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)

A lower accessibility to water-soluble quenchers of tryptophanyls of VLDL apolipoproteins B, E, C as compared to LDL apoB chromophores has been detected by a fluorescence quenching technique. The dynamic behaviour of the tryptophanyls of VLDL amphipathic apolipoproteins E and C did not change in the presence of a detergent, Tween-20, at sub-lytic concentrations. However, a reversible structural transition registered by the 'red' shift of the emission spectrum maximum and the changes in the quenching pattern by I- occurred under these conditions. The increase in the VLDL tryptophanyl accessibility to acrylamide and the decrease in the quenching constant were observed at partial and complete solubilization of the VLDL particles by the detergent. Dissociation of apolipoproteins from VLDL occurred after their treatment with Tween-20 or lipoprotein lipase isolated from bovine milk, and the tryptophanyl population not participating in fluorescence energy transfer on lipid phase-localized fluorescent probe pyrene appeared. In the presence of Tween-20, the relative affinity of apoE for the lipid matrix of VLDL was lower than that of apoC. Besides, the uncompetitive mode of inhibition of the LPL activity by apoC-III has been demonstrated. It is suggested that: (1) the amphipathic apolipoproteins E and C are organized as clusters on the VLDL surface and/or partially shielded by apolipoprotein B: (2) self-regulation of lypolysis may exist involving detergent-like reaction product accumulation and changes in relative apolipoprotein contents.
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PMID:Topo-dynamic characteristics of human plasma VLDL apolipoproteins and efficiency of triacylglycerol hydrolysis by lipoprotein lipase. 277 63

The low-density-lipoprotein (LDL) receptor is a cell-surface protein that plays an important part in the metabolism of cholesterol by mediating the uptake of LDL from plasma into cells. Although LDL particles bind to the LDL receptor through their apolipoprotein B (apo B) and apolipoprotein E (apo E) moieties, other apo E-containing particles, like chylomicron remnants, are not dependent on the LDL receptor for uptake into cells. Chylomicrons formed in the intestinal mucosa during the absorption of the products of digestion, are processed by the peripheral circulation by lipoprotein lipase, which catalyses the breakdown of triglycerides in chylomicrons to free fatty acids and glycerol. The resulting chylomicron remnants, which are cholesterol-rich lipoproteins, are subsequently taken up in the liver. A second distinct protein that binds to apo E-containing lipoproteins, but not to LDL, has been proposed to be the receptor mediating the clearance of chylomicron remnants from the plasma. This protein has a relative molecular mass (Mr) of 56,000 (56K). More recent studies have failed, however, to establish whether this protein is a cell-surface receptor. Here we describe crosslinking experiments in which apo E liposomes were found to bind specifically to the cell surface of hepG2 cells and to human liver membranes. The size and immunological cross-reactivity of the protein to which the liposomes bound was indistinguishable from that of the recently cloned and sequenced LDL-receptor-related protein, LRP. We therefore conclude that the LRP might function as an apo E receptor.
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PMID:The LDL-receptor-related protein, LRP, is an apolipoprotein E-binding protein. 277 54

Effects on plasma lipoproteins, lecithin:cholesterol acyltransferase (LCAT), and postheparin lipase (LPL and HTGL) activities were studied in 18 patients with familial hypercholesterolemia during 8-week treatment periods with colestipol (15 g/d), fenofibrate (0.25 g/d), and colestipol plus fenofibrate. Lipoprotein lipids and apolipoproteins were determined by standard procedures, LCAT by a self-substrate method, and lipases by nonradioisotopic methods. Colestipol and fenofibrate, each given independently, caused similar percentage decreases in LDL cholesterol and apolipoprotein B: -18.4% and -8.6% v -17.4% and -10.6% Colestipol increased the VLDL cholesterol concentration, whereas fenofibrate reduced this parameter but increased HDL cholesterol and apolipoprotein A-I levels. The combination of both drugs led to a substantial fall in LDL cholesterol (-36.8%) and in apolipoprotein B (-28.3%) and maintained the other effects of fenofibrate on VLDL and HDL. Colestipol, given independently or with fenofibrate, produced an increase of the fractional esterification rate of the LCAT enzyme (+25.3% and +36.2%). Fenofibrate stimulated the postheparin LPL enzyme by +16.1% and +21.7%, respectively. This study indicates the complementarity in effectiveness when both drugs were administered together. The appropriate reduction in LDL was combined with the favorable effects on HDL in familial hypercholesterolemia.
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PMID:Low-dose colestipol plus fenofibrate: effects on plasma lipoproteins, lecithin:cholesterol acyltransferase, and postheparin lipases in familial hypercholesterolemia. 291 46

