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)

Two major isoforms of the bovine analogue to human apolipoprotein (apo) CII were purified from plasma. They were both as effective as human apo CII in activating lipoprotein lipase. Amino acid sequencing revealed that one form contained 79 amino acid residues, and corresponded to human pro apo CII. The other form lacked the first six residues at its N-terminus. This was apparently due to cleavage of the -Gln-Asp- linkage in the sequence H2N-Ala-His-Val-Pro-Gln-Gln-Asp-Glu-, analogous to cleavages described for human apo AI and apo CII. Previous studies with human apo CII have shown that the ability to activate lipoprotein lipase resides in the C-terminal third of the molecule. This was highly conserved in the bovine analogue: of the 30 last residues, 21 are identical. Five residues in this part of human apo CII have been reported to be essential for activation of lipoprotein lipase. Only one of these, Tyr63, is present in the bovine sequence. The bovine structure contains a threonine at position 61, instead of serine in the human, and the four last residues are -Ser-Gly-Lys-Asp instead of the allegedly necessary -Lys-Gly-Glu-Glu. Three differently sialylated isoforms of the bovine analogue to human apolipoprotein CIII were also isolated and partially sequenced. All three lacked the first three N-terminal residues as compared to sequences from other species (man, dog and rat). Sequence differences were more pronounced at the ends than in the central parts of the apo CIII molecules.
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PMID:Primary structure of the bovine analogues to human apolipoproteins CII and CIII. Studies on isoforms and evidence for proteolytic processing. 220 8

In this study we have prepared peptides of the C-terminal domain of apolipoprotein CII (ApoCII) by a solid-peptide-synthesis technique and demonstrated that the C-terminal tetrapeptide, Lys-Gly-Glu-Glu, represents an inhibitor of lipoprotein lipase. The tetrapeptide not only inhibits the basal activity of lipoprotein lipase, but also blocks the activation effect of native ApoCII. The lengthening of this tetrapeptide resulted in a corresponding increase in affinity for lipoprotein lipase. This suggested that amino acids other than those of the C-terminal tetrapeptide also contribute to the binding affinity of ApoCII for lipoprotein lipase. On the basis of an essential requirement of the ApoCII terminal domain for binding to lipoprotein lipase, we suggest that the initial interaction of ApoCII, mediated via the C-terminal tetrapeptide, promotes the proper alignment of ApoCII with lipoprotein lipase, followed by the weak interaction of the ApoCII activator domain with the lipoprotein lipase activator site, enhancing the lipolysis process.
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PMID:C-terminal domain of apolipoprotein CII as both activator and competitive inhibitor of lipoprotein lipase. 238 83

Identification of three overlapping clones in a canine genomic lambda phage library allowed us to determine a detailed restriction enzyme map of the primary transcriptional unit of the pancreatic lipase gene (15.5 kilobase pairs) as well as 15 and 6 kilobase pairs of 5'- and 3'-flanking regions, respectively. DNA sequence analysis provided the primary structure of (a) 1,345 nucleotides (nt) of 5'-flanking sequence including CAAT and TATA boxes at positions -112 and -35, respectively, and a class 2 glucocorticoid receptor binding sequence at position -97, (b) 13,127 out of approximately 15,500 nt of the transcriptional unit which is organized into 13 exon sequences, and (c) 1,270 nt of 3'-flanking sequence. Exon 1 encodes the entire 5'-nontranslated mRNA sequence; exon 2, the ATG initiation codon and the hydrophobic portion of the signal peptide; and exon 6, Ser154 which shows homology to the active Ser152 in the porcine enzyme. Comparison of the amino acid sequences of human lipoprotein lipase, rat hepatic lipase, and Drosophila yolk proteins 1, 2, and 3 with canine pancreatic lipase shows that the central region of highest homology (encoded by exons 6-8 in the dog gene) contains four highly conserved subregions which may play a critical role in enzyme-substrate and protein-ligand binding for lipases and yolk proteins, respectively. Comparison of the sequences of 10 lipases from prokaryotes and eukaryotes identifies a 9-residue consensus sequence surrounding the active serine which includes the previously identified sequence Gly-X-Ser-X-Gly. The hydrophobic nature of this sequence in the 10 lipases contrasts with the hydrophilic nature of the corresponding sequences in serine proteases and thus defines an active site serine consensus sequence specific for lipases. An analysis of 5'- and 3'-flanking and intron 1-4 sequences in transient expression studies with AR4-2J and 266-6 cells was unable to reveal tissue-specific promoter or enhancer sequences.
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PMID:Structure of the canine pancreatic lipase gene. 250 43

