Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The merozoite cap protein-1 (MCP-1) of Plasmodium falciparum follows the distribution of the moving junction during invasion of erythrocytes. We have cloned the gene encoding this protein from a cDNA library using a monoclonal antibody. The protein lacks a signal sequence and has no predicted transmembrane domains; none of the antisera reacts with the surfaces of intact merozoites, indicating that the cap distribution is submembranous. MCP-1 is divided into three domains. The N-terminal domain includes a 52-amino-acid region that is highly conserved in a large family of bacterial and eukaryotic proteins. Based on the known functions of two proteins of this family and the pattern of amino acid conservation, it is predicted that this domain may possess oxido-reductase activity, since the active cysteine residue of this domain is invariant in all proteins of the family. The other two domains of MCP-1 are not found in any other members of this protein family and may reflect the specific function of MCP-1 in invasion. The middle domain is negatively charged and enriched in glutamate; the C-terminal domain is positively charged and enriched in lysine. By virtue of its positive charge, the C-terminal domain resembles domains in some cytoskeleton-associated proteins and may mediate the interaction of MCP-1 with cytoskeleton in Plasmodium.
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PMID:Plasmodium falciparum protein associated with the invasion junction contains a conserved oxidoreductase domain. 778 17

The aim of the present study was to examine the effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on mitochondrial respiration in ischemic rat hearts, and to compare the effects between water-soluble pravastatin and lipid-soluble simvastatin. Either vehicle (0.5% carboxymethyl cellulose), pravastatin (2 or 4 mg/kg per day), or simvastatin (1 or 2 mg/kg per day) was orally administered for 3 weeks. Ischemia was induced by ligating the aorta for 60 min in anesthetized open chest rats under artificial respiration. The hearts were removed, mitochondria were isolated, and the respiration was determined by polarography using glutamate and succinate as substrates. When succinate was used as a substrate, the ADP-stimulated respiration (QO3) and ATP production per unit oxygen (ADP/O ratio) were decreased by ischemia. The decreases in QO3 and ADP/O ratio in the pravastatin- and simvastatin-treated groups appeared to be more prominent than those in the vehicle-treated group. This was especially true in the simvastatin-treated group. The ADP-limited respiration (QO4) with succinate in the vehicle-treated heart was slightly increased by ischemia, while that in the pravastatin- or simvastatin-treated hearts was decreased. In conclusion, HMG-CoA reductase inhibitors may result in worsening of myocardial mitochondrial respiration during ischemia.
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PMID:Effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on mitochondrial respiration in ischemic rat hearts. 779 66

Effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin and simvastatin, on mitochondrial respiration in ischemic rat liver were examined. Either vehicle, pravastatin (2 or 4 mg/kg per day), or simvastatin (1 or 2 mg/kg per day) was orally administered for 3 weeks. Liver ischemia was induced by cessation of the systemic circulation for 60 min. Liver mitochondria were isolated and the respiration was determined by polarography using glutamate and succinate as substrates. In the vehicle-treated group, ischemia drcreased ZO3, respiratory control index (RCI: QO3/QO4), and ADP/O ratio. Pretreatments with pravastatin and simvastatin enhanced the decreases in QO3 measured with either glutamate or succinate, and in ADP/O ratio measured with succinate. Because of decreasing QO4, HMG-CoA reductase inhibitors did not modify the changes in RCI due to ischemia. There were no significant differences in respiratory indices between pravastatin- and simvastatin-treated groups. In conclusion, HMG-CoA reductase inhibitors may enhance respiratory impairment of liver mitochondria under pathophysiological conditions, such as ischemia.
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PMID:Influence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on mitochondrial respiration in rat liver during ischemia. 780 87

Coenzyme F430 is the prosthetic group of methyl-coenzyme-M reductase, which catalyses the final step of methane formation in methanogenic bacteria. The coenzyme is a nickel-containing macrocyclic tetrapyrrole of unique structure. We describe the biosynthesis of this nickel porphinoid from L-glutamate via 5-aminolaevulinic acid, uroporphyrinogen III and dihydrosirohydrochlorin, the binding of the coenzyme to methyl-coenzyme-M reductase and the regulation of coenzyme F430 biosynthesis. We end with some evolutionary considerations on the biosynthesis of macrocyclic tetrapyrroles and remarks on the degradation of these compounds under anaerobic conditions.
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PMID:Biosynthesis of coenzyme F430, a nickel porphinoid involved in methanogenesis. 784 54

