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 metabolic origins of equine hyperlipaemia were investigated by analysing the concentration and composition of plasma lipoproteins in 18 ponies with the condition. The mean concentrations of cholesterol, triglyceride and very low density lipoproteins (VLDL) were increased by 4-, 52- and 19-fold, respectively, compared with a control group of 18 healthy ponies. These increases were due to the appearance of a buoyant VLDL fraction (VLDL1) not present in healthy ponies. The mean diameter of VLDL1 particles was 44% greater than control VLDL, and the particles were enriched in triglyceride and free cholesterol and depleted of cholesteryl esters, phospholipid and protein. The apolipoprotein (apo) B-100 content of VLDL1 was reduced and the ratio of apoB-100 to apoB-48 particles was 1:1, compared with 2:1 in control VLDL. The VLDL1 was also enriched in apoE, but had normal complements of apoC-II and apoC-III. The conventional VLDL (called VLDL2), LDL and HDL fractions were moderately enriched with triglyceride, and HDL contained increased amounts of apoE, apoC-II and apoC-III. The activities of lipoprotein lipase and hepatic lipase, the enzymes responsible for the catabolism of VLDL and their remnants, were increased by 2- and 3-fold, respectively, in response to the increased concentrations of their substrates. The composition of VLDL1 suggested that the liver was maximising the secretion of triglyceride by producing larger number of VLDL particles that accommodated a greater mass of triglyceride by having apoB-48 rather than apoB-100 as their structural protein. Plasma free fatty acid (FFA) concentrations were elevated in 17 of the 18 ponies, suggesting that increased FFA flux might be the stimulus for hepatic triglyceride synthesis and VLDL secretion. We conclude that overproduction, rather than defective catabolism, of VLDL was the cause of the hyperlipidaemia and that lipid lowering agents which reduce VLDL synthesis, by decreasing adipose lipolysis and FFA flux, are candidates for the management of hyperlipaemia.
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PMID:Plasma lipids, lipoproteins and post-heparin lipases in ponies with hyperlipaemia. 139 7

The aims of the present study were to evaluate the metabolism of chylomicrons (CM) and of CM remnants after labelling with radioactive iodine and converting the iodinated CM into remnants in vitro. Lymph CM were radiolabelled with 125I or sham-labelled with 127I by either the ICl procedure or the tyramine-cellobiose (TC) procedure, then injected into rats. The clearance from plasma of the iodinated CM was compared with control non-iodinated lipid-labelled CM. After iodination with ICl, the plasma removal of endogenously labelled CM was significantly different from non-iodinated CM, with increased uptake of CM triacylglycerols by the liver. In contrast, the clearances from plasma and the uptake by organs of radiolabelled lipids of CM iodinated by the TC method (TC-CM) were similar to control CM. About 40% of the label from 125I-TC-CM was insoluble in 50% propan-2-ol, indicating association with CM apolipoprotein B48. Only about 8% of label was lipid soluble, mostly in phosphatidylethanolamine. Radioactivity from 125I-TC-CM injected intravenously in rats was cleared rapidly and by 30 min only 20% remained in plasma, whereas 48% was recovered in the liver. After fractionation of the plasma by density-gradient ultracentrifugation, most label remained associated with d (relative density) less than 1.006 lipoproteins. In intact rats label was also found associated with the low-density and high-density lipoprotein fractions of plasma. When the liver was excluded from circulation, the recovery of label in low-density- and high-density-lipoprotein fractions was greatly decreased. CM remnants were prepared in vivo by injecting 125I-TC-CM into functionally hepatectomized donors and compared with remnants prepared in vitro by incubation with purified bovine milk lipoprotein lipase. Although remnants prepared in vitro cleared from plasma slower than remnants prepared in vivo, the size, lipid composition and apolipoprotein profile on gradient PAGE of the remnants were similar. We conclude that labelling of CM by the TC method avoided the 'artefactual' changes in metabolism seen after labelling by the ICl procedure. CM remnants when prepared in vitro using lipoprotein lipase were found to be similar to those prepared in vivo after injection into functionally hepatectomized rats.
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PMID:Clearance from plasma of lymph chylomicrons and chylomicron remnants labelled with 125I-tyramine-cellobiose. 141 53

