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Biochem Biophys Res Commun ; 40(6): 1507-13, Sept. 30, 1970.
Artigo em Inglês | MedCarib | ID: med-9248


Previous findings in the literature that rhein inhibits DPNH-linked mitochondrial oxidations by acting in the DPNH dehydrogenase region of the respiratory chain have been confirmed and extended. In the micromolar range rhein inhibits DPNH oxidase and DPNH-ferricyanide activities and the energy-linked reduction of DPNH by succinate in membrane preparations from heart, as wellas the DPNH dehydrogenase and transhydrogenase activities of the soluble, purified enzyme. The inhibition of the activities of the soluble enzyme are purely competitive with respect to substrate. These facts localize the primary inhibition site of rhein between substrate and FMN. In heart ETP a second noncompetitive inhibition is also present but is detectable only at very low (<10æM) rhein concentrations. Rhein also inhibits DPNH dehydrogenase in Candida utilis mitochondria and the purified enzyme from liver. On conversion of the heart enzyme to the low molecule weight DPNH-cytochrome reductase the typical effect of rhein disappears and is replaced by a slight stimulation or inhibition, depending on the electron acceptor used, showing that the substrate binding site is modified in this form of the enzyme. In beef liver mitochondria DPNH oxidation may appear insensitive to rhein, probably because of the strong binding of rhein to other proteins. To a lesser extent unspecific binding of rhein and resultant interference with the inhibition of DPNH dehydrogenase is also shown by BSA and by proteins in heart ETP. Rhein also inhibits transhydrogenations in mitochondria and at higher concentrations lactate and malate dehydrogenases but has no effect on sccinate, alcohol (liver nad yeast), and glucose-6-p dehydrogenases or on Neuospora DPN-ase, glucose-6-phosphatase, and amine oxidase. (SUMMARY)

Humanos , Recém-Nascido , Lactente , Adulto , Antraquinonas/farmacologia , Mitocôndrias Musculares/metabolismo , Oxirredutases/antagonistas & inibidores , Candida/enzimologia , Citocromos , Depressão Química , Transporte de Elétrons , Fibroblastos/citologia , Glucose-6-Fosfatase/antagonistas & inibidores , Glucosefosfato Desidrogenase/antagonistas & inibidores , Cinética , Membranas/enzimologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/enzimologia , Mitocôndrias Hepáticas , Mitocôndrias Musculares/efeitos dos fármacos , Peso Molecular , Miocárdio/citologia , Neurospora/enzimologia , N-Glicosil Hidrolases/antagonistas & inibidores , NAD/metabolismo , Oxirredução , Oxirredutases/isolamento & purificação , Oxirredutases/metabolismo , Polivinil/farmacologia , Ligação Proteica , Saccharomyces/efeitos dos fármacos , Saccharomyces/enzimologia , Soroalbumina Bovina/farmacologia , Solubilidade , Ácidos Sulfúricos/farmacologia