Higher plants, algae, cyanobacteria and several other photosynthetic and non-photosynthetic bacteria synthesize 5-aminolaevulinate by a tRNA(Glu)-mediated pathway. Glutamate is activated at the alpha-carboxyl by ligation to tRNA(Glu) with an aminoacyl-tRNA synthetase. An NADPH-dependent reductase converts glutamyl-tRNA(Glu) to glutamate 1-semialdehyde, which is finally converted to 5-aminolaevulinate by an aminotransferase. These components are soluble and in plants and algae are located in the chloroplast stroma. In plants and algae the tRNA(Glu) is encoded in chloroplast DNA whereas the enzymes are encoded in nuclear DNA. The tRNA(Glu) has a hypermodified 5-methylaminomethyl-2-thiouridine-pseudouridine-C anticodon and probably plays a role in the light-dark regulation of 5-aminolaevulinate synthesis. Ligation of glutamate to tRNA(Glu) requires ATP and Mg2+ and proceeds via a ternary intermediate. Glutamyl-tRNA(Glu) reduction appears to involve formation of a complex. Glutamate 1-semialdehyde non-enzymically synthesized by reductive ozonolysis from gamma-vinyl GABA is used as substrate by the last enzyme. Glutamate-1-semialdehyde aminotransferase contains pyridoxal phosphate as a prosthetic group. The enzyme is converted to spectrally different forms by treatment with 4,5-diaminovalerate or 4,5-dioxovalerate. The pyridoxamine 5'-phosphate form of the enzyme converts (S)-glutamate 1-semialdehyde to 5-aminolaevulinate via 4,5-diaminovalerate through a bi-bi ping-pong mechanism.
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PMID:Enzymic and mechanistic studies on the conversion of glutamate to 5-aminolaevulinate. 784 60

5-Aminolevulinic acid (ALA) is the universal precursor of tetrapyrroles, such as chlorophyll and heme. The major control of chlorophyll biosynthesis is at the step of ALA formation. In the chloroplasts of plants, as in Escherichia coli, ALA is derived from the glutamate of Glu-tRNA via the two-step C5 pathway. The first enzyme, Glu-tRNA reductase, catalyzes the reduction of Glu-tRNA to glutamate 1-semialdehyde with the release of intact tRNA. The second enzyme, glutamate 1-semialdehyde 2,1-aminomutase, converts glutamate 1-semialdehyde to ALA. To further examine ALA formation in plants, we isolated Arabidopsis genes that encode the enzymes of the C5 pathway via functional complementation of mutations in the corresponding genes of E. coli. The Glu-tRNA reductase gene was designated HEMA and the glutamate 1-semialdehyde 2,1-aminomutase gene, GSA1. Each gene contains two short introns (149 and 241 nucleotides for HEMA, 153 and 86 nucleotides for GSA1). The deduced amino acid sequence of the HEMA protein predicts a protein of 60 kD with substantial similarity (30 to 47% identity) to sequences derived from the known hemA genes from microorganisms that make ALA by the C5 pathway. Purified Arabidopsis HEMA protein has Glu-tRNA reductase activity. The GSA1 gene encodes a 50-kD protein whose deduced amino acid sequence shows extensive homology (55 to 78% identity) with glutamate 1-semialdehyde 2,1-aminomutase proteins from other species. RNA gel blot analyses indicated that transcripts for both genes are found in root, leaf, stem, and flower tissues and that their levels are dramatically elevated by light. Thus, light may regulate ALA, and hence chlorophyll formation, by exerting coordinated transcriptional control over both enzymes of the C5 pathway.
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PMID:Light regulation of chlorophyll biosynthesis at the level of 5-aminolevulinate formation in Arabidopsis. 790 50

In the biosynthetic conversion of glutamate to the tetrapyrrole precursor, delta-aminolevulinic acid (ALA), glutamate is activated at C-1 by glutamyl-tRNA synthetase-catalyzed ligation to tRNAGlu. Glutamyl-tRNA reductase next catalyzes reduction of the activated glutamate to glutamate-1-semialdehyde (GSA), which is then converted to ALA by GSA aminotransferase. Glutamyl-tRNA synthetase is known to require a divalent metal (usually Mg2+) for activity, but it has not been established whether Mg2+ or another metal ion is also required for glutamyl-tRNA reductase or GSA aminotransferase, because these enzymes have previously been assayed in combined incubations containing all factors required for conversion of glutamate to ALA. We now report the metal requirements individually for each of the three enzyme reactions. Glutamyl-tRNA reductase activity in extracts from both Chlorella vulgaris and Synechocystis sp. PCC 6803 was stimulated by Mg2+ and inhibited by EDTA. EDTA-pretreated Chlorella glutamyl-tRNA reductase-containing fraction had very little activity in the absence of added Mg2+, but recovered full activity in incubations containing added Mg2+. The divalent metal requirement could be met by Mg2+, Mn2+, or Ca2+. Maximum activity was reached at approximately 15 mM concentration of each of these metals, and higher concentrations were inhibitory. Zn2+ was inhibitory at micromolar concentrations. Chlorella glutamyl-tRNA synthetase showed a metal requirement that could be met by Mg2+ or Mn2+, but not Ca2+. Maximum activity was reached at approximately 15 mM Mg2+ or Mn2+. Although the presence of 10 mM Ca2+ did not affect the Mg2+ concentration optimum, Ca2+ increased the effectiveness of low concentrations of Mg2+. In contrast to glutamyl-tRNA synthetase and glutamyl-tRNA reductase, Chlorella GSA aminotransferase did not show a metal requirement or inhibition by EDTA. However, EDTA decreased nonenzymatic transformation of GSA to ALA.
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PMID:Metal requirements of the enzymes catalyzing conversion of glutamate to delta-aminolevulinic acid in extracts of Chlorella vulgaris and Synechocystis sp. PCC 6803. 791 10

