Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

beta-Hydroxybutyrate dehydrogenase (EC 1.1.1.30) was purified 145-fold from Mycobacterium phlei ATCC354 by ammonium sulphate fractionation and DEAE-cellulose chromatography. The pH optima for oxidation and reduction reactions were 8.4 and 6.8 respectively. The purified enzyme was specific for NAD, NADH, acetoacetate and D(-)-beta-hydroxybutyrate. Km values for DL-beta-hydroxybutyrate and NAD were 7.4 mM and 0.66 mM respectively. The enzyme was inactivated by mercurial thiol inhibitors and by heat, but could be protected by NADH, Ca2+ and partially by Mn2+. The enzyme did not require metal ions and was insensitive to EDTA, glutathione, dithiothreitol, beta-mercaptoethanol and cysteine.
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PMID:Purification and properties of beta-hydroxybutyrate dehydrogenase from Mycobacterium phlei ATCC354. 2 83

The mechanism of action of isoniazid (INH) on saprophytic and atypical mycobacteria is thought to be different from that on Mycobacterium tuberculosis because higher concentrations are required to be effective in these species. In this investigation, M. phlei was inhibited by INH at a concentration of 25 mug/ml. Benzoic acid hydrazide (BZH) and nicotinic acid hydrazide (NAH) were inhibitory at levels of 300 and 500 mug/ml, respectively. Inhibition by these compounds was not inoculum dependent. An isolated M. phlei mutant resistant to 100 mug of INH per ml (Inh(r)) was inhibited by INH only at concentrations about equal to those inhibitory for BZH and NAH. When NAH and BZH were below their minimal inhibitory concentrations, INH inhibition was antagonized. Hence, there appears to be a single target site for INH in mycobacteria with different affinities for various hydrazide analogs of INH. The increased inhibitory levels required for the atypical and saprophytic species are due to a decreased affinity of the target site for INH in these species. INH also inhibited both the oxidized nicotinamide adenine dinucleotide (NAD(+)) and adenosine 5'-monophosphate stimulation of reduced NAD (NADH) oxidase activity associated with the M. phlei and M. tuberculosis H(37)R(a) electron transport particles. INH did not reverse the NAD(+) stimulation of oxidase activity in the Inh(r) strain of M. phlei. No direct inhibitory effect of INH on NADH oxidase activity was observed. Incubation of M. phlei electron transport particles at 0 degrees C with INH resulted in a dramatic loss of oxidase activity which could have been prevented if NAD(+) were present. However, INH had no effect upon the NADH oxidase when stored with electron transport particles isolated from the Inh(r) strain. Therefore, INH inhibition of regulation and/or stabilization of the electron transport pathway by NAD(+) or adenosine 5'-monophosphate may account, in part, for the lethal action of the drug on mycobacteria.
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PMID:Specificity of isoniazid on growth inhibition and competition for an oxidized nicotinamide adenine dinucleotide regulatory site on the electron transport pathway in Mycobacterium phlei. 19 85

Peroxidase from Mycobacterium tuberculosis H37Rv was purified to homogeneity. The homogeneous protein exhibits catalase and Y (Youatt's)-enzyme activities in addition to peroxidase activity. Further confirmation that the three activities are due to a single enzyme was accomplished by other criteria, such as differential thermal inactivation, sensitivity to different inhibitors, and co-purification. The Y enzyme (peroxidase) was separated from NADase (NAD+ glycohydrolase) inhibitor by gel filtration on Sephadex G-200. The molecular weights of peroxidase and NADase inhibitor, as determined by gel filtration, are 240000 and 98000 respectively. The Y enzyme shows two Km values for both isoniazid (isonicotinic acid hydrazide) and NAD at low and high concentrations. Analysis of the data by Hill plots revealed that the enzyme has one binding site at lower substrate concentrations and more than one at higher substrate concentration. The enzyme contains 6g-atoms of iron/mol. Highly purified preparations of peroxidases from different sources catalyse the Y-enzyme reaction, suggesting that the nature of the reaction may be a peroxidatic oxidation of isoniazid. Moreover, the Y-enzyme reaction is enhanced by O2. Isoniazid-resistant mutants do not exhibit Y-enzyme, peroxidase or catalase activities, and do not take up isoniazid. The Y-enzyme reaction is therefore implicated in the uptake of the drug.
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PMID:The purification and properties of peroxidase in Mycobacterium tuberculosis H37Rv and its possible role in the mechanism of action of isonicotinic acid hydrazide. 24 21