A monoclonal antibody to apolipoprotein (apo) B-100 (JI-H) with unique binding properties has been used to separate a population of triglyceride-rich lipoproteins from blood plasma of normotriglyceridemic individuals and patients with various forms of hypertriglyceridemia. This antibody fails to recognize an apoE-rich population of very low density lipoproteins (VLDL) containing apoB-100 as well as all triglyceride-rich lipoproteins containing apoB-48, but it binds other VLDL that contain apoE and almost all lipoproteins that contain apoB-100, but no apoE. The unbound triglyceride-rich lipoproteins separated by ultracentrifugation after separation from plasma by immunoaffinity chromatography contained 10-13% of the apoB of triglyceride-rich lipoproteins from three normotriglyceridemic individuals, 10-29% of that from five patients with endogenous hypertriglyceridemia, 40-48% of that from three patients with familial dysbetablipoproteinemia, and 65% of that from a patient with lipoprotein lipase deficiency. In all cases, the unbound triglyceride-rich lipoproteins contained more molecules of apoE and cholesteryl esters per particle than those that were bound to monoclonal antibody JI-H, and they were generally depleted of C apolipoproteins. These properties resemble those described for partially catabolized remnants of chylomicrons and VLDL. The affinity of the unbound lipoproteins for the low density lipoprotein (LDL) receptor varied widely, and closely resembled that of the total triglyceride-rich lipoproteins from individual subjects. Our results demonstrate that remnant-like chylomicrons and a population of remnant-like VLDL can be isolated and quantified in blood plasma obtained in the postabsorptive state from normotriglyceridemic and hypertriglyceridemic individuals alike.
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PMID:Properties of an apolipoprotein E-enriched fraction of triglyceride-rich lipoproteins isolated from human blood plasma with a monoclonal antibody to apolipoprotein B-100. 156 86

Endogenous apolipoprotein E in VLDL is poorly expressed in receptor binding processes. Yet catabolism of VLDL-remnants by cellular receptors depends on functional apo E molecules. To better understand remnant catabolism phenomena, we determined the metabolism of VLDL and post-lipolysis VLDL by cultured cells. Partial lipolysis was achieved by incubation of VLDL with lipoprotein lipase in vitro (human) or recirculation (rat) in supradiaphragmatic animals. Lipolyzed VLDL exhibit metabolic activities 2-20-fold higher than control VLDL, that are saturable and dependent on the presence of LDL receptors. The ligand responsible for receptor interaction of lipolyzed VLDL (apo E or apo B-100) and its source (endogenous or transferred) was studied with monoclonal antibodies and with lipoproteins from E-3/3 and E-2/2 subjects. The data unequivocally proved that lipolysis causes exposure of unreactive endogenous apo E-3 at the VLDL surface, possibly by a change of conformation of the protein. Apo B-100 becomes biologically expressed only in lipolyzed VLDL-III. Lipolyzed VLDL, however, is less reactive to exogenous apo E-3 than control VLDL indicating that endogenous and exogenous apo E are oriented differently in VLDL. It is proposed that VLDL delivers triglycerides to tissues when apo E is unreactive but becomes a remnant after the protein becomes exposed and directs the particles from lipoprotein lipase sites to cellular receptors.
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PMID:Lipolysis exposes unreactive endogenous apolipoprotein E-3 in human and rat plasma very low density lipoprotein. 186 65

