RESUMO
Eubacterium lentum and phenotypically similar organisms synthesize a steroid 21-dehydroxylase which converts biliary tetrahydrodeoxycorticosterone to pregnanolone. Tetrahydrodeoxycorticosterone, in contrast to pregnanolone, is carcinogenic for hamster embryonic cells (HECT test). In patients with recently diagnosed, untreated sigmoidal or rectal cancer the fecal concentration of 21-dehydroxylating organisms is reduced by more than 99% as compared with age-matched controls. The lack of fecal 21-dehydroxylating organisms, therefore, is a potential marker for the disorder. The role of steroid 21-dehydroxylase in the pathogenesis of colorectal cancer is unknown.
Assuntos
Neoplasias do Colo/metabolismo , Desoxicorticosterona/análogos & derivados , Fezes/análise , Neoplasias Retais/metabolismo , Esteroide 21-Hidroxilase/análise , Esteroide Hidroxilases/análise , Adulto , Idoso , Animais , Transformação Celular Neoplásica , Pré-Escolar , Neoplasias do Colo/microbiologia , Cricetinae , Desoxicorticosterona/análise , Comportamento Alimentar , Feminino , Humanos , Lactente , Pólipos Intestinais/microbiologia , Masculino , Pessoa de Meia-Idade , Testes de Mutagenicidade , New York , Pregnanolona/análise , Neoplasias Retais/microbiologia , Risco , África do SulAssuntos
Ácidos e Sais Biliares/síntese química , Hidroxiesteroide Desidrogenases , Oxazóis/síntese química , Oxirredutases , Bactérias/enzimologia , Ácidos e Sais Biliares/farmacologia , Colelitíase/tratamento farmacológico , Fezes/microbiologia , Humanos , Oxazóis/farmacologia , Esteroide Hidroxilases/antagonistas & inibidoresRESUMO
16 alpha-Hydroxyprogesterone, precursor of biliary 16 alpha-hydroxypregnanolone, was incubated with mixed fecal flora of humans and rats. The major steroid metabolite formed in both systems was 3 alpha-hydroxy-17 alpha-pregnan-20-one. These results demonstrated that the fecal flora reduced the delta 4-3 keto structure, removed the hydroxy group at C-16 and isomerized the side chain from the beta to the alpha configuration. Ring-A reduction of the substrate resulted in a 5 beta-compound with human flora and a 5 alpha-product with rat bacteria. The prevalence of 16 alpha-dehydroxylating organisms varied considerably in human fecal flora and was approximately 10(5)/g of feces in the three rats tested. Rat fecal flora dehydroxylated 16 alpha-hydroxyprogesterone after 4-5 days incubation at 37 degrees C, at pH 6.5-7.5, and with a substrate concentration of 20-80 microgram/ml (optimal condition). Preliminary evidence suggests that 16 alpha-dehydroxylase is exclusively of bacterial origin and is synthesized by an obligate anaerobe.
Assuntos
Fezes/microbiologia , Hidroxiprogesteronas/metabolismo , Adulto , Animais , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Oxirredutases/análise , RatosRESUMO
The permeability of an N-oleoyldihydrosphingomyelin bilayer against glycerol was similar to that of a bilayer of phosphatidylcholine with identical effective hydrophobic chain length. Cholesterol at 1:1 molar ratio reduced the permeability, and also reduced the energy of activation of glycerol penetration, an effect not found for diesterphosphatidylcholine with cholesterol. The higher level of the ground state of the entropy of activation for permeability can be interpreted in terms of a hydrogen belt model which postulates lipid-lipid hydrogen bonding in membranes and explains the effect found as a disturbance of the hydrogen belt structure. Dihydrosphingomyelin can be considered to function as an "extender" in the hydrogen belt network.