The human plasma lipoproteins encompass a broad spectrum of particles of widely varying physical and chemical properties whose metabolism is directed by their protein components. Apolipoprotein B100 (apo B100) is the major structural protein resident in particles within the Svedberg flotation range 0-400. The largest of these, the very low density lipoprotein (VLDL), rich in triglyceride, are metabolised by sequential delipidation through a transient intermediate density lipoprotein (IDL) to cholesterol-rich low density lipoproteins (LDL). Several components contribute to the regulation of this process, including (a) the lipolytic enzymes lipoprotein lipase and hepatic lipase (b), apolipoproteins B, CII, CIII and E, and (c) the apolipoprotein B/E or LDL receptor. Lipoprotein lipase acts primarily on large VLDL of Sf 60-400. Hepatic lipase on the other hand seems to be critical for the conversion of smaller particles (Sf 12-60) to LDL (Sf 0-12). Although most apo B100 flux is directed to the production of the delipidation end product LDL, along the length of the cascade there is potential for direct removal of particles from the system, probably via the actions of cell membrane receptors. This alternative pathway is particularly evident in hypertriglyceridaemic subjects, in whom the delipidation process is retarded. VLDL metabolism shows inter subject variability even in normal individuals. In this regard, apolipoprotein E plays an important role. Normolipidaemic individuals homozygous for the apo E2 variant exhibit gross disturbances in the transit of B protein through the VLDL-IDL-LDL chain.
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PMID:Very low density lipoprotein apolipoprotein B metabolism in humans. 305 Feb 67

Although the direct conversion of very low density lipoproteins (VLDL) into low density (LDL) and high density (HDL) lipoproteins only requires lipoprotein lipase (LPL) as a catalyst and albumin as the fatty acid acceptor, the in vitro-formed LDL and HDL differ chemically from their native counterparts. To investigate the reason(s) for these differences, VLDL were treated with human milk LPL in the presence of albumin, and the LPL-generated LDL1-, LDL2-, and HDL-like particles were characterized by lipid and apolipoprotein composition. Results showed that the removal of apolipoproteins B, C, and E from VLDL was proportional to the degree of triglyceride hydrolysis with LDL2 particles as the major and LDL1 and HDL + VHDL particles as the minor products of a complete in vitro lipolysis of VLDL. In comparison with native counterparts, the in vitro-formed LDL2 and HDL + VHDL were characterized by lower levels of triglyceride and cholesterol ester and higher levels of free cholesterol and lipid phosphorus. The characterization of lipoprotein particles present in the in vitro-produced LDL2 showed that, as in plasma LDL2, lipoprotein B (LP-B) was the major apolipoprotein B-containing lipoprotein accounting for over 90% of the total apolipoprotein B. Other, minor species of apolipoprotein B-containing lipoproteins included LP-B:C-I:E and LP-B:C-I:C-II:C-III. The lipid composition of in vitro-formed LP-B closely resembled that of plasma LP-B. The major parts of apolipoproteins C and E present in VLDL were released to HDL + VHDL as simple, cholesterol/phospholipid-rich lipoproteins including LP-C-I, LP-C-II, LP-C-III, and LP-E. However, some of these same simple lipoprotein particles were present after ultracentrifugation in the LDL2 density segment because of their hydrated density and/or because they formed, in the absence of naturally occurring acceptors (LP-A-I:A-II), weak associations with LP-B. Thus, the presence of varying amounts of these cholesterol/phospholipid-rich lipoproteins in the in vitro-formed LDL2 appears to be the main reason for their compositional difference from native LDL2. These results demonstrate that the formation of LP-B as the major apolipoprotein B-containing product of VLDL lipolysis only requires LPL as a catalyst and albumin as the fatty acid acceptor. However, under physiological circumstances, other modulating agents are necessary to prevent the accumulation and interaction of phospholipid/cholesterol-rich apolipoprotein C- and E-containing particles.
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PMID:Lipolytic degradation of human very low density lipoproteins by human milk lipoprotein lipase: the identification of lipoprotein B as the main lipoprotein degradation product. 308 Sep 47

