Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hexose-6-phosphate dehydrogenase (H6PDH-A2; beta-D-glucose:NAD(P)+ oxido-reductase; E.C. 1.1.1.47) of the teleost Fundulus heteroclitus (L.) shows clinal allelic variation along the east coast of North America. Three of the major allelic isozymes have been purified and compared for native molecular weight, subunit molecular weight, isoelectric point, thermal stability, and steady-state kinetic properties (pH 8.0 and 25 degrees C). Significant differences were found among the allelic isozymes for isoelectric point, thermal stability, and some kinetic parameters. The predominant allelic isozyme in northern populations (H6PDH-AcAc) was found to be more sensitive to heat denaturation than were the predominant homozygous allelic isozymes isolated from southern populations (H6PDH-AaAa and H6PDH-AbAb). The H6PDH-AcAc allelic isozyme had both a significantly greater Km for glucose-6-phosphate than did either of the southern phenotypes and a significantly greater Km for NADP+ and Ki of NAD+ than did one of the southern phenotypes (H6PDH-AaAa). While the allelic isozymes are functionally nonequivalent, it is not yet known whether these differences are reflected at higher levels of biological organization.
Mol Biol Evol 1989 Mar
PMID:The allelic isozymes of hexose-6-phosphate dehydrogenase isolated from Fundulus heteroclitus: physical characteristics and kinetic properties. 271 18

17 beta-Hydroxysteroid oxidoreductase, the enzyme that catalyses the interconversion of oestradiol and oestrone, is known to be present in human breast tissue. However, it is not known whether one or more forms of the enzyme is present. Homogenates of breast adipose tissue and breast glandular tissue were fractionated and fractions assayed in the oxidative direction with NAD+ and NADP+ as coenzymes, and in the reductive direction with NADH and NADPH as coenzymes. Ultracentrifugation of homogenates showed that there was membrane-bound activity and soluble activity. The soluble activity was due to a number of forms of the enzyme with different molecular weights, three in breast adipose tissue and two in breast glandular tissue, as shown by fractionation with (NH4)2SO4 followed by chromatography on Sephadex G-200. The forms of the enzyme isolated differed in their affinities for substrates and coenzymes and in the relative rates at which they catalysed the oxidative and reductive reactions. Preliminary experiments with breast tumours showed that they also contained membrane-bound activity and more than one soluble form of the enzyme.
J Mol Endocrinol 1989 Jan
PMID:Multiple forms of 17 beta-hydroxysteroid oxidoreductase in human breast tissue. 276 15

Regulation of beta-oxidation under various metabolic conditions and energy loads was studied by employing a newly developed method for assaying 3-hydroxyacyl-CoA and 2-trans-enoyl-CoA intermediates of fatty acid oxidation. A 66% inhibition of oleate oxidation with a concomitant 68% inhibition of oxygen consumption resulted in a 81% decrease in the carnitine/acyl-carnitine ratio, but the concentrations of 2-trans-enoyl-CoA and 3-hydroxyacyl-CoA esters did not change significantly and the acid-insoluble acyl-CoA content did not change. The acetyl-CoA concentration increased three-fold, however, and there was a simultaneous tendency for the NADH/NAD+ ratio to shift towards oxidation. The results suggest that the main regulatory site of fatty acid oxidation resides at an early step in the pathway. Since the concentrations of the acyl-CoA derivatives identified did not undergo major changes even though the acyl-carnitine concentration changed some rate limitation must already occur at the steps of acyl transport into the mitochondria or the carnitine acyltransferase II.
J Mol Cell Cardiol 1989 Aug
PMID:Energy-linked regulation of mitochondrial fatty acid oxidation in the isolated perfused rat heart. 277 13