Our primary aim was to determine the extent to which intraplasmic retinyl palmitate (RP) transfers to other lipoprotein particles when chylomicron remnants are not produced and/or the plasma RP residence time is increased. The study was conducted on three familial type I hyperlipoproteinemic patients, four lipoprotein lipase (LpL)-deficient heterozygotes, and three controls on a metabolic research unit. To each subject, a fat load was administered containing 16% of total daily calories in type I patients, 40% in heterozygotes and controls, plus 60,000 U/m2 vitamin A. Triglyceride (TG) and RP levels were evaluated in chylomicron and nonchylomicron fractions. Delay in the clearance of chylomicron fraction RP and the marked deficiency in nonchylomicron-RP (presumed lack of remnant production) in all three type I patients suggests that RP does not demonstrate significant intraplasmic transfer from chylomicrons to existent apolipoprotein B100 particles. In contrast to noncoincident TG and RP peaking in the normal subject, heterozygotes were found to demonstrate coincident plasma TG and RP curves, which is consistent with a common catabolic pathway for both TG and RP and inconsistent with intraplasmic RP transfer. This corroborates reports on compromised chylomicron clearance in heterozygotes. We conclude that RP is an appropriate representative marker for intestinally derived particles in LpL-deficient or partially deficient individuals.
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PMID:Chylomicron-retinyl palmitate clearance in type I hyperlipidemic families. 188 83

Intestinal apolipoproteins play a major role in lipoprotein metabolism. Apolipoproteins (Apo) AI, AIV and B48 are synthesized with chylomicrons in the mucosa and secreted into intestinal lymph. Apo B48 and B100 are coded for by the same gene on chromosome 2 and are identical in their aminoterminus. While apo B100 mRNA can be translated to the 4536 amino acid protein, the apo B48 mRNA is edited to contain a stopcodon at amino acid 2152. Apo B48 seems to be important for the secretion of chylomicrons and stays with chylomicrons during their lipolysis in plasma. Hydrolysis only takes place after the particle has acquired apo CII, the obligate cofactor for the enzyme lipoprotein lipase. The ligand for final irreversible uptake into the liver, mediated by a putative chylomicron-remnant receptor, seems to be apo E which only associates during lipolysis in plasma. Although apo E is not synthesized to a significant extent in the gut it was reported to influence intestinal cholesterol absorption: carriers of the genetic apo E2 isoform seem to absorb cholesterol to a lesser extent than those with apo E4 as compared to apo E3. Despite the almost exclusive synthesis of apo AIV and the significant extent of apo AI synthesis in the human gut these two apoproteins do not seem to have a chylomicron specific function. They seem to be more involved in the "reversed cholesterol transport", believed to be antiatherogenic. After entering the plasma compartment apo AI and AIV leave the chylomicrons during lipolysis as "surface remnants" to become high density- (HDL)-and apo AIV containing lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Intestinal apolipoprotein metabolism]. 208 69

In order to investigate the in vivo function of hepatic lipase, cats were injected with anti-cat hepatic lipase antibodies which produced a complete and specific inhibition of heparin-releasable hepatic lipase. The cat was chosen as an animal model because it displays, like man, a relative deficiency of lipoprotein lipase compared to hepatic lipase and because the possession of two subfractions of high density lipoproteins, HDL2 and HDL3. In fasted cats no changes were observed in plasma triglycerides or phospholipids. In fed animals triglycerides increased considerably, indicating that hepatic lipase may have a function in the postprandial phase. In fat-loaded cats (6 g of fat/kg) triglycerides in the d less than 1.019 g/ml fraction increased from 4 h after the blockade due to accumulation of lipoproteins with pre-beta-mobility containing the apoproteins, apo B-100, apo E and apo A-I. Apo B-48 did not accumulate consistently. Phospholipids in the HDL2-fraction and those in the HDL3-fraction of the fat-loaded cats tended to increase and decrease from 6 and 9 h after the blockade, respectively. The absolute change in HDL2 phospholipids approximated that of HDL3-phospholipids. Overall, the density of HDL particles decreased, apparently secondary to the accumulation of apo A-I in the d less than 1.019 g/ml fraction. Our findings suggest that hepatic lipase is involved in the hydrolysis of a special class of apo A-I containing triglyceride-rich lipoproteins synthesised in the postprandial phase.
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PMID:Studies on the function of hepatic lipase in the cat after immunological blockade of the enzyme in vivo. 312 48

