Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.79 (hormone-sensitive lipase)
 2,163 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A triglyceride lipase was extracted from defatted pig adipose tissue powder with dilute ammonia and purified about 230-fold by a combination of ammonium sulfate fractionation, heparin-Sepharose 4B, DEAE-cellulose, and Sephadex G-150 column chromatographies and isoelectrofocusing electrophoresis. The enzyme was distinguishable in physical and kinetic properties from the two previously defined lipases in adipose tissue, lipoprotein lipase, and hormone-sensitive lipase. The purified enzyme was fully active in the absence of serum lipoprotein and was not stimulated by adenosine 3':5'-monophosphate-dependent protein kinase. In marked contrast to the already defined lipases, the enzyme was strongly inhibited by serum albumin. The enzyme had a molecular weigt of about 43,000, a pI of 5.2, and pH optimum of 7.0. The enzyme hydrolyzed triolein to oleic acid and glycerol, and did not exhibit esterase activity. The apparent Km for triolein was 0.05 mM. Physiological roles of this new species of lipase remained to be explored.
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PMID:Partial purification and characterization of a triglyceride lipase from pig adipose tissue. 1 Feb 95

Neutral cholesteryl ester hydrolase activity (EC 3.1.1.13) present in microsomes isolated from lactating rat mammary glands was found to be inhibited by a factor (or factors) occurring in the cytosolic fraction of male rat liver. The inhibitor was heat-labile, non-dialyzable, destroyed by proteolysis, and was stable following preparation of an acetone/diethyl ether powder of the cytosolic fraction. The protein also inhibited the activity of hormone-sensitive lipase (HSL) (from bovine adipose tissue) and esterase from Candida cylindracea, but seemed to be more active against the neutral hydrolase found in rat liver microsomes. For the mammary gland microsomal cholesteryl ester hydrolase, the extent of the inhibitory effect was dependent on the concentration of the cytosolic protein, 50% inhibition being achieved by about 100 micrograms of cytosolic protein, and on the method of initiating the enzyme assay. Kinetic analysis indicated that, under circumstances where the reaction was initiated by the addition of substrate, the inhibition was characterized as "uncompetitive." When an inhibitor/substrate complex was allowed to form in the absence of enzyme, an element of "competitive" inhibition was introduced into the reaction. Food withdrawal reduced the activity of the inhibitor in liver by 56%, but activity was fully restored by short-term re-feeding. In contrast, feeding a diet high in fat led to a 34% increase in activity. The present findings suggest that the inhibitory factor(s) may be involved in the regulation of the hydrolysis of cholesteryl esters in the liver and also in other cell types.
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PMID:Characterization of a cytosolic protein in rat liver inhibiting neutral cholesteryl ester hydrolase. 163 Feb 74

Long-chain fatty acid esters of 17 beta-estradiol and other steroid hormones, which are formed in hormone-sensitive tissues, can be regenerated to the free hormone by the action of an esterase present in the cytosol. This esterase has now been examined in bovine placenta cotyledons. Activity towards steroid fatty acid esters was accompanied by activity towards a diacylglycerol analogue and cholesteryl oleate. During purification procedures, the ratio of activities towards the diacylglycerol analogue and estradiol 17 beta-oleate remained approximately constant. Activity towards these two substrates was inhibited by increasing concentrations of HgCl2 and phenylmethanesulfonyl fluoride in a parallel manner. Upon treatment with [3H]diisopropyl fluorophosphate, a major labelled species of Mr approx. 84,000 was formed. Activation by ATP and the catalytic subunit of cAMP-dependent protein kinase occurred. These properties were very similar to those of the hormone-sensitive lipase of bovine adipose tissue previously reported and run in parallel in this study. A highly purified preparation of this latter enzyme was found to hydrolyse steroid fatty acid esters and relative activities towards such substrates, diacylglycerol analogue and cholesteryl oleate, were similar to the placenta esterase. When the two esterases were phosphorylated with [gamma-32P]ATP, a labelled species of Mr 84,000 was isolated in both cases by use of an antibody raised against purified hormone-sensitive lipase of bovine adipose tissue. It is concluded that hormone-sensitive lipase is very likely the enzyme responsible for hydrolysis of steroid fatty acid esters in bovine placenta and possibly steroid hormone target tissues in general.
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PMID:Hormone-sensitive lipase is involved in the hydrolysis of lipoidal derivatives of estrogens and other steroid hormones. 319 30