The primary structure of bovine milk lipoprotein lipase (bLPL) was determined by alignment of peptides produced by tryptic digestion, Staphylococcus aureus V8 protease digestion, and cyanogen bromide cleavage. bLPL consists of 450 amino acid residues. Most tryptic peptides were isolated and analyzed, except for the dipeptide, Glu-Lys (position 423-424), and the 2 Lys at positions 416 and 488. Peptides resulting from digestion by S. aureus V8 protease and cyanogen bromide cleavage filled the missing part and completed the primary sequence of bLPL. The NH2 terminus of bLPL was determined to be Asp by sequencing the intact protein with a gas phase sequencer for up to 30 residues, whereas the COOH terminus was identified as Gly through, carboxyl peptidase Y cleavage. The enzyme contains 10 cysteine residues, all of which exist in disulfide linkages. They are formed between Cys29 and Cys42, Cys218 and Cys241, Cys266 and Cys285, Cys277, and Cys280, and Cys420 and Cys440. The sites of N-glycosylation were identified at Asn44 and Asn361. In accordance with a common structural homology of serine-type esterases, -G-X-S-X-G- (Yang, C. Y., Manoogian, D., Pao, Q., Lee, F., Knapp, R. D., Gotto, A. M., Jr., and Pownall, H. J. (1987) J. Biol. Chem., 262, 3086-3191), the active site serine of bLPL was assigned to the serine at position 134. The chymotrypsin nick of bLPL was determined to be between residues 390 and 391. A model of the enzyme is proposed on the basis of our data and available chemical data.
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PMID:Structure of bovine milk lipoprotein lipase. 267 42

Bovine milk lipoprotein lipase was subjected to amino acid sequence analysis. The first 19 amino-terminal residues were Asp-Arg-Ile-Thr-Gly-Gly-Lys-Asp-Phe-Arg-Asp-Ile-Glu-Ser-Lys-Phe-Ala-Leu- Arg. In addition, reversed-phase high-performance liquid chromatography of a tryptic digest of reduced and alkylated lipase resolved a number of peptides, five of which contained cysteine. Sequence analysis of the tryptic peptides revealed in most instances a close homology to porcine pancreatic lipase. Based on this homology, the relative alignment of the sequenced lipoprotein lipase peptides can be made. In addition, a potential binding site for the triacylglycerol substrate and a carbohydrate-binding domain for lipoprotein lipase are postulated.
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PMID:Homology of lipoprotein lipase to pancreatic lipase. 345 70

Lipoprotein lipase from bovine milk reacted stoichiometrically with diisopropylphosphorofluoridate (DFP), an inactivator of serine esterases, resulting in the loss of enzymatic activity against triacylglycerols. The reaction obeyed first-order kinetics with a rate constant of 0.69 h-1. In order to isolate the peptide containing the diisopropylphosphoryl moiety (DIP), partially purified lipoprotein lipase was covalently labeled with [3H]DFP, and the labeled protein was reduced, carboxymethylated, and further purified to about 90% homogeneity. Cyanogen bromide cleavage followed by gel filtration yielded a radioactive peptide of 6-8 kDa. This peptide was succinylated and then digested with Staphylococcus aureus V8 proteinase. From this digest, a peptide containing 0.95 mol of [3H] DIP/mol of peptide was isolated by gel-permeation chromatography followed by reverse-phase high performance liquid chromatography. Automated Edman degradation provided the following sequence: Ala-Ile-Gly-Ile-His-Trp-Gly-Gly- (DIP)Ser-Pro-Asn-Gln-Lys-Asn-Gly-Ala-Val-Phe-Ile-Asn-(Ser, Leu)-Glu. Analysis of the sequence for secondary structure suggests that the reactive serine of lipoprotein lipase is in a beta-turn, a structure similar to those of the active sites of most other serine proteinases. Lipoprotein lipase appears to share this secondary structure with other serine hydrolases despite significant differences in the primary structure of this domain.
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PMID:Isolation of an active-site peptide of lipoprotein lipase from bovine milk and determination of its amino acid sequence. 352 32

The effects of chronic ethanol consumption on lactational performance were studied in the rat on day 15 after delivery by determining mammary gland and milk composition, while growth rate and metabolic parameters were studied in pups coming from untreated mothers but being suckled by ethanol-treated mothers. Alcohol treatment increases the dry weight and lipoprotein lipase activity in the mammary gland, and decreases both absolute and relative mammary gland weight and mammary tissue protein content. The triacylglycerol concentration of milk from treated dams is increased, whereas lactose concentration is decreased in comparison to milk from controls, although the total energy content of milk from alcohol-treated dams is higher than that from controls. Ethanol treatment produces a reduction of daily milk production. Pups nursed by alcoholic mothers show a retarded growth with respect to pups nursed by untreated mothers. Furthermore, they present a reduction in the levels of circulating glucose, insulin, glycerol and free fatty acids, whereas an increase in acetoacetate and in urea levels is observed. Pups from alcoholic mothers show reduced glycogen concentration in the liver while the protein content is increased. Plasma free amino acids in pups nursed by alcoholic mothers are lower than in control pups, the differences in Ala, Glu+Gln, Gly, Pro, 4-OH-Pro, citrulline, Cys, Tyr, Phe and the combined total values being statistically significant. We may therefore draw the conclusion that chronic ethanol treatment impairs lactational performance affecting mammary gland function as shown by the decline in milk production and altered milk composition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of chronic ethanol consumption on lactational performance in rat: mammary gland and milk composition and pups' growth and metabolism. 362 48

