fumarates and alpha-glycerophosphoric-acid

A previous report from our laboratory (Collier et al 1993) showed that the elongated tubules of mitochondria in the cytoplasm of cultured chicken embryo fibroblasts collapsed to irregularly shaped structures surrounding the nuclear membrane after a 1 h heat shock treatment. The normal mitochondrial morphology reappeared upon removal of the thermal stress. We have now determined that several changes occurred in mitochondrial-related metabolites under these same heat shock and recovery conditions. Among these were significant decreases in the levels of fumarate and malate and increases in the amounts of aspartate and glutamate. In contrast, other intermediates of the tri-carboxylic acid cycle were unaltered as were levels of ATP and phosphocreatine. The changes observed might result from heat shock-induced changes in enzyme activities of the mitochondria, from alterations in the membrane-embedded specialized carrier proteins that transport metabolites between cytosol and mitochondria or from a disorganization of the electron-transport system normally coupled to oxidative metabolism. The rapid recovery, however, suggested that these changes were transient and readily reversible.

Topics: Adenosine Triphosphate; Animals; Aspartic Acid; Cells, Cultured; Chick Embryo; Citric Acid; Energy Metabolism; Fibroblasts; Fumarates; Glutamic Acid; Glycerophosphates; Glycolysis; Hot Temperature; Ketoglutaric Acids; Malates; Mitochondria; Phosphocreatine; Pyruvates; Stress, Physiological

Setaria digitata, a cattle filarial parasite, is known to have peculiarities such as hydrogen peroxide (H2O2) production, cyanide insensitivity, absence of cytochromes and presence of quinones. Estimation of mitochondrial H2O2 with different substrates and inhibitors showed that salicylhydroxamic acid (SHAM), the alternative oxidase inhibitor, inhibited the H2O2 production maximally. Based on the inhibitory studies with rotenone, antimycin A, o-hydroxydiphenyl, SHAM and 2 thenoyltrifluoroacetone, a mechanism for the electron transport is proposed. Quinone Q8 seems to have a central role, hence inhibitors at the level of quinones might prove to be effective in designing drugs for filariasis.

Topics: Animals; Antimycin A; Biphenyl Compounds; Cyanides; Electron Transport; Filarioidea; Fumarates; Glycerophosphates; Hydrogen Peroxide; Malates; Mitochondria; Quinones; Rotenone; Salicylamides; Succinates; Succinic Acid; Thenoyltrifluoroacetone