Serum lipid and lipoprotein levels, apolipoproteins A-I and B, and lipolytic enzyme activities were studied in 14 young male cyclists and in 21 age-matched sedentary controls. While there were no significant differences in serum cholesterol between the two groups, the cyclists showed a significant decrease in serum triglycerides (P less than 0.05) and LDL cholesterol (P less than 0.05) and had significantly higher levels of HDL cholesterol (P less than 0.01) and HDL2 cholesterol (P less than 0.001). Significantly lower serum cholesterol/HDL cholesterol (P less than 0.001) and LDL cholesterol/HDL cholesterol (P less than 0.001) ratios and a significantly higher HDL2 cholesterol/HDL3 cholesterol ratio (P less than 0.001) were observed in the athletes. Serum apolipoprotein B was lower and the Apo B/Apo A-I ratio significantly reduced in the athletes. No significant differences emerged between the two groups in plasma post-heparin lipoprotein lipase activity (LPL) and in hepatic triglyceride lipase activity (HTGL), and there were no correlations between HDL cholesterol and lipolytic enzyme activities. In conclusion, this cross-sectional study may indicate that an aerobic training program such as cycling is associated with an advantageous lipoprotein pattern; some factors other than lipolytic activity may contribute to increase the HDL cholesterol levels in physical training.
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PMID:Heparin-released plasma lipase activities, lipoprotein and apoprotein levels in young adult cyclists and sedentary men. 314 6

Vitellogenin, an ancient animal protein, is the major yolk protein of eggs, where it is used as a food source during embryogenesis. Here it is shown that vitellogenins, including those from the invertebrates Caenorhabditis elegans and Drosophila melanogaster, contain domains that are homologous with parts of apolipoprotein B-100 (apoB-100) of human low-density lipoprotein and human lipoprotein lipase. As vitellogenins are likely to have been used by invertebrates during embryogenesis well before the circulation of lipids appeared in vertebrates, it is suggested that copies of a precursor gene, serving a function similar to vitellogenin, were modified to code for part of apoB-100 and lipoprotein lipase in vertebrates. In addition to providing a link between invertebrates and vertebrates for proteins involved in lipid transport, these homologies suggest new functions for vitellogenin other than being a yolk food for the developing embryo.
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PMID:Is vitellogenin an ancestor of apolipoprotein B-100 of human low-density lipoprotein and human lipoprotein lipase? 314 37

Incubation of low density lipoprotein(s) (LDL) with either lipoprotein lipase or hepatic lipase led to modification of the core lipid composition of LDL. Both lipases modified LDL by substantially reducing core triglyceride content without producing marked differences in size, charge, or lipid peroxide content in comparison to native LDL. The triglyceride-depleted forms of LDL that result from treatment with these two enzymes were degraded at approximately twice the rate of native LDL by human monocyte-derived macrophages (HMDM). Lipase-modified LDL degradation was inhibited by chloroquine, suggesting lysosomal involvement in LDL cellular processing. The increased degradation by macrophages of the LDL modified by these lipases was accompanied by enhanced cholesterol esterification rates, as well as by an increase in cellular free and esterified cholesterol content. In a patient with hepatic triglyceride lipase deficiency, degradation of the triglyceride-rich LDL by HMDM was approximately half that of normal LDL. Following in vitro incubation of LDL from this patient with either lipoprotein or hepatic lipase, lipoprotein degradation increased to normal. Several lines of evidence indicate that LDL modified by both lipases were taken up by the LDL receptor and not by the scavenger receptor. 1) The degradation of lipase-modified LDL in nonphagocytic cells (human skin fibroblast and arterial smooth muscle cells) as well as in phagocytic cells (HMDM, J-774, HL-60, and U-937 cell lines) could be dissociated from that of acetylated LDL and was always higher than that of native LDL. A similar pattern was found for cellular cholesterol esterification and cholesterol mass. 2) LDL receptor-negative fibroblasts did not degrade lipase-modified LDL. 3) A monoclonal antibody to the LDL receptor inhibited macrophage degradation of the lipase-modified LDL. 4) Excess amounts of unlabeled LDL competed substantially with 125I-labeled lipase-modified LDL for degradation by both macrophages and fibroblasts. Thus, lipase-modified LDL can cause significant cholesterol accumulation in macrophages even though it is taken up by LDL and not by the scavenger receptor. This effect could possibly be related to the reduced triglyceride content in the core of LDL, which may alter presentation of the LDL receptor-binding domain of apolipoprotein B on the particle surface, thereby leading to increased recognition and cellular uptake via the LDL receptor pathway.
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PMID:Modification of low density lipoprotein by lipoprotein lipase or hepatic lipase induces enhanced uptake and cholesterol accumulation in cells. 317 May 89

