Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Automatic Gene Ontology annotation based on Rhea mapping
Combined Automated Annotation using Multiple IEA Methods
Human liver mitochondrial aldehyde dehydrogenase: three-dimensional structure and the restoration of solubility and activity of chimeric forms.
Crystal structure of eta-crystallin: adaptation of a class 1 aldehyde dehydrogenase for a new role in the eye lens.
Mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism contributes to the variation in efficacy of sublingual nitroglycerin.
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The Glu504Lys (ALDH2*2) substitution nearly eliminates ALDH2 activity and lowers the catalytic efficiency of GTN metabolism about tenfold, and carriers lack a clinical response to sublingual nitroglycerin.
"We also show that the catalytic efficiency (Vmax/Km) of GTN metabolism of the Glu504 protein is approximately 10-fold higher than that of the Lys504 enzyme."
Inhibition of the oxidative metabolism of 3,4-dihydroxyphenylacetaldehyde, a reactive intermediate of dopamine metabolism, by 4-hydroxy-2-nonenal.
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ALDH2 oxidises the dopamine-derived aldehyde DOPAL to DOPAC, and 4-HNE inhibits that activity at low micromolar concentrations in recombinant enzyme and in brain mitochondria.
"Incubation of human recombinant ALDH2 with 4HNE (1.5-30 microM) yielded inhibition of activity toward DOPAL."
Large-scale proteomics and phosphoproteomics of urinary exosomes.
Role of the general base Glu-268 in nitroglycerin bioactivation and superoxide formation by aldehyde dehydrogenase-2.
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ALDH2 denitrates nitroglycerin to 1,2-glyceryl dinitrate and nitrite and also reduces it to NO; C302S abolishes all activities while E268Q leaves GTN denitration intact despite crippling dehydrogenase and esterase activity.
"Although the C302S mutation led to >90% loss of all enzyme activities, the E268Q mutant exhibited virtually unaffected rates of GTN denitration despite low dehydrogenase and esterase activities."
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The esterase activity runs through the same catalytic cysteine and general base as aldehyde oxidation, is stimulated but not required by NAD, and was measured on the artificial substrate p-nitrophenyl acetate.
"The esterase activity is stimulated by NAD, but the co-factor is not essential for the reaction, which is initiated by nucleophilic attack of the substrate by Cys-302, resulting in formation of a thioester and release of the corresponding alcohol by hydrolysis of the intermediate through activation of water by Glu-268"
Alda-1 is an agonist and chemical chaperone for the common human aldehyde dehydrogenase 2 variant.
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ALDH2 metabolises toxic biogenic and environmental aldehydes including 4-HNE and acrolein, bioactivates nitroglycerin, and its dehydrogenase activity was assayed on a panel of aldehyde substrates including phenylacetaldehyde.
"we examined the concentration dependence of Alda-1 activation at saturating concentrations of acetaldehyde, propionaldehyde, butyraldehyde, benzaldehyde, phenylacetaldehyde, and 4-trans-(N,N-dimethylamino)-cinnamaldehyde (DACA)."
Differences in susceptibility to inactivation of human aldehyde dehydrogenases by lipid peroxidation byproducts.
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ALDH2 has the highest catalytic efficiency of the three best-studied human ALDH isoforms for acrolein, 4-HNE and malondialdehyde, and is also the isoform most readily inactivated by them.
"among the three most studied human ALDH isoforms, ALDH2 showed the highest catalytic efficiency for oxidation of acrolein, 4-hydroxy-2-nonenal (4-HNE), and malondialdehyde"
Vascular bioactivation of nitroglycerin by aldehyde dehydrogenase-2: reaction intermediates revealed by crystallography and mass spectrometry.
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GTN denitration by ALDH2 proceeds through nucleophilic attack of the catalytic cysteine on a terminal nitrate group, giving a thionitrate adduct on Cys-302 seen both crystallographically and by mass spectrometry.
"The structure of the GTN-soaked wild-type protein revealed a thionitrate adduct to Cys-302 as the first reaction intermediate, which was also found by mass spectrometry (MS) experiments."
Human ALDH1B1 polymorphisms may affect the metabolism of acetaldehyde and all-trans retinaldehyde--in vitro studies and computational modeling.
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ALDH2 was used as the positive control for nitroglycerin, acetaldehyde and 4-HNE metabolism in this ALDH1B1 study, and is an established metabolizer of all three.
"ALDH1A1 and ALDH2 were included in experiments as positive controls since they are established metabolizers of all-trans retinaldehyde (ALDH1A1), acetaldehyde (ALDH2), 4-HNE (ALDH2) and nitroglycerin (ALDH2)."
Alda-1 modulates the kinetic properties of mitochondrial aldehyde dehydrogenase (ALDH2).
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Alda-1 lowers the ALDH2 Km for NAD+ 2.4-fold and raises catalytic efficiency 4.4-fold while raising the aldehyde Km 8.6-fold, so it inhibits at low and activates at high aldehyde concentrations.
"the Km for NAD+ decreased by 2.4-fold, and the catalytic efficiency increased 4.4-fold; however, the Km for the aldehyde increased 8.6-fold, thus, diminishing the catalytic efficiency"
Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and cause a multisystem disorder, AMeD syndrome.
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ALDH2 has weak formaldehyde-catabolising activity, and ectopic wild-type ALDH2 abolishes formaldehyde-induced DNA damage in AMeD syndrome patient cells, so ALDH2 contributes to cellular formaldehyde clearance alongside ADH5.
"Ectopic expression of either of the wild-type ADH5 or ALDH2 complementary DNA (cDNA) in the AMeDS cells completely eliminated the induction of formaldehyde-induced DNA damage"
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
Uncovering newly identified aldehyde dehydrogenase 2 genetic variants that lead to acetaldehyde accumulation after an alcohol challenge.
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Two new loss-of-function ALDH2 variants (R101G, R114W) cause flushing and acetaldehyde accumulation in carriers, and the recombinant enzymes have reduced acetaldehyde turnover through loss of oligomerisation (R101G) and lower Vmax (both).
"In vitro studies with recombinant R101G and R114W ALDH2 enzyme showed a reduced efficiency in acetaldehyde metabolism that is unique when compared to E504K or wild-type ALDH2."
Biochemical genetic analysis of human and rodent aldehyde dehydrogenase (ALDH).
Mitochondrial aldehyde dehydrogenase from human liver. Primary structure, differences in relation to the cytosolic enzyme, and functional correlations.
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The enzyme purified from human liver mitochondria has a 500-residue subunit with N-terminal processing heterogeneity, consistent with cleavage of a mitochondrial targeting peptide.
"Near-total lack of conservation of the N-terminal segments may reflect a role of the N-terminal region in signaling the transport of the mitochondrial protein chains."
5-hydroxyindole acetaldehyde to 5-hydroxyindole acetic acid
acetaldehyde + NAD+ => acetate + NADH + H+ [mitochondrial]
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ALDH2 in the mitochondrial matrix catalyses the oxidation of acetaldehyde to acetate with NAD+, acting as a tetramer.
"ALDH2 (aldehyde dehydrogenase) in the mitochondrial matrix catalyzes the reaction of acetaldehyde and NAD+ to form acetate and NADH + H+"
CLPXP binds mitochondrial matrix proteins
LONP1 degrades mitochondrial matrix proteins
LONP1 binds mitochondrial matrix proteins
CLPXP degrades mitochondrial matrix proteins
UniProtKB entry for human ALDH2 (P05091)