The effects of cholera toxin on the coupling of the thyrotropin-releasing hormone (TRH) receptor to a guanine nucleotide-binding (G) protein were examined in a GH3 clonal strain of rat pituitary tumor cells. Incubation of the cells with cholera toxin (50 ng/ml) for 16 hr caused a decrease in [3H]methyl-TRH binding to 59% of the control level and in TRH-stimulated low Km GTPase activity from 143 to 107% of the control level in the membrane-containing fraction. The effects of cholera toxin were time dependent; TRH-stimulated GTPase activity was reduced after a 3-hr incubation, whereas cholera toxin decreased [3H]methyl-TRH binding in the membrane-containing fraction after a 5-hr incubation. These results suggest that the inhibition of TRH-stimulated GTPase activity by cholera toxin treatment is not due to the decrease of receptor binding caused by this toxin. On the other hand, incubation of GH3 cell membranes with preactivated cholera toxin and NAD+ did not substantially alter the binding of [3H]methyl-TRH. In contrast, the cholera toxin-treated membranes demonstrated a partial reduction in the activity of TRH-induced low Km GTPase activity and a 10-fold increase in the concentration of guanine nucleotide required for a half-maximal effect in regulating the TRH receptor affinity for [3H]methyl-TRH. These data suggest that cholera toxin may act directly on a G protein that is associated with TRH-receptors.
Mol Pharmacol 1988 Jun
PMID:Effects of cholera toxin on the coupling of thyrotropin-releasing hormone to a guanine nucleotide-binding protein in cultured GH3 cells. 283 35

The cellular mechanism of action of the cannabimimetic drugs is examined using cultured cells. In membranes from N18TG2 neuroblastoma cells and the neuroblastoma X glioma hybrid cells, NG108-15, the psychoactive cannabinoid drugs and their nantradol analogs could inhibit adenylate cyclase activity. This response was not observed in either the soluble adenylate cyclase from rat sperm or membrane-bound adenylate cyclases from C6 glioma or S49 lymphoma cells. This cellular selectivity provides further evidence for the existence of specific receptors for the cannabimimetic compounds. Receptor-mediated inhibition of adenylate cyclase requires the presence of a guanine nucleotide-binding protein complex, Gi. Gi can be functionally inactivated as a result of an ADP-ribosylation modification catalyzed by pertussis toxin. The present study demonstrates that pertussis toxin treatment of cells abolished the cannabimimetic response in intact cells and in membranes derived therefrom. The action of pertussis toxin required NAD+ as substrate for in vitro modification of neuroblastoma membranes. Furthermore, pertussis toxin was able to catalyze the labeling of a neuroblastoma membrane protein in vitro using [32P] NAD+ under conditions similar to those by which attenuation of the cannabimimetic inhibition of adenylate cyclase could be demonstrated. This evidence demonstrates the requirement for a functional Gi in the action of cannabimimetic drugs.
Mol Pharmacol 1986 Mar
PMID:Involvement of Gi in the inhibition of adenylate cyclase by cannabimimetic drugs. 286 5

The IMP dehydrogenase of Tritrichomonas foetus, a parasitic protozoan incapable of de novo biosynthesis of purine nucleotides, has been purified about 1000-fold to apparent homogeneity. The purified enzyme demonstrated a 20-fold higher substrate turnover rate than the pure IMP dehydrogenase from sarcoma ascites tumor cells. It has a subunit molecular weight of 58,000, aggregates to a size of 380,000 at low ionic strength, and partly dissociates to a molecular weight of 270,000 in high salt concentrations. Unlike the IMP dehydrogenase of bacteria and mammals, the T. foetus enzyme does not require K+ for activity. The analysis of initial velocity and product inhibition data is consistent with a sequential, ordered bi bi kinetic mechanism for the parasite enzyme-catalyzed reaction, in which IMP binds before NAD+ and NADH is released before XMP. This is in contrast to the partially random mechanism of the bacterial enzyme which involves the formation of an enzyme-K+-(IMP) complex. Mycophenolic acid inhibits T. foetus IMP dehydrogenase uncompetitively versus both IMP and NAD+ with an apparent Ki of 9 microM. This value, which is several hundred-fold higher than that for mammalian IMP dehydrogenase, suggests significantly different binding properties of the mycophenolic acid site in T. foetus IMP dehydrogenase, which might be amenable to specific inhibitor design.
Mol Biochem Parasitol 1987 May
PMID:Purification, characterization, and kinetic analysis of inosine 5'-monophosphate dehydrogenase of Tritrichomonas foetus. 288 11