Contrary to the tubercle Bacilli (H37Ra, BCG), Mycobacterium phlei has a ribitol-NAD dehydrogenase (that also oxidizes, although to a lesser extent, erythritol and glycerol). This difference is observed with the Bacteria grown on Sauton's medium, as well as after their adaptation to ribitol. The extracts of all these Mycobacteria reduce, NADP in the presence of glycerol, ribitol or erythritol, though very slowly.
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PMID:[Enzymatic differences in mycobacteria. Ribitol dehydrogenase]. 40 36

3-Hydroxyacyl-CoA dehydrogenase [EC 1.1.1.35] was purified 100-fold to homogeneity from crude extracts of Mycobacterium smegmatis, using ammonium sulfate fractionation, gel filtration, and chromatography on DEAE-cellulose, hydroxyapatite, and NAD-Sepharose 4B columns. Its molecular weight was estimated to be 50,300 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. NADH acted twelve times more efficiently than NADPH as an electron donor for the reduction of 3-ketoacyl-CoA, and there was strict substrate stereospecificity (L form) in the oxidation of 3-hydroxyacyl-CoA. The pH optimum depended upon the direction of reaction, i.e., 6.0 for the oxidation of NADH and 9--10 for the reduction of NAD. The Km values for different thioesters of acetoacetate, i.e., esters of CoA, pantetheine, and acetyl-cysteamine were determined to be 0.036, 1.19, and 44.4 mM, respectively. Antibodies raised against the dehydrogenase of M. smegmatis strongly inhibited the enzyme activity, but did not affect the corresponding dehydrogenase of pig heart. The antibodies were found to inhibit the acetyl-CoA dependent elongation of fatty acids by the crude extract of M. smegmatis. These findings, together with those on the reconstitution of the elongation activity reported previously (Shimakata, T., Fujita, Y., & Kusaka, T. (1977) J. Biochem. 82, 725-732) indicate that 3-hydroxyacyl-CoA dehydrogenase is involved in the acetyl-CoA dependent elongation of fatty acids in M. smegmatis.
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PMID:Purification and characterization of 3-hydroxyacyl-CoA dehydrogenase of Mycobacterium smegmatis. 52 33

Quantitative structure-activity studies have been performed for a series of 2-substituted isonicotinic acid hydrazides by correlating electronic, steric, and lipophilic properties of the substituents with the biological activity date (MIC) from serial dilution tests with Mycobacterium tuberculosis (strain H 37 Rv). The reaction rates for the quaternization of 2-substituted pyridines with methyl iodide were also determined. The rate constants show a similar dependence on the steric and electronic effects of the substituents as the antibacterial activities of the corresponding pyridine-4-carboxylic acid hydrazides. The obtained correlations give evidence that the reactivity of the pyridine nitrogen atom is essential for the biological activity of 2-substituted isonicotinic acid hydrazides and seem to support the hypothesis that isonicotinic acid derivatives are incorporated into an NAD analogue.
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PMID:Mode of action and quantitative structure-activity correlations of tuberculostatic drugs of the isonicotinic acid hydrazide type. 81 22

Reichstein's compound S was successfully converted to prednisolone in a single-step fermentation using a mixed culture of Curvularia lunata and Mycobacterium smegmatis. Introducing additional medium at the time of bacterial inoculation and increasing the M. smegmatis inoculum to 8% were necessary for maximal dehydrogenation of cortisol to prednisolone (86%). However, beef extract, corn-steep solids, and malt extract were inhibitory to the dehydrogenase activity and stimulatory to hydroxylase. Of the vitamins tested, nicotinic acid and riboflavin at 0.2 and 1.13 mg/L, respectively, resulted in maximum transformation of Reichstein's compound S (100%) and optimized prednisolone yields (92%) in the mixed culture. The trace elements present in the medium were sufficient for maximal transformation, and there was no need for an exogenous supply. Addition of ATP, sodium acetate, and NAD inhibited the dehydrogenation reaction.
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PMID:Some nutritional requirements of a mixed culture transforming Reichstein's compound S into prednisolone. 145 67

