This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: formaldehyde oxidation II (GSH-dependent)
|Superclasses:||Degradation/Utilization/Assimilation → C1 Compounds Utilization and Assimilation → Formaldehyde Oxidation|
The detoxification of the highly toxic formaldehyde is a major biochemical necessity for most life forms. In the case of methylotrophic bacteria, formaldehyde is not just a toxic compound, but also a central intermediate. It has been suggested that the formaldehyde concentration in the cytoplasm of a methylotroph would rise to 100mM in less than 1 minute if formaldehyde consumption would stop [Vorholt00]. Several different pathways for Formaldehyde Oxidation are known in bacteria, encoded by unrelated or distantly related genes.
About This Pathway
Perhaps the best characterized is the pathway involving NAD- and glutathione-dependent formaldehyde dehydrogenase (GSH-FDH) and S-formylglutathione hydrolase (FGH). GSH-FDH enzymes are a well studied class of the alcohol dehydrogenase protein family (class III ADH ) [Holmquist91] that have been discovered in both prokaryotes and eukaryotes. Unlike many alcohol dehydrogenase enzymes, GSH-FDH do not exhibit appreciable activity with short aliphatic alcohols. Instead, GSH-FDH enzymes catalyze the NAD-dependent oxidation of long-chain alcohols or hydroxylated fatty acids. Specifically, S-hydroxymethylglutathione (HMGSH), an adduct formed spontaneously by glutathione (GSH) and formaldehyde (HCHO) , is both the preferred in vitro and presumed in vivo substrate for GSHFDH enzymes. Even though it is formed spontaneously, in certain bacteria S-hydroxymethylglutathione production is accelerated by a dedicated enzyme, S-(hydroxymethyl)glutathione synthase [Barber96, Harms96, Hoog, Yurimoto03, Ras95, Sanghani02a].
Superpathways: superpathway of C1 compounds oxidation to CO2
Unification Links: EcoCyc:PWY-1801
Gonzalez06: Gonzalez CF, Proudfoot M, Brown G, Korniyenko Y, Mori H, Savchenko AV, Yakunin AF (2006). "Molecular basis of formaldehyde detoxification: Characterization of two s-formylglutathione hydrolases from Escherichia coli, FrmB and YeiG." J Biol Chem 281:14514-14522. PMID: 16567800
Gutheil92: Gutheil WG, Holmquist B, Vallee BL (1992). "Purification, characterization, and partial sequence of the glutathione-dependent formaldehyde dehydrogenase from Escherichia coli: a class III alcohol dehydrogenase." Biochemistry 1992;31(2);475-81. PMID: 1731906
Harms96: Harms N, Ras J, Reijnders WN, van Spanning RJ, Stouthamer AH (1996). "S-formylglutathione hydrolase of Paracoccus denitrificans is homologous to human esterase D: a universal pathway for formaldehyde detoxification?." J Bacteriol 178(21);6296-9. PMID: 8892832
Holmquist91: Holmquist B, Vallee BL (1991). "Human liver class III alcohol and glutathione dependent formaldehyde dehydrogenase are the same enzyme." Biochem Biophys Res Commun 178(3);1371-7. PMID: 1872853
Ras95: Ras J, Van Ophem PW, Reijnders WN, Van Spanning RJ, Duine JA, Stouthamer AH, Harms N (1995). "Isolation, sequencing, and mutagenesis of the gene encoding NAD- and glutathione-dependent formaldehyde dehydrogenase (GD-FALDH) from Paracoccus denitrificans, in which GD-FALDH is essential for methylotrophic growth." J Bacteriol 177(1);247-51. PMID: 7798140
Sanghani02a: Sanghani PC, Robinson H, Bosron WF, Hurley TD (2002). "Human glutathione-dependent formaldehyde dehydrogenase. Structures of apo, binary, and inhibitory ternary complexes." Biochemistry 41(35);10778-86. PMID: 12196016
Vorholt00: Vorholt JA, Marx CJ, Lidstrom ME, Thauer RK (2000). "Novel formaldehyde-activating enzyme in Methylobacterium extorquens AM1 required for growth on methanol." J Bacteriol 182(23);6645-50. PMID: 11073907
Yurimoto03: Yurimoto H, Lee B, Yano T, Sakai Y, Kato N (2003). "Physiological role of S-formylglutathione hydrolase in C(1) metabolism of the methylotrophic yeast Candida boidinii." Microbiology 149(Pt 8);1971-9. PMID: 12904537
DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114
Goenrich02a: Goenrich M, Bartoschek S, Hagemeier CH, Griesinger C, Vorholt JA (2002). "A glutathione-dependent formaldehyde-activating enzyme (Gfa) from Paracoccus denitrificans detected and purified via two-dimensional proton exchange NMR spectroscopy." J Biol Chem 277(5);3069-72. PMID: 11741920
Gutheil97: Gutheil WG, Kasimoglu E, Nicholson PC (1997). "Induction of glutathione-dependent formaldehyde dehydrogenase activity in Escherichia coli and Hemophilus influenza." Biochem Biophys Res Commun 1997;238(3);693-6. PMID: 9333139
Kuznetsova et al., 2005: Kuznetsova E, Proudfoot M, Sanders SA, Reinking J, Savchenko A, Arrowsmith CH, Edwards AM, Yakunin AF (2005). "Enzyme genomics: Application of general enzymatic screens to discover new enzymes." FEMS Microbiol Rev 29(2);263-79. PMID: 15808744
Lasserre06: Lasserre JP, Beyne E, Pyndiah S, Lapaillerie D, Claverol S, Bonneu M (2006). "A complexomic study of Escherichia coli using two-dimensional blue native/SDS polyacrylamide gel electrophoresis." Electrophoresis 27(16);3306-21. PMID: 16858726
Rajagopala14: Rajagopala SV, Sikorski P, Kumar A, Mosca R, Vlasblom J, Arnold R, Franca-Koh J, Pakala SB, Phanse S, Ceol A, Hauser R, Siszler G, Wuchty S, Emili A, Babu M, Aloy P, Pieper R, Uetz P (2014). "The binary protein-protein interaction landscape of Escherichia coli." Nat Biotechnol 32(3);285-90. PMID: 24561554
Wehner93: Wehner EP, Rao E, Brendel M (1993). "Molecular structure and genetic regulation of SFA, a gene responsible for resistance to formaldehyde in Saccharomyces cerevisiae, and characterization of its protein product." Mol Gen Genet 237(3);351-8. PMID: 8483449
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