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)

Elevations in the mass of ether-linked diglycerides (i.e. 1-O-alk-1'-enyl-2-acyl-sn-glycerol (AAG) and 1-O-alkyl-2-acyl-sn-glycerol (Alkyl AG)) during cellular activation are prolonged in comparison to their 1,2-diacyl-sn-glycerol (DAG) counterparts. Since the metabolic removal of DAG is determined, in large part, by the rate of its phosphorylation by diglyceride kinase, we quantified differences in the activity of diglyceride kinase utilizing individual subclasses of diradyl glycerols as substrate. Rabbit brain microsomal diglyceride kinase activity was over 30-fold greater utilizing DAG as substrate (25.8 nmol.mg-1.min-1) in comparison to AAG (0.8 nmol.mg-1.min-1). No alterations in the affinity of microsomal diglyceride kinase for ATP were present (Km approximately 0.5 mM) utilizing each diradyl glycerol subclass. Similar subclass specificities for diglyceride kinase (i.e. DAG greater than Alkyl AG much greater than AAG) were present in brain and liver cytosol as well as in liver microsomes utilizing multiple assay conditions. In sharp contrast, Escherichia coli diglyceride kinase phosphorylated DAG, Alkyl AG, or AAG diradyl glycerol molecular subclasses at identical rates. Furthermore, although DAG was rapidly hydrolyzed by diglyceride lipase, catabolism of AAG or Alkyl AG by plasmalogenase, alkyl ether hydrolase, or diglyceride/monoglyceride lipase was undetectable. Collectively, these results demonstrate the importance of the differential catabolism of each diradyl glycerol molecular subclass as a primary determinant of their biologic half-lives. Since individual subclasses of diglycerides have distinct physical properties and physiologic functions, these results underscore the importance of lipid subclass specific metabolism in tailoring individual cellular responses during activation.
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PMID:Differential metabolism of diradyl glycerol molecular subclasses and molecular species by rabbit brain diglyceride kinase. 216 56

In the present study, we have characterized the properties of both diglyceride lipase (lipoprotein lipase, EC 3.1.1.24) and monoglyceride lipases (acylglycerol lipase, EC 3.1.1.23) in an attempt to assess the potential roles of these two enzymes in the release of arachidonate in activated human platelets. Diglyceride lipase exhibited maximal activity at pH 3.5, whereas monoglyceride lipase showed optimal activity at pH 7.0. Neither of the lipases were inhibited by EDTA or stimulated by Ca2+, Mg2+ or Mn2+. Both enzymes, however, were strongly inhibited by Hg2+ and Cu2+, indicating the involvement of sulfhydryl groups in catalytic activity. This suggestion was further supported by their sensitivity toward sulfhydryl inhibitors, with monoglyceride lipase being more susceptible to inhibition. Both lipases were found to be inhibited to a different degree by a variety of antiplatelet drugs blocking aggregation and arachidonate release. Kinetic studies indicated that dichotomous metabolism of diacylglycerol to monoacylglycerol and to phosphatidic acid could occur concurrently, since the apparent Km values for diglyceride lipase and for diglyceride kinase were comparable. Further studies showed that the specific activity of monoglyceride lipase was at least 100-fold higher than that of diglyceride lipase, indicating that the rate-limiting step in the release of arachidonate was the reaction catalyzed by diglyceride lipase.
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PMID:Monoglyceride and diglyceride lipases from human platelet microsomes. 314 16