Cardiovascular complications are a well recognized side-effect of antihormonal therapy in men with prostatic carcinoma. We studied changes in plasma lipoproteins in patients with prostate cancer during treatment with several androgen suppression therapies. Estrogen, orchiectomy, and a combination of LHRH agonist and antiandrogen (flutamide) reduced plasma testosterone concentrations (89-92%) and plasma estradiol decreased by 85%, 44%, and 54%, respectively. Estrogen induced hypertriglyceridemia and elevation of plasma HDL cholesterol, phospholipid, and apolipoprotein A-I and A-II concentrations. Low density lipoprotein (LDL) cholesterol decreased but LDL apolipoprotein B did not. These results suggest that the cardiovascular complications that occur during estrogen administration are not mediated through changes in lipoprotein profile, other than the hypertriglyceridemic effect. Orchiectomy caused hypercholesterolemia and an increase in both total and LDL apolipoprotein B, all of which are strong determinants of cardiovascular disease. The high density lipoprotein (HDL) concentration was not affected despite a reduction in plasma testosterone, perhaps due to a simultaneous decrease in estradiol. Combination therapy had no effect on plasma lipid and apolipoprotein B concentrations, but very low density lipoprotein (VLDL) apolipoprotein B decreased, and LDL apolipoprotein B increased. The HDL cholesterol and apolipoprotein A-I concentrations increased but A-II and phospholipids did not. These results suggest enhanced lipoprotein lipase activity, consistent with the reciprocal changes in VLDL and LDL apolipoprotein B levels, apolipoprotein B enrichment of LDL particles, and increase in HDL cholesterol. The higher apolipoprotein A-I to A-II ratio indicates an increase in HDL2 subfraction due to inhibition of endothelial hepatic lipase, increased secretion of apolipoprotein A-I, or both. These effects are attributed to estradiol, which decreased less than after orchiectomy, and to additional adrenal androgen inhibition by flutamide. We conclude that estradiol plays an important role in determining plasma lipoprotein concentrations in men, and androgens exert an antagonist effect. The lipoprotein profile resulting from the combination treatment is more beneficial than that resulting from orchiectomy or estrogen administration.
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PMID:Changes in plasma lipoproteins during various androgen suppression therapies in men with prostatic carcinoma: effects of orchiectomy, estrogen, and combination treatment with luteinizing hormone-releasing hormone agonist and flutamide. 327 21

To clarify the role of lipoprotein lipase (LPL) in the catabolism of nascent and circulating very low density lipoproteins (VLDL) and in the conversion of VLDL to low density lipoproteins (LDL), studies were performed in which LPL activity was inhibited in the cynomolgus monkey by intravenous infusion of inhibitory polyclonal or monoclonal antibodies. Inhibition of LPL activity resulted in a three- to fivefold increase in plasma triglyceride levels within 3 h. Analytical ultracentrifugation and gradient gel electrophoresis demonstrated an increase predominantly in more buoyant, larger VLDL (Sf 400-60). LDL and high density lipoprotein (HDL) cholesterol levels fell during this same time period, whereas triglyceride in LDL and HDL increased. Kinetic studies, utilizing radiolabeled human VLDL, demonstrated that LPL inhibition resulted in a marked decrease in the catabolism of large (Sf 400-100) VLDL apolipoprotein B (apoB). The catabolism of more dense VLDL (Sf 60-20) was also inhibited, although to a lesser extent. However, there was a complete block in the conversion of tracer in both Sf 400-100 and 60-20 VLDL apoB into LDL during LPL inhibition. Similarly, endogenous labeling of VLDL using [3H]leucine demonstrated that in the absence of LPL, no radiolabeled apoB appeared in LDL. We conclude that although catabolism of dense VLDL continues in the absence of LPL, this enzyme is required for the generation of LDL.
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PMID:Lipoprotein metabolism during acute inhibition of lipoprotein lipase in the cynomolgus monkey. 327 35


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