Rat adipose tissue was homogenized in 0.154 m KCl, and the supernatant fluid, obtained after centrifugation at 15,000 g, was extracted with benzene to remove triglycerides. Most of the lipase activity in the extracted fluid was precipitated with ammonium sulfate between 15 and 40% saturation. The specific activity of the lipase in this fraction was about three times that in the benzene-extracted supernatant fluid. The specific activity of the monoglyceride esterase was increased to a lesser extent. Lipase activity in the benzene-extracted fluid and in the ammonium sulfate fraction was increased 15-45% by incubation with 0.3 mm ATP, 10 mm MgCl(2), and 0.03 mm cyclic AMP for 10 min before assay. None of these compounds alone or in combinations of two was as effective as all three together. The specific activity of the 15-40% ammonium sulfate fraction prepared from fat cells exposed to epinephrine and glucagon was greater than that from portions of the same cell pool not exposed to hormones. In addition, the already elevated lipase activity in preparations from hormone-treated cells was not enhanced by incubation with ATP, MgCl(2), and cyclic AMP. Thus, it seems probable that the lipase activity in the ammonium sulfate fractions represents, at least in part, hormone-sensitive lipase.
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PMID:Activation of hormone-sensitive lipase in extracts of adipose tissue. 432 64

Steroidogenic cells store cholesteryl esters, precursors for steroid hormone synthesis, in intracellular lipid droplets. Cholesteryl ester hydrolysis is activated by protein kinase A and catalyzed by cholesteryl esterase. The esterase is similar, if not identical, to hormone-sensitive lipase in adipocytes where an analogous lipolytic mechanism occurs. Perilipins, proteins located exclusively at lipid droplet surfaces in adipocytes, are polyphosphorylated by protein kinase A in response to lipolytic stimuli, suggesting a role for these proteins in mediating lipid metabolism. The present study reveals that perilipins are associated with cholesteryl ester droplets in two steroidogenic cell lines: Y-1 adrenal cortical cells and MA-10 Leydig cells. The relative abundance of perilipin mRNAs and protein is much less in steroidogenic cells than in adipocytes. Like adipocytes, steroidogenic cells express perilipin A; additionally, the latter cells contain relatively abundant amounts of perilipin C, a protein that is not detectable in adipocytes by Western analysis. The data suggest a strong link between perilipins and lipid hydrolysis that is mediated by the hormone-sensitive lipase/cholesteryl esterase class of enzymes.
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PMID:Perilipins are associated with cholesteryl ester droplets in steroidogenic adrenal cortical and Leydig cells. 762 16

Microsomal arylacetamide deacetylase (DAC) competes against the activity of cytosolic arylamine N-acetyltransferase, which catalyzes one of the initial biotransformation pathways for arylamine and heterocyclic amine carcinogens in many species and tissues. Activity determination and immunoblot analysis of DAC in human target tissues for arylamine carcinogens revealed that in extrahepatic tissues, additional enzymes are responsible for any deacetylation activity, whereas a single enzyme predominantly catalyzes this hydrolytic reaction in liver. We isolated and characterized a full-length cDNA from a human liver lambda gt11 library. This clone encodes an open reading frame of 400 amino acids with a deduced molecular mass of 45.7 kDa and contains two putative glycosylation sites. The 3'-untranslated region contains two putative polyadenylation signals. The cDNA was confirmed to be that for DAC in tryptic peptides from the purified human liver protein. Highest sequence similarity of DAC was found in a series of prokaryotic esterases encompassing the putative active site. Two extended regions of significant sequence homology with hormone-sensitive lipase and with lipase 2 from Moraxella TA144 were identified, whereas similarity to carboxyl esterases was restricted to the region encompassing the putative active site, indicating that DAC should be classified as esterase. This cDNA provides an important tool to study deacetylation and its effects on the metabolic activation of arylamine and heterocyclic amine carcinogens.
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PMID:Human liver arylacetamide deacetylase. Molecular cloning of a novel esterase involved in the metabolic activation of arylamine carcinogens with high sequence similarity to hormone-sensitive lipase. 806 7

The consensus pentapeptide GXSXG is found in virtually all lipases/esterases and generally contains the active site serine. The primary sequence of hormone-sensitive lipase contains a single copy of this pentapeptide, surrounding Ser-423. We have analyzed the catalytic role of Ser-423 by site-directed mutagenesis and expression of the mutant hormone-sensitive lipase in COS cells. Substitution of Ser-423 by several different amino acids resulted in the complete abolition of both lipase and esterase activity, whereas mutation of other conserved serine residues had no effect on the catalytic activity. These results strongly suggest that Ser-423 is the active site serine of hormone-sensitive lipase.
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PMID:Identification of the active site serine of hormone-sensitive lipase by site-directed mutagenesis. 818 91