A subcellular fraction enriched 12 times in glycosomes (NAD+-linked alpha-glycerophosphate dehydrogenase) and devoid of detectable contamination from other subcellular components, was prepared from bloodstream Trypanosoma rhodesiense. Using a method employing exposure to toluene as a means of studying normally latent glycosomal enzymes, and phospholipase A2 as a membrane probe, the association of adenylate kinase and alpha-glycerophosphate dehydrogenase with the glycosome was studied. The normally latent glycerophosphate dehydrogenase (NAD+ linked), it is proposed, is an intraglycosomal enzyme having no membrane association, but bound to the core by weak ionic linkages. As such it is possible to release the enzyme from permeable (toluene treated) glycosomes using Cl-, with a resulting 4-fold increase in the Km for dihydroxyacetone phosphate. The presence of Cl- also stimulates an increase in specific activity, but this is observed before any release of enzyme. In contrast adenylate kinase, a non-latent glycosomal enzyme, is clearly membrane associated, the use of phospholipase A2 revealing an absolute dependence on phospholipid for activity. Restoration of activity appears to specifically require phosphatidyl choline and to be co-operative in nature (nH = 1.56). It is proposed that adenylate kinase is an integral glycosomal membrane enzyme, probably affecting the control of intra-glycosomal ADP/ATP levels.
Mol Biochem Parasitol 1985 Feb
PMID:The presence of alpha-glycerophosphate dehydrogenase (NAD+-linked) and adenylate kinase as core and integral membrane enzymes respectively in the glycosomes of Trypanosoma rhodesiense. 298 83

As part of an effort to develop a new means of inducibly inactivating cellular proteins in vivo, three monoclonal antibodies which neutralize yeast alcohol dehydrogenase (ADH) activity were isolated and characterized with respect to criteria important for the inactivation strategy. The significance of these criteria is considered, and a general means of generating appropriate antibodies is suggested. All three antibodies described here were specific for ADH I; they did not recognize the closely related isozyme ADH II in a plate-binding assay and did not immunoprecipitate molecules other than ADH from a Saccharomyces cerevisiae extract. Neutralization occurred in a yeast extract and, for two antibodies, was blocked by high concentrations of the coenzyme NAD+. This finding suggests that the antibodies may block enzyme activity by stabilizing an inactive form of ADH lacking bound NAD+. These results provide a foundation for the use of these antibodies to inactivate ADH in vivo.
Mol Cell Biol 1988 Jun
PMID:Molecular tools for inactivating a yeast enzyme in vivo. 304 87

Hydrogenosomes isolated from Tritrichomonas foetus and Trichomonas vaginalis fermented pyruvate to acetate, malate, H2, and CO2 in an anaerobic process dependent on ADP, Pi, Mg2+, and succinate. The extent to which pyruvate was carboxylated to malate by malate dehydrogenase (decarboxylating) rather than decarboxylated to acetate by pyruvate/ferredoxin oxidoreductase was dependent on pCO2. The processes observed showed carbon and redox balances. The presence of an NADH/ferredoxin oxidoreductase activity was demonstrated. This enzyme is likely to be involved in the transfer of electrons from the ferredoxin reduced in pyruvate oxidation to NAD+ needed for the reductive carboxylation of pyruvate. Disruption of hydrogenosomes with Triton X-100 led to cessation of pyruvate-dependent H2 formation which could be restored by addition of coenzyme A and methyl viologen or ferredoxin. The formation of acetate and H2 by undisrupted hydrogenosomes proceeded at approximately half maximal rates in the presence of 25 microM succinate for T. foetus and 5 microM succinate for T. vaginalis. The apparent Km value of the acetate/succinate CoA transferase from T. foetus for succinate was approximately 45 microM, thus the stimulating effect of succinate might be due to the requirement of this enzyme for succinate. The exact mechanism of this effect remains to be elucidated, however.
Mol Biochem Parasitol 1986 Jul
PMID:Anaerobic pyruvate metabolism of Tritrichomonas foetus and Trichomonas vaginalis hydrogenosomes. 309 Apr 35

The existence of the nuclear enzyme ADP-ribosyl transferase in the filarial worm Onchocerca volvulus was demonstrated. The enzyme activity was observed in the nuclear preparation from the parasitic organism. Poly(ADP-ribose) was identified as the reaction product by the isolation of phosphoribosyl-AMP and 5'AMP as the major products of snake-venom phosphodiesterase digestion. The temperature and pH optima for the enzyme were 25 degrees C and 8.5, respectively. The apparent Km value exhibited by the substrate NAD+, is 750 microM and the activity of the enzyme is inhibited by four chemical classes of inhibitors, nicotinamides, methylxanthines, thymidine and aromatic amides.
Mol Biochem Parasitol 1987 May
PMID:Detection of adenosine diphosphate-ribosyl transferase activity in the filarial worm, Onchocerca volvulus. 311 72


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