Prostaglandins, thromboxanes, and leukotrienes have been implicated to play an important role in physiology as well as in a growing list of pathophysiologic conditions. These oxidation products of 8.11.14-eicosatrienoic-, 5.8.11.14.-eicosatetraenoic-, and 5.8.11.14.17.-pentaenoic acids have been collectively designated eicosanoids. Many clinically important diseases are associated with altered eicosanoid biosynthesis. Furthermore, a series of hormones are known to induce acutely formation of eicosanoids, suggesting a crucial role in a multitude of tissue responses including phenomena such as secretion, platelet aggregation, chemotaxis, and smooth muscle contraction. The major precursor for the eicosanoids seems to be 5.8.11.14.-eicosatetraenoic acid or arachidonic acid. Virtually all of arachidonic acid however is present in esterified form in complex glycerolipids. Since cyclooxygenase and the lipoxygenases utilize arachidonic acid in its free form, a set of acylhydrolases is required to liberate arachidonic acid from membrane lipids before eicosanoid formation can occur. It became only recently apparent that a minor acidic phospholipid, phosphatidylinositol, comprising only 5%-10% of the phospholipid mass in mammalian cells, plays an important role in arachidonic acid metabolism. Phosphatidylinositol--after phosphorylation to phosphatidylinositolphosphate and phosphatidylinositolbisphosphate--appears to be hydrolyzed by specific phospholipases C generating 1-stearoyl-2-arachidonoyl-diglyceride. Diglyceride serves as substrate for diglyceride lipase to form monoglyceride and free fatty acid. Alternatively diglyceride is phosphorylated by diglyceride kinase yielding phosphatidic acid, which is believed to be reincorporated into phosphatidylinositol. In addition to phosphatidylinositol phosphatidylcholine, phosphatidylethanolamine and phosphatidic acid may contribute to arachidonic acid release. These phospholipids are substrates for phospholipases A2 generating free arachidonic acid and the respective lysophospholipid. Understanding of the biochemistry of arachidonic acid liberation may be critical in developing strategies of pharmacological intervention in a variety of pathological conditions.
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PMID:[Eicosanoids and phospholipases]. 392 51

Human platelets incubated with thrombin and indomethacin (50 microgram/ml) exhibit an accumulation of diglyceride larger and more persistent than that observed for platelets incubated with thrombin alone. The accumulation appears to be due to the impaired metabolism of diglyceride by diglyceride lipase. In preparations of broken platelets, indomethacin leads to inhibition of diglyceride lipase. A similar inhibition can be achieved by the addition of soybean lipoxidase, and both inhibitions can be counteracted by reduced glutathione. Further, hydroperoxyeicosatetraenoic acid (100 microM) markedly depresses diglyceride lipase activity, whereas neither the hydroxy derivative nor eicosatetraenoic acid displays a comparable effect. Indomethacin at concentrations comparable to those impairing diglyceride lipase does not inhibit diglyceride kinase. This report constitutes the first evidence for the functioning of diglyceride lipase in normal stimulated platelets, and points to a possible role for fatty acid hydroperoxides in governing the activity of this enzyme.
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PMID:Indomethacin-induced accumulation of diglyceride in activated human platelets. The role of diglyceride lipase. 735 67

Endogenous phospholipid metabolism in stimulated human platelets was studied by phosphorus assay of major and minor components following separation by two-dimensional thin-layer chromatography. This procedure obviated the use of radioactive labels. Extensive changes were found in quantities of phosphatidylinositol (PI) and phosphatidic acid (PA) as a consequence of thrombin or collagen stimulation. Thrombin addition was followed by rapid alterations in the amount of endogenous PI and PA. The decrease in PI was not precisely reciprocated by an increase in PA when thrombin was the stimulus. This apparent discrepancy could be explained by removal of a transient intermediate in PI metabolism, such as diglyceride, formed by PI-specific phospholipase C (Rittenhouse-Simmons, S., J. Clin. Invest.63: 580-587, 1979). Diglyceride would be unavailable for PA formation by diglyceride kinase, if hydrolyzed by diglyceride lipase (Bell, R. L., D. A. Kennerly, N. Stanford, and P. W. Majerus. Proc. Natl. Acad. Sci. U. S. A.76: 3238-3241, 1979) to yield arachidonate for prostaglandin endoperoxide formation. Thrombin-treated platelets also accumulated lysophospho-glycerides. Specifically, lysophosphatidyl ethanolamines accumulated within 15s following thrombin addition. Fatty acid and aldehyde analysis indicated phospholipase A(2) activity, with an apparent preference for diacyl ethanolamine phosphoglycerides. In the case of collagen, these changes occurred concomitantly with aggregation and consumption of oxygen for prostaglandin endoperoxide formation.THESE STUDIES OF ENDOGENOUS PHOSPHOLIPID METABOLISM PROVIDE INFORMATION SUPPORTING THE EXISTENCE OF TWO PREVIOUSLY POSTULATED PATHWAYS FOR LIBERATION OF ARACHIDONIC ACID FROM PLATELET PHOSPHOLIPIDS: (a) the combined action of PI-specific phospholipase C plus diglyceride lipase yielding arachidonate derived from PI; and (b) a phospholipase A(2) acting primarily on diacyl ethanolamine phosphoglyceride.
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PMID:Phospholipid metabolism in stimulated human platelets. Changes in phosphatidylinositol, phosphatidic acid, and lysophospholipids. 740 Mar 15