90 research outputs found
Role of neutral metabolites in microbial conversion of 3ß-acetoxy-19-hydroxycholest-5-ene into estrone
Biotransformation of 3ß-acetoxy-19-hydroxycholest-5-ene (19-HCA, 6 g) by Moraxella sp. was studied. Estrone (712 mg) was the major metabolite formed. Minor metabolites identified were 5α-androst-1-en-19-ol-3,17-dione (33 mg), androst-4-en-19-ol-3,17-dione (58 mg), androst-4-en-9α,19-diol-3,17-dione (12 mg), and androstan-19-ol-3,17-dione (1 mg). Acidic metabolites were not formed. Time course experiments on the fermentation of 19-HCA indicated that androst-4-en-19-ol-3,17-dione was the major metabolite formed during the early stages of incubation. However, with continuing fermentation its level dropped, with a concomitant increase in estrone. Fermentation of 19-HCA in the presence of specific inhibitors or performing the fermentation for a shorter period (48 h) did not result in the formation of acidic metabolites. Resting-cell experiments carried out with 19-HCA (200 mg) in the presence of α,α'-bipyridyl led to the isolation of three additional metabolites, viz., cholestan-19-ol-3-one (2 mg), cholest-4-en-19-ol-3-one (10 mg), and cholest-5-en-3ß,19-diol (12 mg). Similar results were also obtained when n-propanol was used instead of α,α'-bipyridyl. Resting cells grown on 19-HCA readily converted both 5α-androst-1-en-19-ol-3,17-dione and androst-4-en-19-ol-3,17-dione into estrone. Partially purified 1,2-dehydrogenase from steroid-induced Moraxella cells transformed androst-4-en-19-ol-3,17-dione into estrone and formaldehyde in the presence of phenazine methosulfate, an artificial electron acceptor. These results suggest that the degradation of the hydrocarbon side chain of 19-HCA does not proceed via C22 phenolic acid intermediates and complete removal of the C17 side chain takes place prior to the aromatization of the A ring in estrone. The mode of degradation of the sterol side chain appears to be through the fission of the C17-C20 bond. On the basis of these observations, a new pathway for the formation of estrone from 19-HCA in Moraxella sp. has been proposed
Structure of pregna-4,16-diene-7α,14α-diol-3,20-dione
7α,14α-Dihydroxypregna-4,16-diene-3,20- dione, C21H28O4, Mr = 344.45, orthorhombic, P212121, a = 7.136 (1), b = 12.342 (1), c = 20.049 (3)Å, V= 1765.7 (3)Å3, Z = 4, Dx = 1.295 g cm-3, λ(Cu Kα) = 1.5418Å, μ = 6.7 cm-1, F(000) = 744, T = 293 K, R = 0.048 for 1345 observations. The A ring may be described as in a l α,2β- half-chair conformation or a l α-sofa conformation. The B and C rings adopt normal chair conformations and the D ring has a 14α-envelope conformation. The molecules are held together by a hydrogen bond [O(3)...O(7)= 2.767 Å]
Structure of a steriod fungal metabolite
3α,7 α, 14 α -Trihydroxypregn-16-en-20-one, C21H3204, Mr = 348.48, orthorhombic, P212121, a = 9.211 (1), b = 13.201 (1), c = 16.031 (1) Å, V = 1949.28 (29) Å3, Z = 4, Dx = 1.187 g cm-3, λ(Cu Kα), = 1.5418 Å, μ = 6.07 cm-1, F(000) = 760, T= 293 K, R = 0.061 for 1337 observations. The A, B and C rings adopt normal chair conformations with the D ring in a 14α-envelope conformation. The molecules are held together by two hydrogen bonds [O(3)…O(20) = 2.879 and O(7)…O(14) = 2.612 Å]
Structure of 9α,19-dihydroxy-4-androstene-3,17-dione
C19H26O4, M1 = 318.41, orthorhombic, P212121, a = 10.591 (1), b = 11.133 (1), c = 13.657 (2) Å, V – 1610.29 Å3, Z = 4, Dm (flotation in KI) = 1.301, Dx = 1.313 g cm-3, Mo Kα, Å = 0.7107 Å, μ = 0.85 cm-1, F(000) = 688, T = 293 K, R – 0.057 for 1253 significant reflections. The Å ring is disordered with atoms C(2) and O(19) occupying two possible sites. The molecules are held together by a hydrogen bond [O(9)…O(17) = 2.89 Å]
Monitoring the effect of pyrene on the germination and radial growth of the wild and mutant strains of Rhizopus arrhizus UCP402
3-Ketosteroid 9α-hydroxylase enzymes: Rieske non-heme monooxygenases essential for bacterial steroid degradation
Metabolism of a monoterpene ketone, R-(+)-pulegone-a hepatotoxin in rat
1. R-(+)-Pulegone was administered orally to rats and the urinary metabolites were investigated. Six metabolites were isolated and purified using column and thin layer chromatographic techniques. Metabolites were identified by i.r., n.m.r. and mass spectral analyses. 2. The neutral metabolites isolated from urine of rats treated with pulegone (I) were: pulegol (II), 2-hydroxy-2(1'-hydroxy-1'-methylethyl)-5-methylcyclohexanone (III), 3,6-dimethyl-7a-hydroxy-5,6,7,7a-tetrahydro-2(4H)-benzofuranone (V) and menthofuran (VII). Metabolites II and III were also excreted in conjugated form. 3. Acidic metabolites isolated from urine of rats treated with pulegone (I) were: 5-methyl-2(1'-methyl-1'-carboxyethylidene)cyclohexanone (IV) and 5-methyl-5-hydroxy-2(1'hydroxy-1'-carboxyethyl)cyclohexanone (VI)
Biocatalyst-mediated expansion of ring D in azadirachtin, a potent insect antifeedant from Azadirachta indica
A microorganism identified as Nocardia Sp.capable of converting azadirachtin 1 into three metabolites, viz. 3-deacetylazadirachtin 2, 1-detigloyl-3-deacetyl-azadirachtin-1-ene-3-one 3 and 1-detigloyl-3-deacetyl-11,19-deoxa-12,19-oxa-11-oxo-azadirachtin-1-ene-3-one 4, has been isolated. This is the first report on the functionalization of azadirachtin using biocatalysts wherein two novel, hitherto unknown metabolites have been isolated and characterized
Pulegone mediated hepatotoxicity: evidence for covalent binding of R(+)-[<SUP>14</SUP>C]pulegone to microsomal proteins in vitro
Incubation of R(+)-[14C]pulegone with rat liver microsomes in the presence of NADPH resulted in covalent binding of radioactive material to macromolecules. Covalent binding was much higher in phenobarbital-treated microsomes as compared to 3-methylcholanthrene treated or control microsomes. The Km and Vmax of covalent binding was 0.4 mM and 1.7 nmol min- mg-, respectively. Covalent binding was drastically inhibited (93%) in the presence of piperonyl butoxide. Antibodies to phenobarbital-induced cytochrome P-450 and NADPH-cytochrome P-450 reductase inhibited covalent binding to an extent of 72% and 47%, respectively. Cysteine and semicarbazide also inhibited NADPH dependent binding of radiolabel from R(+)-[14C]pulegone to microsomal proteins. The results suggest the involvement of liver microsomal cytochrome P-450 in the bioactivation of R(+)-pulegone to reactive metabolite(s) which might be responsible for covalent binding to macromolecules resulting in toxicity
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