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

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

Literature ReferencesMolecular basis of formaldehyde detoxification. Characterization of two S-formylglutathione hydrolases from Escherichia coli, FrmB and YeiG. Gonzalez CF The Journal of biological chemistry 2006 May 1916567800
S-formylglutathione hydrolase of Paracoccus denitrificans is homologous to human esterase D: a universal pathway for formaldehyde detoxification? Harms N Journal of bacteriology 1996 Nov8892832
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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