title: Mechanisms involved in the inhibition of glycolysis by cyanide and antimycin A in Candida albicans and its reversal by hydrogen peroxide. A common feature in Candida species.
abstract: In Candida albicans, cyanide and antimycin A inhibited K(+) transport, not only with ethanol-O2 as the substrate, but also with glucose. The reason for this was that they inhibited not only respiration, but also fermentation, decreasing ATP production. Measurements of oxygen levels in cell suspensions allowed identification of the electron pathways involved. NADH fluorescence levels increased in the presence of the inhibitors, indirectly indicating lower levels of NAD(+) and so pointing to glyceraldehyde-3-phosphate dehydrogenase as the limiting step responsible for the inhibition of glycolysis, which was confirmed by the levels of glycolytic intermediaries. The cyanide effect could be reversed by hydrogen peroxide, mainly due to an activity by which H2O2 can be reduced by electrons flowing from NADH through a pathway that can be inhibited by antimycin A, and appears to be a cytochrome c peroxidase. Therefore, the inhibition of glycolysis by the respiratory inhibitors seems to be due to the decreased availability of NAD(+), resulting in a decreased activity of glyceraldehyde-3-phosphate dehydrogenase. Compartmentalization of pyridine nucleotides in favor of the mitochondria can contribute to explaining the low fermentation capacity of C. albicans. Similar results were obtained with three C. albicans strains, Candida dubliniensis and, to a lower degree, Candida parapsilosis.
authors.affiliation: Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, DF, 04510, México, DF, México apd@ifc.unam.mx.
authors.forename: Antonio
authors.initials: A
authors.lastname: Peña
authors.affiliation: Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, DF, 04510, México, DF, México.
authors.forename: Norma Silvia
authors.initials: NS
authors.lastname: Sánchez
authors.affiliation: Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, DF, 04510, México, DF, México.
authors.forename: Omar
authors.initials: O
authors.lastname: González-López
authors.affiliation: Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, DF, 04510, México, DF, México.
authors.forename: Martha
authors.initials: M
authors.lastname: Calahorra
mesh_terms: D000968:Antimycin A / Q000633:toxicity*; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism*; D003486:Cyanides / Q000633:toxicity*; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D009243:NAD / Q000378:metabolism
chemical_list: D003486:Cyanides; D009243:NAD; D000968:Antimycin A; D006861:Hydrogen Peroxide; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)
keywords: Candida metabolism; cyanide; electron pathways; glycolysis; hydrogen peroxide