Fusarium heterosporum produces a solvent-tolerant lipase. A 1.3-kbp lipase cDNA was isolated from the cDNA library by colony hybridization with an oligonucleotide probe corresponding to the N-terminal amino acid sequence. Nucleotide sequence analysis showed an open reading frame of 999 bp, and the deduced amino acid sequence contained the N-terminal sequence determined by Edman degradation and the consensus pentapeptide (-Gly-X-Ser-X-Gly-), which is conserved in lipase, esterase, and serine protease. The mature lipase consisted of 301 amino acid residues with a molecular mass of 32.7 kDa, preceded by the putative signal peptide or preprosequence. The enzyme was homologous to lipases from Humicola lanuginosa (39% homology), Rhizomucor miehei (32%), Rhizopus delemar (32%), and Rhizopus niveus (32%), and to mono- and diacylglycerol lipase from Penicillium camembertii (38%). Comparison of this lipase with these homologous enzymes suggested that the catalytic triad was composed of Ser144, Asp198, and His256, and that the oxyanion hole was formed with Ser 82.
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PMID:Cloning and nucleotide sequence of cDNA encoding a lipase from Fusarium heterosporum. 785 71

A lipase from the latex of Euphorbia characias was purified using a method involving extraction with apolar solvent and adsorption chromatography on silica gel. The lipase (specific activity, 1500 international units/mg of protein) was eluted from silica gel complexes with a lipid. The main protein fraction, which had a molecular mass of 38 kDa, was inactive when dissociated from the lipid fraction. When the lipid and protein fractions were reassociated, 72% of the lipolytic activity was recovered. This lipolytic activity was inhibited by diethyl p-nitrophenyl phosphate, which was shown to bind the lipase with a molar ratio of 0.75. High specific activities (1000 international units/mg) were measured for the lipase of E. characias on lipid extracts rich in galactosyl diacylglycerols. The apolipase was sequenced up to residue 23. The B chain of ricin has a strong homology (43.5%) with that sequence and cross-reacted with antibodies raised against the purified lipase from E. characias. The activity of the B chain of ricin was comparable (54 international units/mg) to that of the apolipase of E. characias (100 international units/mg) mixed with the same lipid cofactor complex. The primary structure (residues 68-72) of the B chain of ricin contains the lipase consensus sequence Gly-Xaa-Ser-Xaa-Gly. Its reactivity with diethyl p-nitrophenyl phosphate indicates the presence of an activated serine that, in addition to its well-documented lectin activity for galactosides, suggests that the B chain of ricin may be a galactosyl diacylglycerol lipase, closely analogous to the lipase from E. characias.
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PMID:Lipases of the euphorbiaceae family: purification of a lipase from Euphorbia characias latex and structure-function relationships with the B chain of ricin. 797 58

The human hormone-sensitive lipase (HSL) gene encodes a 786-aa polypeptide (85.5 kDa). It is composed of nine exons spanning approximately 11 kb, with exons 2-5 clustered in a 1.1-kb region. The putative catalytic site (Ser423) and a possible lipid-binding region in the C-terminal part are encoded by exons 6 and 9, respectively. Exon 8 encodes the phosphorylation site (Ser551) that controls cAMP-mediated activity and a second site (Ser553) that is phosphorylated by 5'-AMP-activated protein kinase. Human HSL showed 83% identity with the rat enzyme and contained a 12-aa deletion immediately upstream of the phosphorylation sites with an unknown effect on the activity control. Besides the catalytic site motif (Gly-Xaa-Ser-Xaa-Gly) found in most lipases, HSL shows no homology with other known lipases or proteins, except for a recently reported unexpected homology between the region surrounding its catalytic site and that of the lipase 2 of Moraxella TA144, an antarctic psychrotrophic bacterium. The gene of lipase 2, which catalyses lipolysis below 4 degrees C, was absent in the genomic DNA of five other Moraxella strains living at 37 degrees C. The lipase 2-like sequence in HSL may reflect an evolutionarily conserved cold adaptability that might be of critical survival value when low-temperature-mobilized endogenous lipids are the primary energy source (e.g., in poikilotherms or hibernators). The finding that HSL at 10 degrees C retained 3- to 5-fold more of its 37 degrees C catalytic activity than lipoprotein lipase or carboxyl ester lipase is consistent with this hypothesis.
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PMID:Gene organization and primary structure of human hormone-sensitive lipase: possible significance of a sequence homology with a lipase of Moraxella TA144, an antarctic bacterium. 850 34


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