Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:026099 (oxidoreductase)
 7,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tyrosine-3-monooxygenase activity [L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] of rat adrenal medulla is induced 20-24 hr after the injection of reserpine (16 mumol/kg intraperitoneally). This and other inducing stimuli increase the 3': 5'-cyclic AMP (cAMP) content in the medulla for longer than 60 min and activate the cAMP-dependent protein kinase (ATP: protein phosphotransferase; EC 2.7.1.37) for several hours. Corticotropin (ACTH), dopamine, and propranolol do not induce the monooxygenase, but elicit an increase in the cAMP content of the medulla which fails to activate protein kinase and lasts less than 1 hr. A high- and low-molecular-weight protein kinase are separated by gel filtration from the 20,000 X g pellet extract of adrenal medulla homogenate. The activity of the low-molecular-weight enzyme is expressed as its ability to phosphorylate histone. The protein kinase activity of the pellet is increased between 3 and 17 hr after reserpine injection. Our evidence indicates that this increase is due to a translocation from cytosol to subcellular structures of a kinase that utilizes lysine-rich histone as phosphate acceptor. The protein kinase activity that is extracted from a purified nuclear fraction prepared from the adrenal medulla of rats injected 7 hr previously with reserpine is greater than that extracted from medulla of saline-treated rats.
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PMID:Activation and nuclear translocation of protein kinase during transsynaptic induction of tyrosine 3-monooxygenase. 0 93

Protein methylase III (S-adenosylmethionine:proteinlysine methyltransferase; ED 2.1.1.25) and protein methylase I (S-adenosylmethionine:protein-arginine methyltransferase; EC 2.1.1.23) activities were examined in isolated nuclei and cytosol fraction, respectively, from various hepatomas with different growth rates. The enzyme activities of both enzymes paralleled the rates of tumor growth in fast- and moderately growing hepatomas. The parallelism was more evident with protein methylase I than with protein methylase III. While protein methylase III activity was elevated in the fast- to moderately growing hepatomas, the enzyme that is responsible for demethylating proteins, epsilon-alkyllysinase (epsilon-slkyl-L-lysine:oxygen oxidoreductase; EC 1.5.3.4), had an inverse relationship to the rate of tumor growth, thus suggesting a possible physiological antagonism. When isolated rat liver nuclei were methylated in vitro with S-adenosyl-L-[methyl-14 C]methionine as methyl donor, H2SO4-insoluble protein and histones had almost equal amounts of methyl-14 C incorporated. However, amino acid analysis revealed that methylated arginines are the predominant form of radioactivity in the H2SO4-insoluble protein (product of protein methylase I), while methylated lysines are the major methylated amino acids in the histones (product of protein methylase III). Furthermore, the hydrolysate of the H2SO4-insoluble protein showed four unknown radioactivity peaks on the amino acid analyzer in addition to the known methylated arginine and lysine derivatives.
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PMID:S-adenosylmethionine:protein methyltransferases in hepatomas. 16 78

The NAD-dependent isocitrate dehydrogenase [threo-D(S)-isocitrate:NAD(+) oxidoreductase (decarboxylating); EC 1.1.1.41] from pig heart is a multisubunit enzyme with a molecular weight of approximately 340,000. Electrophoresis of the enzyme in 10% polyacrylamide gels containing sodium dodecyl sulfate reveals two discrete bands with molecular weights of 41,000 and 39,000. The two bands exhibit approximately equal intensity when stained with Coomassie Blue, Amido Black, and Bromophenol Blue, suggesting that these polypeptide chains are present in equimolar quantities in the native enzyme. The same two-band pattern is observed when the sulfhydryl groups of the enzyme are blocked by alkylation with iodoacetate prior to electrophoresis, indicating that sulfhydryl oxidation is not responsible for the observed heterogeneity. Each of the subunits appears as a single band when eluted from the gel and again subjected to electrophoresis under the same conditions. Isocitrate dehydrogenase contains a total of 41 lysine and arginine residues per average subunit of 40,000 daltons. The observation of approximately 80 peptides upon paper chromatography and high voltage electrophoresis of tryptic digests of the enzyme is consistent with the existence of two distinct polypeptide chains. Dansylation yields two NH(2)-terminal amino acid derivatives: dansyl-phenylalanine and dansyl-alanine. It is concluded that the NAD-specific isocitrate dehydrogenase is composed of equal numbers of two nonidentical subunits.
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PMID:Evidence for the presence of two nonidentical subunits in NAD-dependent isocitrate dehydrogenase of pig heart. 20 34

