“Formaldehyde dehydrogenase”的意思、由来-开放百科全书

In enzymology, a formaldehyde dehydrogenase ({{EC number|1.2.1.46}}) is an enzyme that catalyzes the chemical reaction

The 3 substrates of this enzyme are formaldehyde, NAD⁺, and H₂O, whereas its 3 products are formate, NADH, and H⁺.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the aldehyde or oxo group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is formaldehyde:NAD+ oxidoreductase. Other names in common use include NAD+-linked formaldehyde dehydrogenase, s-nitrosoglutathione reductase (GSNO reductase) and NAD+-dependent formaldehyde dehydrogenase. This enzyme participates in methane metabolism.

Ubiquitous function

S-nitrosoglutathione reductase (GSNOR) is a class III alcohol dehydrogenase (ADH) encoded by the ADH5 gene in humans. It is a primordial ADH that is ubiquitously expressed in plant and animals alike. GSNOR reduces S-nitrosoglutathione (GSNO) to the unstable intermediate, S-hydroxylaminoglutathione, which then rearranges to form glutathione sulfinamide, or in the presence of GSH, forms oxidized glutathione (GSSG) and hydroxyl amine.^[1]^[2]^[3] Through this catabolic process, GSNOR regulates the cellular concentrations of GSNO and plays a central role in regulating the levels of endogenous S-nitrosothiols and controlling protein S-nitrosylation-based signaling. As an example of S-nitrosylation-based signaling, Barglow et al. showed that GSNO selectively S-nitrosylates reduced thioredoxin at cysteine 62.^[4] Nitrosylated thioredoxin, via directed protein-protein interaction, trans-nitrosylates the active site cysteine of caspase-3 thus inactivating caspase-3 and preventing induction of apoptosis.^[5]

As might be expected of an enzyme involved in regulating NO levels and signaling, pleiotropic effects are observed in GSNOR knockout models. Deleting the GSNOR gene from both yeast and mice increased the cellular levels of GSNO and nitrosylated proteins, and the yeast cells showed increased susceptibility to nitrosative stress.^[6] Null mice show increased levels of S-nitrosated proteins, increased beta adrenergic receptor numbers in lung and heart,^[7] diminished tachyphylaxis to β2-adrenergic receptor agonists, hyporesponsiveness to methacholine and allergen challenge and reduced infarct size after occlusion of the coronary artery.^[8]^[9] In addition, null mice show increased tissue damage and mortality following challenge with bacteria or endotoxin and are hypotensive under anesthesia yet normotensive in the conscious state.^[10] More related to its alcohol dehydrogenase activity, GSNOR null mice show a 30% reduction in the LD50 for formaldehyde and a decreased capacity to metabolize retinol, although it is clear from these studies that other pathways exist for the metabolism of these compounds.^[11]^[12]

Role in disease

It has been shown that GSNOR may have an important role in respiratory diseases such as asthma. GSNOR expression has been inversely correlated with s-nitrosothiol (SNO) levels in the alveolar lining fluid in the lung and with responsiveness to methacholine challenge in patients with mild asthma compared to normal subjects.^[13] Furthermore, there are lowered SNOs in tracheal irrigations in asthmatic children with respiratory failure in comparison to normal children undergoing elective surgery and NO species are elevated in asthma patients when exposed to antigen.^[14]

Assessing the gene expression of the ADHs in nonalcoholic steatohepatitis (NASH) patients has shown elevated levels of all ADHs, but primarily ADH1 and ADH4 (up to 40-fold increased). ADH5 showed an ~4-fold increase in gene expression.^[15]

Structural studies

As of late 2007, only one structure has been solved for this class of enzymes, with the PDB accession code {{PDB link|1KOL}}.