Isonicotinic acid hydrazide (isoniazid; INH) inhibition of mycolic acid synthesis was studied by using cell extracts from both INH-sensitive and -resistant strains of Mycobacterium aurum. The cell extract of the INH-sensitive strain was inhibited by INH, while the preparation from the INH-resistant strain was not. This showed that the INH resistance of mycolic acid synthesis was not due to a difference in drug uptake or the level of peroxidase activity (similar in both extracts). As INH did not induce accumulation of any labeled intermediates, it is postulated that the drug acts either on production of labeled chain elongation precursors of mycolic acids or an early step of this elongation. The level of inhibition was not changed by addition of NAD or nicotinamide; thus, INH does not act on mycolic acid synthesis as an NAD antimetabolite. Benzoic or acetic acid hydrazides and known or postulated metabolites of INH (i.e., the corresponding acid, aldehyde, or alcohol) were not inhibitors of cell-free mycolic acid synthesis; the complete structure of INH was required, as already known for inhibition of mycobacterial culture growth. Extracts prepared from INH-treated cells showed reduced mycolic acid synthesis, and the inhibition level was not modified by either extensive dialysis or pyridoxal phosphate. This latter molecule efficiently antagonized INH action by reacting rapidly with INH, as shown by differential spectroscopy. Moreover, pyridoxal phosphate did not release inhibition of INH-treated extracts. It is proposed that INH may covalently react with an essential component of the mycolic acid synthesis system.
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PMID:Isoniazid inhibition of mycolic acid synthesis by cell extracts of sensitive and resistant strains of Mycobacterium aurum. 165 50

Mycobacterium vaccae 10 growing in methanol medium synthesizes two inducible alternative NAD(+)-dependent formate dehydrogenases (FDH). In the presence of molybdenum, the dominating form of the enzyme is FDHI with Mr 440 kDa and Km 0.32 mM for sodium formate. FDHI reduced ferricyanide as well as NAD+, and it was reversibly inactivated by formate. NAD+ stabilized FDHI against this inactivation. Under conditions of artificial molybdenum deficiency (tungsten in the medium), the second enzyme (FDHII) appeared with Mr about 93 kDa and Km 8.3 mM for sodium formate, and no FDHI activity was detected. FDHII did not reduce ferricyanide and was not inactivated by formate. The activity of FDHI was restored in tungsten-grown cells by pulse addition of molybdenum under conditions of blocked protein synthesis, suggesting the pre-existence of inactive apo-FDHI.
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PMID:Alternative NAD(+)-dependent formate dehydrogenases in the facultative methylotroph Mycobacterium vaccae 10. 187 9

Fairly pure leprosy bacilli were easily collected from nude mouse foot pad lepromas by the Ficoll density gradient centrifugation and alkali treatment methods. The yield of bacilli available for biochemical study was 42.6%. The density of Mycobacterium leprae was very heterogeneous. The percent of solid bacilli in the light bacilli fraction was 23%; that in the heavy bacilli fraction was 40%. The endogenous respiration activity in the heavy bacilli was greater than that in light bacilli. The average coefficient of respiration in M. leprae was 1 microliter O2/mg X hr. In the whole cells of M. leprae, a cytochrome b1 absorption peak and its Soret peak were detected at wavelengths of 560 nm and 426 nm, respectively. However, a cytochrome a2-like peak (which was observed in M. lepraemurium), and a cyt c and cyt a were not detected. Catalase activity was not found in whole cells, the cell-free extract, or particle fractions of M. leprae. Any catalase activity associated with M. leprae suspensions is a tissue contaminant. NAD-peroxidase activity was also not detected in the cell-free extract of the leprosy bacillus. These results would indicate that leprosy bacilli cannot degrade hydrogen peroxide.
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PMID:Respiration in Mycobacterium leprae. 300 14


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