Mechanisms involved in the inhibition of glycolysis by cyanide and antimycin A inCandida albicansand its reversal by hydrogen peroxide. A common feature inCandidaspecies

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.

Murburn precepts for lactic‐acidosis, Cori cycle, and Warburg effect: Interactive dynamics of dehydrogenases, protons, and oxygen

“…With this perspective, researchers could further explore the crucial roles of LDH (isozymes) in various clinical contexts. The analyses conducted in this study suggest that the intriguing tetra‐molecular reaction within glycolysis mediated by glyceraldehydes‐3‐phosphate dehydrogenase could be a murzyme type process. This is corroborated by the finding that the enzyme activity is inhibited by cyanide and reversed by peroxide (DROS) (Peña et al, 2015) and the toxicity of cyanide is explained by murburn mechanism (Manoj et al, 2020; Manoj & Bazhin, 2021). …”

A common mechanism explains the induction of aerobic fermentation and adaptive antioxidant response in Phaffia rhodozyma

“…For example, respiratory deficient strains of S. cerevisiae showed a 4-fold increase of NAD(P)H fluorescence compared to native yeast strains [ 103 ]. Candida albicans and Candida dubliniensis exhibited increased levels of NADH fluorescence whereas ATP decreased under the presence of respiratory inhibitors such as cyanide and antimycin A [ 104 ]. In addition, impairment of the electron transport flow can lead to a more reduced redox state in other cell types as well [ 46 , 47 , 49 , 105 – 108 ].…”

Fungicidal Activity of Recombinant Javanicin against Cryptococcus neoformans Is Associated with Intracellular Target(s) Involved in Carbohydrate and Energy Metabolic Processes

“…The selective cellular compartment labeling is a powerful tool for determining cellular events such as mitochondrial staining. Together with the study on energy-relevant metabolic processes would be allocated for measuring the complexity of carbohydrate metabolism, including glycolysis, TCA cycle, as well as electron transport chain [41]. Ultimately, affinity proteomics based on the use of protein-specific detection has been currently introduced as a promising study of the endogenous complex.…”