Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycosides of 3-nitro-1-propanol (nitropropanol) and glucose esters of 3-nitro-1-propanoic acid (nitropropionic acid) occur in many forages distributed throughout the world. Systemically, nitropropionic acid irreversibly inactivates succinate dehydrogenase, thereby blocking ATP formation. Nitropropanol is not toxic per se in mammals but is converted to nitropropionic acid by hepatic alcohol dehydrogenase. Nitrotoxins can be metabolized by rumen microbes, which may provide a mechanism for detoxification. At least 20 different ruminal bacteria are known to metabolize the nitrotoxins, but most appear to play a minor role in detoxification. Evidence suggests that an obligate anaerobic nitro-respiring bacterium, Denitrobacterium detoxificans, may be particularly important in conferring protection to animals consuming the nitrotoxins as this bacterium metabolizes the toxins at rates near those by mixed ruminal populations. Rates of ruminal nitrotoxin metabolism can be enhanced by modifying the rumen environment through dietary manipulations, which suggests in vivo enrichment of competent nitrotoxin-metabolizing bacteria such as D. detoxificans.
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PMID:Toxicity and metabolism of the conjugates of 3-nitropropanol and 3-nitropropionic acid in forages poisonous to livestock. 1576 79

Thermobifida fusca is a moderately thermophilic actinobacterium naturally capable of utilizing lignocellulosic biomass. The B6 strain of T. fusca was previously engineered to produce 1-propanol directly on lignocellulosic biomass by expressing a bifunctional butyraldehyde/alcohol dehydrogenase (adhE2). To characterize the intracellular mechanisms related to the accumulation of 1-propanol, the engineered B6 and wild-type (WT) strains were systematically compared by analysis of the transcriptome and intracellular metabolome during exponential growth on glucose, cellobiose, and Avicel. Of the 18 known cellulases in T. fusca, 10 cellulase genes were transcriptionally expressed on all three substrates along with three hemicellulases. Transcriptomic analysis of cellodextrin and cellulose transport revealed that Tfu_0936 (multiple sugar transport system permease) was the key enzyme regulating the uptake of sugars in T. fusca. For both WT and B6 strains, it was found that growth in oxygen-limited conditions resulted in a blocked tricarboxylic acid (TCA) cycle caused by repressed expression of Tfu_1925 (aconitate hydratase). Further, the transcriptome suggested a pathway for synthesizing succinyl-CoA: oxaloacetate to malate (by malate dehydrogenase), malate to fumarate (by fumarate hydratase), and fumarate to succinate (by succinate dehydrogenase/fumarate reductase) which was ultimately converted to succinyl-CoA by succinyl-CoA synthetase. Both the transcriptome and the intracellular metabolome confirmed that 1-propanol was produced through succinyl-CoA, L-methylmalonyl-CoA, D-methylmalonyl-CoA, and propionyl-CoA in the B6 strain.
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PMID:Systematic analysis of intracellular mechanisms of propanol production in the engineered Thermobifida fusca B6 strain. 2622 14

Nitrate and certain short chain nitrocompounds and nitro-oxy compounds are being investigated as dietary supplements to reduce economic and environmental costs associated with ruminal methane emissions. Thermodynamically, nitrate is a preferred electron acceptor in the rumen that consumes electrons at the expense of methanogenesis during dissimilatory reduction to an intermediate, nitrite, which is primarily reduced to ammonia although small quantities of nitrous oxide may also be produced. Short chain nitrocompounds act as direct inhibitors of methanogenic bacteria although certain of these compounds may also consume electrons at the expense of methanogenesis and are effective inhibitors of important foodborne pathogens. Microbial and nutritional consequences of incorporating nitrate into ruminant diets typically results in increased acetate production. Unlike most other methane-inhibiting supplements, nitrate decreases or has no effect on propionate production. The type of nitrate salt added influences rates of nitrate reduction, rates of nitrite accumulation and efficacy of methane reduction, with sodium and potassium salts being more potent than calcium nitrate salts. Digestive consequences of adding nitrocompounds to ruminant diets are more variable and may in some cases increase propionate production. Concerns about the toxicity of nitrate's intermediate product, nitrite, to ruminants necessitate management, as animal poisoning may occur via methemoglobinemia. Certain of the naturally occurring nitrocompounds, such as 3-nitro-1-propionate or 3-nitro-1-propanol also cause poisoning but via inhibition of succinate dehydrogenase. Typical risk management procedures to avoid nitrite toxicity involve gradually adapting the animals to higher concentrations of nitrate and nitrite, which could possibly be used with the nitrocompounds as well. A number of organisms responsible for nitrate metabolism in the rumen have been characterized. To date a single rumen bacterium is identified as contributing appreciably to nitrocompound metabolism. Appropriate doses of the nitrocompounds and nitrate, singly or in combination with probiotic bacteria selected for nitrite and nitrocompound detoxification activity promise to alleviate risks of toxicity. Further studies are needed to more clearly define benefits and risk of these technologies to make them saleable for livestock producers.
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PMID:Insights on Alterations to the Rumen Ecosystem by Nitrate and Nitrocompounds. 2697 9