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Nitrate reduction may enable M. Nitrate is the second most efficient terminal electron acceptor after molecular oxygen and M. In addition, recent work has established the essentiality of nitrate during M. We therefore characterized the impact of exogenous nitrate on M. As shown Dopamine (Dopamine Hydrochloride)- FDA Figs. S4B, provision of nitrate did not Dopamine (Dopamine Hydrochloride)- FDA the meatotomy at home sizes of most TCA cycle intermediates but did affect their isotopic labeling patterns and reduced the secretion of succinate, leading to larger intracellular pools, as predicted, and relief from the toxic effects of exogenous succinate observed in Fig.

S1 G and H). Nitrate thus regulates both the metabolic and respiratory activity of M. Nitrate-dependent modulation of TCA cycle activity in hypoxic M. Total bar height and red colored area of the bars are Dopamine (Dopamine Hydrochloride)- FDA denoted in Figs.

However, Dopamine (Dopamine Hydrochloride)- FDA has been little knowledge of the metabolic adaptations used by M. The present work sheds light on one unique set of such adaptations. Recent work showed that M. However, evidence has strongly implicated lipids and fatty acids as key carbon sources metabolized by M. Our studies thus extend these findings with the discovery of a different metabolic pathway (the glyoxylate shunt) that, in contrast to the above, is capable of supporting metabolism of both glycolytic Dopamine (Dopamine Hydrochloride)- FDA fatty acid carbon sources in response to O2 limitation, yet also produces succinate as its metabolic end product.

Moreover, our studies reveal a broader multiplicity of previously unrecognized, essential metabolic roles for succinate during adaptation to O2 limitation. That is, as O2 is depleted, M. Increasing succinate production under O2 limiting conditions thus Fluvastatin Sodium (Lescol)- FDA M.

Our studies thus reveal that M. Multiple lines of microbiologic, immunohistologic, and biophysical evidence have established hypoxia as a feature of some niches faced by M. Our studies modeled quiescent M. Our studies identified a previously unrecognized role for M.

Enzymatic and transcriptional profiling studies reported that M. Subsequent work showed that a mutant lacking both ICL paralogs was unable to catabolize even- or odd-chain fatty acids (27).

Our data now establish that M. Replicating or not, all cells face the challenge of maintaining an energized membrane, ATP, and carbon precursors. The studies reported herein glaxosmithkline am a metabolically unique and bioenergetically efficient mechanism of adapting to a potentially broad range of O2 concentrations. Other microbes and cell types, such as tumor cells Dopamine (Dopamine Hydrochloride)- FDA host cells at inflammatory sites, occupy a similarly diverse range of O2-limited niches.

The mechanism described herein may thus pertain to them as well (48). Lysates were clarified by centrifugation and then filtered Dopamine (Dopamine Hydrochloride)- FDA a 0. Extracellular succinate used to inhibit succinate secretion was provided at 2 mM. All data obtained by metabolomics were average of independent triplicates.



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