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Subsystem: Glutathione-dependent pathway of formaldehyde detoxification

This subsystem's description is:

Formaldehyde is produced at significant levels by abiotic and biological processes (Auerbach et al., 1977; Levy, 1971). For example, formaldehyde is an intermediate formed during the metabolism of methanol or other methylated compounds. Many Gram-negative bacteria generate formaldehyde from methanol via a periplasmic pyrroloquinoline quinone (PQQ)-dependent dehydrogenases (Wilson et al., 2008).

Because this compound can inactivate many cellular components, cells have systems to metabolize formaldehyde (Auerbach et al., 1977; Barber & Donohue, 1998). This Subsystem (SS) encodes a GSH-dependent pathway to metabolize/ detoxify formaldehyde (Barber et al., 1996; Barber & Donohue, 1998), in which:

(i) formaldehyde is added to the thiol of glutathione to form S-hydroxymethylGSH, a reaction which can either occur SPONTANEOUSLY or be facilitated by a glutathione/formaldehyde-activating enzyme (Gfa) (Goenrich et al., 2002)

(ii) S-hydroxymethylGSH is oxidized to S-formyl-GSH by S-(hydroxymethyl)glutathione dehydrogenase (HMG-DH)

(iii) then converted to formate (HCOO2) by S-formyl-GSH hydrolase (FGH)

(iv) Finally, formate is oxidized by formate dehydrogenase to carbon dioxide (not included in this Subsystem, see SS: Formate dehydrogenase)


References

Barber, R. D. and T. J. Donohue (1998). Pathways for transcriptional activation of a glutathione-dependent formaldehyde dehydrogenase gene. J Mol Biol 280(5): 775-84

Cummins I, McAuley K, Fordham-Skelton A, Schwoerer R, Steel PG, Davis BG, Edwards R. 2006. Unique regulation of the active site of the serine esterase S-formylglutathione hydrolase. J Mol Biol, 359(2):422-32

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: 3069-72.

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(20):14514-22

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

Wilson SM, Gleisten MP, Donohue TJ. 2008. Identification of proteins involved in formaldehyde metabolism by Rhodobacter sphaeroides. Microbiology, 154(Pt 1):296-305

Herring CD, Blattner FR. 2004. Global transcriptional effects of a suppressor tRNA and the inactivation of the regulator frmR. J Bacteriol, 186(20):6714-20.

For more information, please check out the description and the additional notes tabs, below

Diagram	Functional Roles	Subsystem Spreadsheet	Description
Group Alias Abbrev. Functional Role Reactions Scenario Reactions GO Literature Subsets Coloring collapsed expanded do not color by cluster by attribute: BS_essential_Kobayashi EC_contribute_to_fitness EC_essential_Blattner EC_essential_Keio EC_essential_Shigen Essential_Gene_Sets_Bacterial HP_candidate_essential_Salama MG_essential_Hutchison_2006 MT_contribute_to_fitness_Rubin PA_candidate_essential_Jacobs PA_essential_PA14_PAO1_Liberati SA_essential_Forsyth SA_essential_Ji SA_essential_merged_Forsyth_and_Ji SP_essential_merged SP_essential_Song SP_essential_Thanassi ST_essential_Knuth CELLO cell_surface established_antibiotic_inhibitor established_antibiotic_target GENE3D iedb_epitopelinearsequence iedb_epitopename in_phage isoelectric_point microarray_sigmaB_regulon molecular_weight mouse_passage_in_THY_18_hours_change PANTHER PDB Phobius PRINTS PROFILE PSORT PSORT_score secreted_protein_signal SignalP similar_to_human SMART SSF structure TIGRFAMs toxin Vibrio_Fe-regulated_Mey2005 Vibrio_Fur-regulated_Mey2005 virulence_associated virulence_associated_by_adhesion_properties_of_mutants virulence_associated_by_evolution_of_epidemic_microarray virulence_associated_by_mutagenesis_and_nematode_killing virulence_associated_by_Rot_expression_analysis virulence_associated_by_screening_mutants_in_murine_model virulence_associated_by_site_specific_mutation virulence_associated_by_vaccination    display  items per page «first  «prev displaying 1 - 1022 of 1022 next»  last» Taxonomy  Pattern  Organism  Domain Variant Variant Codes -1 Subsystem is not present 0 presence unknown * computer assessed variant (not confirmed by annotator) others functional variant [?]  =!= active Gfa HMG-DH FGH FrmR Reg-F S-(hydroxymethyl)glutathione dehydrogenase (EC 1.1.1.284) S-formylglutathione hydrolase (EC 3.1.2.12) Transcriptional regulator, LysR family, in formaldehyde detoxification operon Glutathione-dependent formaldehyde-activating enzyme (EC 4.4.1.22) FrmR: Negative transcriptional regulator of formaldehyde detoxification operon «first  «prev displaying 1 - 1022 of 1022 next»  last» Formaldehyde is produced at significant levels by abiotic and biological processes (Auerbach et al., 1977; Levy, 1971). For example, formaldehyde is an intermediate formed during the metabolism of methanol or other methylated compounds. Many Gram-negative bacteria generate formaldehyde from methanol via a periplasmic pyrroloquinoline quinone (PQQ)-dependent dehydrogenases (Wilson et al., 2008). Because this compound can inactivate many cellular components, cells have systems to metabolize formaldehyde (Auerbach et al., 1977; Barber & Donohue, 1998). This Subsystem (SS) encodes a GSH-dependent pathway to metabolize/ detoxify formaldehyde (Barber et al., 1996; Barber & Donohue, 1998), in which: (i) formaldehyde is added to the thiol of glutathione to form S-hydroxymethylGSH, a reaction which can either occur SPONTANEOUSLY or be facilitated by a glutathione/formaldehyde-activating enzyme (Gfa) (Goenrich et al., 2002) (ii) S-hydroxymethylGSH is oxidized to S-formyl-GSH by S-(hydroxymethyl)glutathione dehydrogenase (HMG-DH) (iii) then converted to formate (HCOO2) by S-formyl-GSH hydrolase (FGH) (iv) Finally, formate is oxidized by formate dehydrogenase to carbon dioxide (not included in this Subsystem, see SS: Formate dehydrogenase) References Barber, R. D. and T. J. Donohue (1998). Pathways for transcriptional activation of a glutathione-dependent formaldehyde dehydrogenase gene. J Mol Biol 280(5): 775-84 Cummins I, McAuley K, Fordham-Skelton A, Schwoerer R, Steel PG, Davis BG, Edwards R. 2006. Unique regulation of the active site of the serine esterase S-formylglutathione hydrolase. J Mol Biol, 359(2):422-32 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: 3069-72. 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(20):14514-22 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 Wilson SM, Gleisten MP, Donohue TJ. 2008. Identification of proteins involved in formaldehyde metabolism by Rhodobacter sphaeroides. Microbiology, 154(Pt 1):296-305 Herring CD, Blattner FR. 2004. Global transcriptional effects of a suppressor tRNA and the inactivation of the regulator frmR. J Bacteriol, 186(20):6714-20.