Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arsenic is a well-established human carcinogen that is chronically consumed in drinking water by millions of people worldwide. Recent evidence has suggested that arsenic is a genotoxic carcinogen. Furthermore, we have shown that mitochondria mediate the mutagenic effects of arsenic in mammalian cells, as arsenic did not induce nuclear mutations in mitochondrial DNA (mtDNA)-depleted cells. Using the human-hamster hybrid A(L) cells, we show here that arsenic alters mitochondrial function by decreasing cytochrome c oxidase function and oxygen consumption but increasing citrate synthase function. These alterations correlated with depletion in mtDNA copy number and increase in large heteroplasmic mtDNA deletions. In addition, mtDNA isolated periodically from cultures treated continuously with arsenic did not consistently display the same deletion pattern, indicating that the mitochondrial genome was subjected to repeated and continuous damage. These data support the theory that the mitochondria, and particularly mtDNA, are important targets of the mutagenic effects of arsenic in mammalian cells.
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PMID:Arsenic induced mitochondrial DNA damage and altered mitochondrial oxidative function: implications for genotoxic mechanisms in mammalian cells. 1754 3

The objective of the present investigation was to understand the impact of exogenously applied melatonin on mitochondrial respiration and sugar metabolism in two contrasting rice cultivars, viz., Khitish (arsenic-susceptible) and Muktashri (arsenic-tolerant) under arsenic-stress. Melatonin effectively restored the level of organic acids like pyruvic acid, malic acid and more particularly citric acid by 33 % in Khitish which were lowered during arsenic-stress, whereas their levels were further elevated in Muktashri to provide energy for defence against arsenic-induced injury. Arsenic-exposure led to a significant inhibition in enzyme activities as well as corresponding transcript level of key respiratory enzymes, viz., pyruvate dehydrogenase, citrate synthase, isocitrate dehydrogenase, succinate dehydrogenase and malate dehydrogenase, intriguingly more prominently in case of Khitish. Conversely, melatonin supplementation, irrespective of cultivars, considerably improved the activity of the above enzymes and corresponding gene expressions during stress, indicating acceleration in the rate of Krebs cycle. Melatonin supplementation also stimulated the accumulation of total soluble sugars by 62 % and 25 %, reducing sugars by 50 % and 44 % and non-reducing sugars by 75 % and 14 % in Khitish and Muktashri respectively, concomitant with higher activities of acid invertase, sucrose synthase and sucrose phosphate synthase enzymes, along with the expression of corresponding genes. Enhanced starch accumulation via regulation of alpha amylase and starch phosphorylase activities and gene expression, by melatonin also contributed towards better stress tolerance. Overall, this work illustrated the efficacy of melatonin in the regulation of representative organic acids and enzymes of respiratory cycle along with starch and sugar metabolism in rice cultivars under arsenic toxicity.
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PMID:Exogenous supplementation of melatonin alters representative organic acids and enzymes of respiratory cycle as well as sugar metabolism during arsenic stress in two contrasting indica rice cultivars. 3306 98