5-Aminolevulinic acid for chlorophyll synthesis in greening barley is formed from glutamate. One of the steps involved in the conversion of glutamate to 5-aminolevulinic acid involves a reduction of glutamyl-tRNA(Glu) to glutamate 1-semialdehyde and tRNA(Glu). An enzyme catalysing this reduction was purified from the stroma of greening barley chloroplasts. An approximately 270-kDa protein composed of 54-kDa identical subunits was identified as the barley glutamyl-tRNA(Glu) reductase after purification by Sephacryl S-300, Cibacron Blue-Sepharose, 2'-5'-ADP-Sepharose, Mono S, Mini Q and Superose 12 chromatography. The sequence of 18 amino acids from the N-terminus of the reductase is 50% identical to a cDNA-deduced domain of the Arabidopsis thaliana hemA protein and encoded in a barley hemA cDNA sequence. This is an unequivocal demonstration that the glutamyl-tRNA(Glu) reductase subunit of higher plants is encoded in a hemA gene of the nuclear genome. Heme at 4 microM concentration or glutamate 1-semialdehyde at 200 microM caused a 50% inhibition of the reductase activity. Micromolar concentrations of Zn2+, Cu2+ and Cd2+ also inhibited barley glutamyl-tRNA(Glu) reductase.
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PMID:Purification and partial characterisation of barley glutamyl-tRNA(Glu) reductase, the enzyme that directs glutamate to chlorophyll biosynthesis. 795 67

The sodium-dependent transport of anionic amino acids is suppressed in NIH3T3 cells that constitutively express ras oncogenes. In a model of NIH3T3 cells in which ras expression is triggered in the presence of dexamethasone, aspartate transport decreases gradually upon dexamethasone treatment and is almost completely suppressed after two days of incubation in the presence of the steroid. In the same cell model, lovastatin, an inhibitor of beta hydroxy-beta methyl-glutaryl-CoA-reductase and, hence, of farnesylation of p21ras, partially protects aspartate transport from the inhibition observed upon steroid treatment. Determinations of cell glutamate in ras-expressing and non expressing cells indicate that in both cell models glutamate decreases when extracellular medium is depleted of glutamine. However, this decrease is much faster in cells expressing ras (either constitutively or conditionally). It is proposed i) that cell production of oncogenic p21ras hinders sodium-dependent transport of anionic amino acids and ii) that the transport alteration impairs the maintenance of cell levels of glutamate in ras-expressing cells.
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PMID:Anionic amino acid transport in ras- transformed fibroblasts. 799 52

In Arabidopsis thaliana (L.) Heynh. proline can account for up to 20% of the free amino acid pool after salt stress. Proline accumulation occurs in plants mainly by de novo synthesis from glutamate. The last step of the proline biosynthetic pathway is catalyzed by pyrroline-5-carboxylate (P5C) reductase. A gene (AT-P5C1) encoding this enzyme in A. thaliana has been cloned and sequenced. Expression of AT-P5C1 in Escherichia coli resulted in the complementation of a proC mutant to prototrophy. A comparison of the AT-P5C1 primary and secondary structures with those of six P5C reductase of other organisms is presented. With the exception of several functionally important amino acid residues, little conservation in the primary structure is seen; much greater similarity exists in the putative secondary structure. The AT-P5C1 protein is probably cytosolic. Under normal growth conditions, the P5C reductase mRNA level was significantly higher in roots and ripening seeds than in green tissue. A salt treatment of A. thaliana plants resulted in a 5-fold induction of the AT-P5C1 transcript, suggesting osmoregulation of the AT-P5C1 promoter region. Moreover, a time-course experiment indicated that this induction precedes proline accumulation.
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PMID:Osmoregulation of a pyrroline-5-carboxylate reductase gene in Arabidopsis thaliana. 802 35


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