Iron deficiency leads to repression of a non‐canonical methionine salvage pathway in Schizosaccharomyces pombe

2020 ◽  
Vol 114 (1) ◽  
pp. 46-65
Author(s):  
Ariane Brault ◽  
Simon Labbé
Keyword(s):  
Iron Deficiency ◽  
Schizosaccharomyces Pombe ◽  
Salvage Pathway ◽  
Methionine Salvage Pathway ◽  
Methionine Salvage

scholarly journals The effect of trichloroethylene metabolites on the hepatic vitamin B12-dependent methionine salvage pathway and its relevance to increased excretion of formic acid in the rat

2020 ◽  
Vol 9 (2) ◽  
pp. 117-126
Author(s):  
Noreen Yaqoob ◽  
Katarzyna M Bloch ◽  
Andrew R Evans ◽  
Edward A Lock
Keyword(s):  
Formic Acid ◽  
Vitamin B12 ◽  
Prior Treatment ◽  
Methionine Synthase ◽  
Acid Excretion ◽  
Salvage Pathway ◽  
Methionine Salvage Pathway ◽  
F344 Rats ◽  
Male F344 Rats ◽  
Methionine Salvage

Abstract The industrial solvent trichloroethylene (TCE) and its two major metabolites trichloroethanol (TCE-OH) and trichloroacetic acid (TCA) cause formic aciduria in male F344 rats. Prior treatment of male F344 rats with 1-aminobenzotriazole a cytochrome P450 inhibitor, followed by TCE (16mk/kg, po), completely prevented formic aciduria, but had no effect on formic acid excretion produced by TCA (8 or 16 mg/kg, po), suggesting TCA may be the proximate metabolite producing this response. Dow and Green reported an increase in the concentration of 5-methyltetrahydrofolate (5-MTHF) in the plasma of rats treated with TCE-OH, suggesting a block in the cycling of 5-MTHF to tetrahydrofolate (THF). This pathway is under the control of the vitamin B12-dependent methionine salvage pathway. We therefore treated rats with three daily doses of methylcobalamin (CH3Cbl) or hydroxocobalamin (OHCbl), a cofactor for methionine synthase, or L-methionine, followed by TCE (16 mg/kg) to determine if they could alleviate the formic aciduria. These pretreatments only partially reduced the excretion of formic acid in the urine. Although prior treatment with S-adenosyl-L-methionine had no effect on formic acid excretion. Consistent with these findings, the activity of methionine synthase in the liver of TCE-treated rats was not inhibited. Transcriptomic analysis of the liver-identified nine differential expressed genes, of note, was downregulation of Lmbrd1 involved in the conversion of vitamin B12 into CH3Cbl, a cofactor for methionine synthase. Our findings indicate that the formic aciduria produced by TCE-OH and TCA may be the result of a block in the recycling of 5-MTHF to THF, the effect on the methionine salvage pathway being a secondary response following acute exposure.

scholarly journals Plausible Novel Ribose Metabolism Catalyzed by Enzymes of the Methionine Salvage Pathway inBacillus subtilis

2013 ◽  
Vol 77 (5) ◽  
pp. 1104-1107 ◽  
Author(s):  
Toshihiro NAKANO ◽  
Yohtaro SAITO ◽  
Akiho YOKOTA ◽  
Hiroki ASHIDA
Keyword(s):  
Salvage Pathway ◽  
Methionine Salvage Pathway ◽  
Methionine Salvage

scholarly journals Metabolic Regulation as a Consequence of Anaerobic 5-Methylthioadenosine Recycling inRhodospirillum rubrum

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Justin A. North ◽  
Jaya Sriram ◽  
Karuna Chourey ◽  
Christopher D. Ecker ◽  
Ritin Sharma ◽  
...  
Keyword(s):  
Rhodospirillum Rubrum ◽  
Anaerobic Growth ◽  
Sulfur Source ◽  
Salvage Pathway ◽  
Anaerobic Conditions ◽  
Protein Levels ◽  
Methionine Salvage Pathway ◽  
Sulfur Containing ◽  
In Cells ◽  
Methionine Salvage

ABSTRACTRhodospirillum rubrum possesses a novel oxygen-independent, aerobic methionine salvage pathway (MSP) for recycling methionine from 5-methylthioadenosine (MTA), the MTA-isoprenoid shunt. This organism can also metabolize MTA as a sulfur source under anaerobic conditions, suggesting that the MTA-isoprenoid shunt may also function anaerobically as well. In this study, deep proteomics profiling, directed metabolite analysis, and reverse transcriptase quantitative PCR (RT-qPCR) revealed metabolic changes in response to anaerobic growth on MTA versus sulfate as sole sulfur source. The abundance of protein levels associated with methionine transport, cell motility, and chemotaxis increased in the presence of MTA over that in the presence of sulfate. Purine salvage from MTA resulted primarily in hypoxanthine accumulation and a decrease in protein levels involved in GMP-to-AMP conversion to balance purine pools. Acyl coenzyme A (acyl-CoA) metabolic protein levels for lipid metabolism were lower in abundance, whereas poly-β-hydroxybutyrate synthesis and storage were increased nearly 10-fold. The knownR. rubrumaerobic MSP was also shown to be upregulated, to function anaerobically, and to recycle MTA. This suggested that other organisms with gene homologues for the MTA-isoprenoid shunt may also possess a functioning anaerobic MSP. In support of our previous findings that ribulose-1,5-carboxylase/oxygenase (RubisCO) is required for an apparently purely anaerobic MSP, RubisCO transcript and protein levels both increased in abundance by over 10-fold in cells grown anaerobically on MTA over those in cells grown on sulfate, resulting in increased intracellular RubisCO activity. These results reveal for the first time global metabolic responses as a consequence of anaerobic MTA metabolism compared to using sulfate as the sulfur source.IMPORTANCEIn nearly all organisms, sulfur-containing byproducts result from many metabolic reactions. Unless these compounds are further metabolized, valuable organic sulfur is lost and can become limiting. To regenerate the sulfur-containing amino acid methionine, organisms typically employ one of several variations of a “universal” methionine salvage pathway (MSP). A common aspect of the universal MSP is a final oxygenation step. This work establishes that the metabolically versatile bacteriumRhodospirillum rubrumemploys a novel MSP that does not require oxygen under either aerobic or anaerobic conditions. There is also a separate, dedicated anaerobic MTA metabolic route inR. rubrum. This work reveals global changes in cellular metabolism in response to anaerobic MTA metabolism compared to using sulfate as a sulfur source. We found that cell mobility and transport were enhanced, along with lipid, nucleotide, and carbohydrate metabolism, when cells were grown in the presence of MTA.

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