References

1. ^{{cite journal |vauthors=Jensen DE, Belka GK, Du Bois GC | title = S-Nitrosoglutathione is a substrate for rat alcohol dehydrogenase class III isoenzyme | journal = Biochem. J. | volume = 331 | issue = 2| pages = 659–68 |date=April 1998 | pmid = 9531510 | pmc = 1219401 | doi = }}
2. ^{{cite journal |vauthors=Hedberg JJ, Griffiths WJ, Nilsson SJ, Höög JO | title = Reduction of S-nitrosoglutathione by human alcohol dehydrogenase 3 is an irreversible reaction as analysed by electrospray mass spectrometry | journal = Eur. J. Biochem. | volume = 270 | issue = 6 | pages = 1249–56 |date=March 2003 | pmid = 12631283 | doi = 10.1046/j.1432-1033.2003.03486.x}}
3. ^{{cite journal |vauthors=Staab CA, Alander J, Morgenstern R, Grafström RC, Höög JO | title = The Janus face of alcohol dehydrogenase 3 | journal = Chem. Biol. Interact. | volume = 178 | issue = 1–3 | pages = 29–35 |date=March 2009 | pmid = 19038239 | doi = 10.1016/j.cbi.2008.10.050 }}
4. ^{{cite journal |vauthors=Barglow KT, Knutson CG, Wishnok JS, Tannenbaum SR, Marletta MA | title = Site-specific and redox-controlled S-nitrosation of thioredoxin | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 108 | issue = 35 | pages = E600–6 |date=August 2011 | pmid = 21849622 | doi = 10.1073/pnas.1110736108 | pmc=3167493}}
5. ^{{cite journal |vauthors=Mitchell DA, Marletta MA | title = Thioredoxin catalyzes the S-nitrosation of the caspase-3 active site cysteine | journal = Nat. Chem. Biol. | volume = 1 | issue = 3 | pages = 154–8 |date=August 2005 | pmid = 16408020 | doi = 10.1038/nchembio720 }}
6. ^{{cite journal |vauthors=Liu L, Hausladen A, Zeng M, Que L, Heitman J, Stamler JS | title = A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans | journal = Nature | volume = 410 | issue = 6827 | pages = 490–4 |date=March 2001 | pmid = 11260719 | doi = 10.1038/35068596 }}
7. ^{{cite journal |vauthors=Whalen EJ, Foster MW, Matsumoto A, Ozawa K, Violin JD, Que LG, Nelson CD, Benhar M, Keys JR, Rockman HA, Koch WJ, Daaka Y, Lefkowitz RJ, Stamler JS | title = Regulation of beta-adrenergic receptor signaling by S-nitrosylation of G-protein-coupled receptor kinase 2 | journal = Cell | volume = 129 | issue = 3 | pages = 511–22 |date=May 2007 | pmid = 17482545 | doi = 10.1016/j.cell.2007.02.046 }}
8. ^{{cite journal |vauthors=Que LG, Liu L, Yan Y, Whitehead GS, Gavett SH, Schwartz DA, Stamler JS | title = Protection from experimental asthma by an endogenous bronchodilator | journal = Science | volume = 308 | issue = 5728 | pages = 1618–21 |date=June 2005 | pmid = 15919956 | pmc = 2128762 | doi = 10.1126/science.1108228 }}
9. ^{{cite journal |vauthors=Lima B, Lam GK, Xie L, Diesen DL, Villamizar N, Nienaber J, Messina E, Bowles D, Kontos CD, Hare JM, Stamler JS, Rockman HA | title = Endogenous S-nitrosothiols protect against myocardial injury | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 106 | issue = 15 | pages = 6297–302 |date=April 2009 | pmid = 19325130 | pmc = 2669330 | doi = 10.1073/pnas.0901043106 }}
10. ^{{cite journal |vauthors=Liu L, Yan Y, Zeng M, Zhang J, Hanes MA, Ahearn G, McMahon TJ, Dickfeld T, Marshall HE, Que LG, Stamler JS | title = Essential roles of S-nitrosothiols in vascular homeostasis and endotoxic shock | journal = Cell | volume = 116 | issue = 4 | pages = 617–28 |date=February 2004 | pmid = 14980227 | doi = 10.1016/S0092-8674(04)00131-X}}
11. ^{{cite journal |vauthors=Molotkov A, Fan X, Deltour L, Foglio MH, Martras S, Farrés J, Parés X, Duester G | title = Stimulation of retinoic acid production and growth by ubiquitously expressed alcohol dehydrogenase Adh3 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 99 | issue = 8 | pages = 5337–42 |date=April 2002 | pmid = 11959987 | pmc = 122770 | doi = 10.1073/pnas.082093299 }}
12. ^{{cite journal |vauthors=Deltour L, Foglio MH, Duester G | title = Metabolic deficiencies in alcohol dehydrogenase Adh1, Adh3, and Adh4 null mutant mice. Overlapping roles of Adh1 and Adh4 in ethanol clearance and metabolism of retinol to retinoic acid | journal = J. Biol. Chem. | volume = 274 | issue = 24 | pages = 16796–801 |date=June 1999 | pmid = 10358022 | doi = 10.1074/jbc.274.24.16796| url = }}
13. ^{{cite journal |vauthors=Que LG, Yang Z, Stamler JS, Lugogo NL, Kraft M | title = S-nitrosoglutathione reductase: an important regulator in human asthma | journal = Am. J. Respir. Crit. Care Med. | volume = 180 | issue = 3 | pages = 226–31 |date=August 2009 | pmid = 19395503 | pmc = 2724715 | doi = 10.1164/rccm.200901-0158OC }}
14. ^{{cite journal | author = Dweik RA | title = The promise and reality of nitric oxide in the diagnosis and treatment of lung disease | journal = Cleve Clin J Med | volume = 68 | issue = 6 | pages = 486, 488, 490, 493 |date=June 2001 | pmid = 11405609 | doi = }}
15. ^{{cite journal |vauthors=Baker SS, Baker RD, Liu W, Nowak NJ, Zhu L | title = Role of alcohol metabolism in non-alcoholic steatohepatitis | journal = PLoS ONE | volume = 5 | issue = 3 | pages = e9570 | year = 2010 | pmid = 20221393 | pmc = 2833196 | doi = 10.1371/journal.pone.0009570 }}

Ubiquitous function

Role in disease

Structural studies

References

Further reading