Epidemiological, pathological and genetic studies show a strong positive correlation between elevated plasma concentrations of low-density lipoprotein (LDL) cholesterol and the risk of premature coronary heart disease. Apolipoprotein (apo) B-100 is the sole protein component of LDL and is the ligand responsible for the receptor-mediated uptake and clearance of LDL from the circulation. Apo B-100 is made by the liver and is essential for the assembly of triglyceride-rich very low-density lipoproteins (VLDL) in the cisternae of the endoplasmic reticulum and for their secretion into the plasma. VLDL transports triglyceride to peripheral muscle and adipose tissue, where the triglyceride is hydrolysed by lipoprotein lipase. The resultant particle, relatively enriched in cholesteryl ester, constitutes LDL. LDL delivers cholesterol to peripheral tissues where it is used for membrane and steroid hormone biosynthesis and to the liver, the only organ which can catabolize and excrete cholesterol. Plasma LDL levels are therefore determined by the balance between their rate of production from VLDL and clearance by the hepatic LDL (apo B/E) receptor pathway. Here we report the complete 4,563-amino-acid sequence of apo B-100 precursor (relative molecular mass (Mr) 514,000 (514K] determined from complementary DNA clones. Numerous lipid-binding structures are distributed throughout the extraordinary length of apo B-100 and must underlie its special functions as a nucleus for lipoprotein assembly and maintenance of plasma lipoprotein integrity. A domain enriched in basic amino-acid residues has been identified as important for the cellular uptake of cholesterol by the LDL receptor pathway.
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PMID:Complete protein sequence and identification of structural domains of human apolipoprotein B. 377 97

The rat liver secretes very low density lipoproteins (VLDL) containing either apoB-100 or apoB-48. After oral fat intake, chylomicrons containing apoB-48 and endogenously synthesized VLDL are mixed in the blood and the triglyceride clearance from these triglyceride-rich lipoprotein species compete for the same lipolytic pathway, i.e., lipoprotein lipase. A situation mimicking alimentary lipemia was induced by a short-term intravenous primed infusion of a chylomicron-like triglyceride emulsion to fed and fasted rats. The plasma concentration of apoB-100 and apoB-48 was monitored in triglyceride-rich lipoprotein subfractions after separation with density gradient ultracentrifugation by analytical SDS-PAGE. The net liver secretory output of VLDL was quantified by lipolytic blockade induced by Triton WR 1339. The chylomicron-like triglyceride emulsion induced a linear increase of large VLDL (Sf 60-400 subfraction containing both apoB-100 and apoB-48), almost to the same extent as that induced by Triton. The clearance of postprandial triglyceride-rich lipoproteins and both lipolysis and clearance of intravenously injected labeled rat chylomicrons was efficiently inhibited by the emulsion but not so complete as for fasting VLDL. The linearity of the VLDL increase and the very early response in the Intralipid-treated rats suggest that enhanced synthesis of VLDL is not a major cause for the accumulation. Rather, the present data indicate that a high plasma concentration of a chylomicron-like triglyceride emulsion competes efficiently with liver-derived VLDL for the same lipolytic pathway, which leads to accumulation in plasma of endogenous VLDL in the postprandial state.
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PMID:Endogenous triglyceride-rich lipoproteins accumulate in rat plasma when competing with a chylomicron-like triglyceride emulsion for a common lipolytic pathway. 759 79

1. Equine plasma contains lipoproteins corresponding to very low density (VLDL), low density (LDL) and high density lipoproteins (HDL). 2. HDL accounts for approximately 60% of plasma lipoprotein mass and consists of a single population of particles. 3. LDL is heterogeneous comprising three discrete subfractions. 4. Two proteins are found in the region of apolipoprotein (apo) B-100 in VLDL and LDL and a third similar to apoB-48 is in VLDL. 5. Lecithin:cholesterol acyl transferase is active in plasma and hepatic lipase and lipoprotein lipase are evident in post-heparin plasma. 6. There is no significant cholesteryl ester transfer protein activity.
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PMID:Plasma lipid transport in the horse (Equus caballus). 840 51


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