The stereospecificity of hydrogen transfer in the synthesis of saccharopine from alpha-ketoglutarate and L-lysine catalyzed by saccharopine dehydrogenase (N5-(1,3-dicarboxypropyl)-L-lysine: NAD oxidoreductase (L-lysine-forming), EC 1.5.1.7) was examined by using [4A-3H]- and [4B-3H]NADH. The enzyme showed the A-stereospecificity. The NMR analysis of the saccharopine prepared with [4"A-2H]NADH revealed that the label was incorporated into the C-2 of the glutaryl moiety.
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PMID:Stereospecificity of hydrogen transfer in the saccharopine dehydrogenase reaction. 22 50

Methotrexate and [(3)H]methotrexate were conjugated through a carbodiimide-catalyzed reaction to a 70,000 molecular weight poly(L-lysine) in molar ratios of approximately 13 to 1. The cellular uptake of labeled conjugate was far in excess of the uptake of free drug in cells that were either proficient or deficient in methotrexate transport. The conjugate markedly inhibited the growth of PRO(-)3 Mtx(RII) 5-3 Chinese hamster ovary cells, which are known to be drug resistant by virtue of a deficient methotrexate transport. The cells, however, were not inhibited by the same concentrations of free poly(Lys) and free drug. The 100-fold difference in drug concentration needed to inhibit the mutant cells and their corresponding wild type was totally abolished by exposing the methotrexate-resistant cells to methotrexate-poly(Lys). That the drug is carried into the resistant cells as intact drug-poly(Lys) is evident also from the fact that the conjugate is rendered inactive by brief trypsinization in vitro. Because the conjugate fails to inhibit dihydrofolate reductase (5,6,7,8-tetrahydrofolate: NADP(+) oxidoreductase; EC 1.5.1.3) in vitro, it must be concluded that the strong growth inhibitory effect of the conjugate is due to the intracellular hydrolysis of its polymeric backbone, followed by the release inside the cell of a pharmacologically active form of methotrexate. Our date show that in methotrexate-resistant cells the intracellular release of active drug after uptake of conjugate is of the same order of magnitude as the uptake of free drug by transport-proficient cells and, hence, that the drug resistance due to deficient transport can be totally overcome.
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PMID:Conjugation of methotrexate to poly(L-lysine) increases drug transport and overcomes drug resistance in cultured cells. 27 1

Pyruvate was shown to act as an oxo acid substrate in the reverse direction of saccharopine dehydrogenase [epsilon N-(L-glutaryl-2)-L-lysine: NAD oxidoreductase (L-lysine-forming)] reaction. The enzymic condensation product of lysine and pyruvate was isolated and identified as epsilon-N-(L-propionyl-2)-L-lysine by comparison with the synthetic compound. A method for the chemical preparation of diastereoisomers of epsilon-N-(propionyl-2)-L-lysine is also described.
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PMID:Enzymic and chemical synthesis of epilson-N-(L-propionyl-2)-L-lysine. 36 98

Catechol analogs inhibit the activity of lysyl hydroxylase (peptidyllysine, 2-oxyglutarate: oxygen 5-oxidoreductase, EC 1.14.11.4), a microsomal enzyme which catalyzes the transformation of certain lysyl residues in collagen to hydroxylysine. Chick embryo lysyl hydroxylase activity was measured by specific tritium release as tritiated water from an L-[4,5-3H]lysine-labelled unhydroxylated collagen substrate prepared from chick calvaria. Catechol analogs did not bind irreversibly to either enzyme or substrate, as full activity was restored with dialysis. Addition of excess cofactor, Fe2+, ascorbic acid, or alpha-ketoglutarate, did not affect inhibition. Kinetic analysis revealed that with respect to collagen substrate, catechol demonstrated a noncompetitive type of inhibition with a Ki of 15 muM.
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PMID:Inhibition of lysyl hydroxylase by catechol analogs. 40 45

