In
enzymology, a formaldehyde dehydrogenase () is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
that
catalyzes the
chemical reaction
A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...
:formaldehyde + NAD
+ + H
2O
formate + NADH + H
+
The 3
substrates of this enzyme are
formaldehyde
Formaldehyde ( , ) (systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section ...
,
NAD+, and
H2O, whereas its 3
products
Product may refer to:
Business
* Product (business), an item that serves as a solution to a specific consumer problem.
* Product (project management), a deliverable or set of deliverables that contribute to a business solution
Mathematics
* Produ ...
are
formate,
NADH
Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an aden ...
, and
H+.
This enzyme belongs to the family of
oxidoreductase
In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, also called the electron donor, to another, the oxidant, also called the electron acceptor. This group of enzymes usually u ...
s, specifically those acting on the aldehyde or oxo group of donor with NAD+ or NADP+ as acceptor. The
systematic name A systematic name is a name given in a systematic way to one unique group, organism, object or chemical substance, out of a specific population or collection. Systematic names are usually part of a nomenclature.
A semisystematic name or semitrivial ...
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.
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.
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.
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.
Null mice show increased levels of S-nitrosated proteins, increased beta adrenergic receptor numbers in lung and heart,
diminished tachyphylaxis to β2-adrenergic receptor agonists, hyporesponsiveness to
methacholine
Methacholine ( INN, USAN) (trade name Provocholine), also known as Acetyl-β-methylcholine, is a synthetic choline ester that acts as a non-selective muscarinic receptor agonist in the parasympathetic nervous system.
Medical uses
Methacholine ...
and allergen challenge and reduced infarct size after occlusion of the coronary artery.
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.
More related to its alcohol dehydrogenase activity, GSNOR null mice show a 30% reduction in the 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.
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.
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.
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 a ~4-fold increase in gene expression.
Structural studies
As of late 2007, only one
structure has been solved for this class of enzymes, with the
PDB accession code .
References
Further reading
*
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EC 1.2.1
NADH-dependent enzymes
Enzymes of known structure