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| biopax3:comment |
Aldehyde dehydrogenases catalyze the pyridine nucleotide-dependent oxidation of aldehydes to acids |CITS: [12616643]|. Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme |CITS: [3582651]| that has relatively high affinity for acetaldehyde such that under physiological conditions it mediates essentially all hepatic acetaldehyde oxidation. The active enzyme is a homotetramer |CITS:[12081471]| and exhibits a relatively low Km for acetaldehyde (0.2 +/- 0.02 uM) |CITS: [8155713]|. By comparison, the liver cytosolic aldehyde dehydrogenase isoenzyme (ALDH-1) has a Km for acetaldehyde that is approximately three orders of magnitude greater |CITS: [8155713]|. ALDH2 is one of three distinct aldehyde dehydrogenase isolated from the human liver |CITS: [3610592] [4065146]|. Isoenzymes are differentiated based on electrophoretic mobility, kinetic properties, and subcellular localizations. The broader superfamily of human aldehyde dehydrogenases consists of at least 17 distinct enzymes differentiated on the basis of physical properties, tissue distribution, subcellular location, substrate specificity, and cofactor preference. The chromosomal locations and organization of all genes encoding members of this superfamily have been defined |CITS: [12616643] [1306115]|. A variant of the enzyme that results from a single nucleotide polymorphism (SNP) of the ALDH2 gene is found in approximately 50% of the Asian population |CITS: [4015823]|. The SNP is associated with phenotypic reduction of catalytic activity in both heterozygotes and homozygotes. This reduced activity is caused by a structural point mutation at amino acid position 487 resulting in substitution of Lys for Glu (E487K) |CITS: [11398342]|. Reduced ALDH2 activity results in higher acetaldehyde levels after alcohol intake and this is thought to contribute to the flushing and other vasomotor symptoms observed in some Asians after alcohol consumption |CITS: [8903321]|. The reduced catalytic activity of the variant enzyme results from an increased Km for NAD(+) and a decreased specific activity. Heterotetramers of human liver mitochondrial (class 2) aldehyde dehydrogenase have been expressed in Escherichia coli. Km for NAD of recombinant human enzyme increased more than 150-fold. Furthermore, heterotetrameric enzymes exhibited 16-18% of the activity of "wild type" enzyme whilst E487K homotetramers exhibited 8% of native enzyme activtiy, i.e., in heterotetramers composed of both subunit types, the variant subunit was dominant over the wild type |CITS: [11009616] [8940116]|. The structure of bovine mitochondrial aldehyde dehydrogenase 2 has been solved at 2.65A in its free form. The form complexed with NAD+ has also been solved (to 2.75A). The structure consists of three domains; a small three-stranded beta-sheet domain and two dinucleotide-binding domains. The beta sheet plays a role in subunit interactions |CITS: [9195888] [12081471] [10631996]|
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| biopax3:component | |
| biopax3:componentStoichiome... | |
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| biopax3:displayName |
ALDHI
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| biopax3:name |
ALDH class 2,
ALDH-2,
ALDH-E2,
aldehyde dehydrogenase class 2,
aldehyde dehydrogenase, mitochondrial
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| biopax3:standardName |
mitochondrial aldehyde dehydrogenase
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