayers: effect of fatty acyl composition on enzyme activity. 399 18

Like rat C apolipoproteins, each of the C apolipoproteins from human blood plasma (C-I, C-II, C-III-1, and C-III-2) bound to small chylomicrons from mesenteric lymph of estradiol-treated rats and inhibited their uptake by the isolated perfused rat liver. This inhibitory effect of the C apolipoproteins was independent of apolipoprotein E, which is present only in trace amounts in these chylomicrons. Addition of rat apolipoprotein E to small chylomicrons from mesenteric lymph of normal rats did not displace C apolipoproteins and had no effect on the uptake of these particles by the perfused liver, indicating that an increased ratio of E apolipoproteins to C apolipoproteins on chylomicron particles, unaccompanied by depletion of the latter, may not promote recognition by the chylomicron remnant receptor. The hepatic uptake of remnants of rat hepatic very low density lipoproteins (VLDL) and small chylomicrons, which had been produced in functionally eviscerated rats, was also inhibited by addition of C apolipoproteins. These observations are consistent with the hypothesis that the addition of all of the C apolipoproteins to newly secreted chylomicrons and VLDL inhibits premature uptake of these particles by the liver and that depletion of all of these apolipoproteins from remnant particles facilitates their hepatic uptake. Remnants of chylomicrons and VLDL incubated with rat C apolipoproteins efficiently took up C-III apolipoproteins, but not apolipoprotein C-II (the activator protein for lipoprotein lipase). Preferential loss of apolipoprotein C-II during remnant formation may regulate the termination of triglyceride hydrolysis prior to complete removal of triglycerides from chylomicrons and VLDL.
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PMID:Inhibitory effects of C apolipoproteins from rats and humans on the uptake of triglyceride-rich lipoproteins and their remnants by the perfused rat liver. 402 Feb 94

The interaction of lipoprotein lipase (LpL) and its activator protein, apolipoprotein C-II (apoC-II), with a nonhydrolyzable phosphatidylcholine, 1,2-ditetradecyl-rac-glycero-3-phosphocholine (C14-ether-PC), was studied by fluorescence spectroscopy. A complex of 320 molecules of C14-ether-PC per LpL was isolated by density gradient ultracentrifugation in KBr. The intrinsic tryptophan fluorescence emission spectrum of LpL was shifted from 336 nm in the absence of lipid to 330 nm in the LpL-lipid complex; the shift was associated with a 40% increase in fluorescence intensity. Addition of C14-ether-PC vesicles to apoC-II caused a 2.5-fold increase in intrinsic tryptophan fluorescence and a shift in emission maximum from 340 to 317 nm. LpL and apoC-II/C14-ether-PC stoichiometries and binding constants were determined by measuring the increase in the intrinsic tryptophan fluorescence as a function of lipid and protein concentrations; for LpL the rate and magnitude of the fluorescence increases were relatively independent of temperature in the range 4-37 degrees C. A stoichiometry of 270 PC per LpL for the LpL-lipid complex compares favorably with the value obtained in the isolated complex. The dissociation constant (Kd) of the complex is 4.3 X 10(-8) M. For apoC-II, the stoichiometry of the complex is 18 PC per apoprotein, and the Kd is 3.0 X 10(-6) M. These data suggest that LpL binds more strongly than apoC-II to phosphatidylcholine interfaces.
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PMID:Interaction of lipoprotein lipase and apolipoprotein C-II with sonicated vesicles of 1,2-ditetradecylphosphatidylcholine: comparison of binding constants. 405 89

Rabbit antiserum was prepared against purified bovine mild lipoprotein lipase. Immunoelectrophoresis of lipoprotein lipase gave a single precipitin line against the antibody which was coincident with enzyme activity. The gamma-globulin fraction inhibited heparin-releasable lipoprotein lipase activity of bovine arterial intima, heart muscle and adipose tissue. The antibody also inhibited the lipoprotein lipase activity from adipose tissue of human and pig, but not that of rat and dog. Fab fragments were prepared by papain digestion of the gamma-globulin fraction. Fab fragments inhibited the lipoprotein lipase-catalyzed hydrolysis of dimyristoylphosphatidylcholine vesicles and trioleoylglycerol emulsions to the same extent. The Fab fragments also inhibited the lipolysis of human plasma very low density lipoproteins. The change of the kinetic parameters for the lipoprotein lipase-catalyzed hydrolysis of trioleoylglycerol by the Fab fragments was accompanied with a 3-fold increase in Km and a 10-fold decrease in Vmax. Preincubation of lipoprotein lipase with apolipoprotein C-II, the activator protein for lipoprotein lipase, did not prevent inhibition of enzyme activity by the Fab fragments. However, preincubation with dipalmitoylphosphatidylcholine-emulsified trioleoylglycerol or Triton X-100-emulsified trioleoylglycerol had a protective effect (remaining activity 7.0 or 25.8%, respectively, compared to 1.0 or 0.4% with no preincubation). The addition of both apolipoprotein C-II and substrate prior to the incubation with the Fab fragments was associated with an increased protective effect against inhibition of enzyme activity; remaining activity with dipalmitoylphosphatidylcholine-emulsified trioleoylglycerol was 40.6% and with Triton X-100-emulsified trioleoylglycerol, 45.4%. Human plasma very low density lipoproteins also protected against the inhibition of enzyme activity by the Fab fragments. These immunological studies suggest that the interaction of lipoprotein lipase with apolipoprotein C-II in the presence of lipids is associated with a conformational change in the structure of the enzyme such that the Fab fragments are less inhibitory. The consequence of a conformational change in lipoprotein lipase may be to facilitate the formation of an enzyme-triacylglycerol complex so as to enhance the rate of the lipoprotein lipase-catalyzed turnover of substrate to products.
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PMID:Immunological studies on bovine milk lipoprotein lipase. Effects of Fab fragments on enzyme activity. 618 Jul 71


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