It is expected that hormone-sensitive lipase (HSL), like most other lipases and esterases, adopts an alpha/beta-hydrolase fold and has a catalytic triad of serine, aspartic or glutamic acid, and histidine. Recently, we have published a three-dimensional model for the C-terminal catalytic domain of HSL, having an alpha/beta-hydrolase fold and with Ser-423(1), Asp-703 and His-733 in the catalytic triad (Contreras et al. (1996) J. Biol. Chem. 271, 31426-31430). It has been shown that Ser-423, situated in the motif GXSXG, is essential for catalysis (Holm et al. (1994) FEBS Lett. 344, 234-238). The suggested aspartic acid and histidine were here probed by site-directed mutagenesis. Mutants of residues Asp-703 and His-733 are devoid of both lipase and esterase activity, which is not the case for mutants of other tested aspartic acid and histidine residues. Thus, the presented data support the three-dimensional model structure with Asp-703 and His-733 as part of the traid.
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PMID:Identification of essential aspartic acid and histidine residues of hormone-sensitive lipase: apparent residues of the catalytic triad. 909 13

An esterase from Escherichia coli that is a member of the hormone-sensitive lipase (HSL) family was overproduced, purified and characterized. It is encoded by the ybaC gene and composed of 319 amino acid residues with an Mr of 36038. The enzymic activity was determined by using various p-nitrophenyl esters of fatty acids as a substrate at 25 degreesC and pH 7.1. The enzyme showed hydrolytic activity towards substrates with an acyl chain length of less than 8, whereas it showed little hydrolytic activity towards those with an acyl chain length of more than 10. In addition, it showed little hydrolytic activity towards trioleoylglycerol and cholesterol oleate. Determination of the kinetic parameters for the hydrolyses of the substrates from C2 to C8 indicates that C4 and C5 substrates are the most preferred. Close agreement between the Mr determined by SDS/PAGE (37000) and column chromatography (38000) suggests that the enzyme exists in a monomeric form. It is an acidic protein with a pI value of 4.1. The far-UV CD spectrum suggests that its helical content is 26.1%. Comparison of the amino acid sequence of this enzyme with those involved in the HSL family allows us to propose that Ser165, Asp262 and His292 constitute the catalytic triad of E. coli esterase.
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PMID:An esterase from Escherichia coli with a sequence similarity to hormone-sensitive lipase. 957 53

We previously purified a new esterase from the thermoacidophilic eubacterium Bacillus acidocaldarius whose N-terminal sequence corresponds to an open reading frame (ORF3) reported to show homology with the mammalian hormone-sensitive lipase (HSL)-like group of the esterase/lipase family. To compare the biochemical properties of this thermophilic enzyme with those of the homologous mesophilic and psychrophilic members of the HSL group, an overexpression system in Escherichia coli was established. The protein, expressed in soluble and active form at 10 mg/l E. coli culture, was purified to homogeneity and characterized biochemically. The enzyme, a 34 kDa monomeric protein, was demonstrated to be a B'-type carboxylesterase (EC 3.1.1.1) on the basis of substrate specificity and the action of inhibitors. Among the p-nitrophenyl (PNP) esters tested the best substrate was PNP-exanoate with Km and kcat values of 11+/-2 microM (mean+/-S.D., n=3) and 6610+/-880 s-1 (mean+/-S.D., n=3) respectively at 70 degreesC and pH7.1. In spite of relatively high sequence identity with the mammalian HSLs, the psychrophilic Moraxella TA144 lipase 2 and the human liver arylacetamide deacetylase, no lipase or amidase activity was detected. A series of substrates were tested for enantioselectivity. Substantial enantioselectivity was observed only in the resolution of (+/-)-3-bromo-5-(hydroxymethyl)-Delta2-isoxazoline, where the (R)-product was obtained with an 84% enantiomeric excess at 36% conversion. The enzyme was also able to synthesize acetyl esters when tested in vinyl acetate and toluene. Inactivation by diethylpyrocarbonate, diethyl-p-nitrophenyl phosphate, di-isopropylphosphofluoridate (DFP) and physostigmine, as well as labelling with [3H]DFP, supported our previous suggestion of a catalytic triad made up of Ser-His-Asp. The activity-stability-temperature relationship is discussed in relation to those of the homologous members of the HSL group.
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PMID:Overexpression and properties of a new thermophilic and thermostable esterase from Bacillus acidocaldarius with sequence similarity to hormone-sensitive lipase subfamily. 957 69


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