Saccharopine dehydrogenase (N6-(glutar-2-yl)-L-ly-sine:NAD oxidoreductase (L-lysine-forming)) from baker's yeast was purified to homogenicity. The overall purification was about 1,200-fold over the crude extract with a yield of about 24%. The purified enzyme had a sedimentation coefficient (S20,w) of 3.0 S. The molecular weight determinations by sedimentation equilibrium, Sephadex G-100 gel filtration, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis gave a value of about 39,000 and, therefore, saccharopine dehydrogenase is a single polypeptide chain enzyme. A Stokes radius of 27 A and a diffusion constant of 7.9 X 10(-7) cm2 s-1 were obtained from Sephadex gel filtration chromatography. The enzyme had a high isoelectric pH of 10.1. The NH2-terminal sequence was Ala-Ala----. The enzyme possessed 3 cysteine residues/molecule; no disulfide bond was present. Incubation of saccharopine dehydrogenase with p-chloromercuribenzoate or iodoacetate resulted in complete loss of enzyme activity. Whereas the coenzyme and substrates were ineffective in protecting from inactivation by p-chloromercuribenzoate, iodoacetate inhibition was protected by excess coenzyme.
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PMID:Purification and characterization of saccharopine dehydrogenase from baker's yeast. 41 69

Enzyme assays of skin fibroblasts from five children with familial hyperlysinemia from unrelated families are added to the previous report of three children from two unrelated families. In all instances there was a deficiency in lysine-ketoglutarate reductase, saccharopine dehydrogenase, and saccharopine oxidoreductase activities. To complete the studies on the enzymes associated with familial hyperlysinemia, saccharopine oxidoreductase was partially purified from human liver and characterized. The activity did not separate from that of lysine-ketoglutarate reductase or saccharopine dehydrogenase. A simple screening test for familial hyperlysinemia is described based on the evolution of 14CO2 from lysine-14C by skin fibroblasts. The test differentiated, without overlap, seven patients with familial hyperlysinemia from control subjects. The relation of the two genetic entities involving lysine degradation, familial hyperlysinemia and saccharopinuria, is discussed. It is suggested that familial hyperlysinemia, type I, be applied to patients with major defects in lysine-ketoglutarate reductase and saccharopine dehydrogenase, and that familial hyperlysinemia, type II, to be used to designate patients in whom significant amounts of lysine-ketoglutarate reductase are retained. The nomenclature would be consistent with that of an analogous disease, orotic aciduria.
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PMID:Familial hyperlysinemia: enzyme studies, diagnostic methods, comments on terminology. 46 77

L-Lysine-alpha-ketoglutarate reductase (N5-(1,3-dicarboxypropyl)-L-lysine: NADP+ oxidoreductase (L-lysine-forming, EC 1.5.1.8) was purified from rat liver mitochondria to a homogeneous state judged by SDS polyacrylamide gel electrophoresis, and its molecular weight was estimated as 52000. On Sepharose 4B filtration it has a molecular weight of 230 000 and it is suggested that the active enzyme is a tetramer of subunits of similar size. The purified enzyme was clearly separated from saccharopine dehydrogenase (N5-(1,3-dicarboxypropyl)-L-lysine:NAD+ oxidoreductase (L-glutamate-forming, EC 1.5.1.9). The reactions of purified L-lysine-alpha-ketoglutarate reductase favored the forward reaction (saccharopine formation) and the rate of the reverse reaction (lysine formation) was only 3--5% that of the forward reaction. The forward reaction was specific for L-lysine, alpha-ketoglutarate and NADPH and followed Michaelis-Menten kinetics, whereas the dose vs. response curve of the reverse reaction was sigmoidal with saccharopine. Among the amino acids examined, ornithine, leucine and tryptophan inhibited the forward reaction competitively. These results are different from earlier reports on human and yeast enzymes. The fact that rats fed on lysine-deficient diet do not lose weight much is discussed in relation to the properties of this enzyme.
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PMID:Purification and properties of L-lysine-alpha-ketoglutarate reductase from rat liver mitochondria. 68 35


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