ALDH2

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Aldehyde dehydrogenase 2 family (mitochondrial)
Protein ALDH2 PDB 1a4z.png
PDB rendering based on 1a4z.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols ALDH2 ; ALDH-E2; ALDHI; ALDM
External IDs OMIM100650 MGI99600 HomoloGene55480 ChEMBL: 1935 GeneCards: ALDH2 Gene
EC number 1.2.1.3
RNA expression pattern
PBB GE ALDH2 201425 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 217 11669
Ensembl ENSG00000111275 ENSMUSG00000029455
UniProt P05091 P47738
RefSeq (mRNA) NM_000690 NM_009656
RefSeq (protein) NP_000681 NP_033786
Location (UCSC) Chr 12:
112.2 – 112.25 Mb
Chr 5:
121.57 – 121.59 Mb
PubMed search [1] [2]

Aldehyde dehydrogenase 2 family (mitochondrial), also known as ALDH2, is a human gene found on chromosome 12.[1][2]

Function[edit]

The enzyme encoded by this gene belongs to the aldehyde dehydrogenase family of enzymes that catalyze the chemical transformation from acetaldehyde to acetic acid. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism.

\begin{smallmatrix}
             &\text{H}&     &\text{H}&                          &                    &             &\text{H}&     &\text{H}&                      &             &\text{H}&     &        &                          \\
             &      | &     &      | &                          &\mathsf{ADH}        &             &      | &     &      | &\mathsf{ALDH}         &             &      | &     &        &                          \\
\text{H}\,-\!&\text{C}&\!-\!&\text{C}&\!-\,\text{O}\,-\,\text{H}&\xrightarrow{\qquad}&\text{H}\,-\!&\text{C}&\!-\!&\text{C}&\xrightarrow{\qquad\ }&\text{H}\,-\!&\text{C}&\!-\!&\text{C}&\!-\,\text{O}\,-\,\text{H}\\ 
             &      | &     &      | &                          &                    &             &      | &     &     \| &                      &             &      | &     &     \| &                          \\
             &\text{H}&     &\text{H}&                          &                    &             &\text{H}&     &\text{O}&                      &             &\text{H}&     &\text{O}&                          \\
\end{smallmatrix}
Metabolism of alcohol (ethanol) to acetaldehyde (ethanal) and then acetic acid (ethanoic acid)

Isoforms[edit]

Two major liver isoforms of this enzyme, cytosolic and mitochondrial, can be distinguished by their electrophoretic mobilities, kinetic properties, and subcellular localizations. The ALDH2 gene encodes a mitochondrial isoform, which has a low Km for acetaldehydes, and is localized in mitochondrial matrix; in contrast the ALDH1 gene codes for the cytosolic isoform.[3]

Clinical significance[edit]

Most Europeans have two major isozymes, while approximately 50% of Northeast Asians have one normal copy of the ALDH2 gene and one mutant copy that encodes an inactive mitochondrial isoenzyme. A remarkably higher frequency of acute alcohol intoxication among Northeast Asians than among Europeans has been repeatedly shown to be related to the very much reduced activity of the mutant ALDH2-2 isoenzyme.[3] There has been a steady increase over the past 10 years in the number of Japanese alcoholics who manage to overcome their genetically determined aversion to alcoholism from the dominant effects of an ALDH2-2 mutation.[4] This trend demonstrates that, even among those least likely to succumb to alcoholism, there are social pressures to drink.[4]

An activator of ALDH2 enzymatic activity, Alda-1 (N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide), has been shown to reduce ischemia-induced cardiac damage caused by myocardial infarction.[5]

Interactions[edit]

ALDH2 has been shown to interact with GroEL.[6]

See also[edit]

References[edit]

  1. ^ Yoshida A, Ikawa M, Hsu LC, Tani K (1985). "Molecular abnormality and cDNA cloning of human aldehyde dehydrogenases". Alcohol 2 (1): 103–6. doi:10.1016/0741-8329(85)90024-2. PMID 4015823. 
  2. ^ Hsu LC, Tani K, Fujiyoshi T, Kurachi K, Yoshida A (June 1985). "Cloning of cDNAs for human aldehyde dehydrogenases 1 and 2". Proceedings of the National Academy of Sciences of the United States of America 82 (11): 3771–5. doi:10.1073/pnas.82.11.3771. PMC 397869. PMID 2987944. 
  3. ^ a b "Entrez Gene: ALDH2 aldehyde dehydrogenase 2 family (mitochondrial)". 
  4. ^ a b Higuchi S, Matsushita S, Imazeki H, Kinoshita T, Takagi S, Kono H (March 1994). "Aldehyde dehydrogenase genotypes in Japanese alcoholics". Lancet 343 (8899): 741–2. doi:10.1016/S0140-6736(94)91629-2. PMID 7907720. 
  5. ^ Chen C-H, Budas, GR, Churchill EN, Disatnik M-H, Hurley TD, Mochly-Rosen D (September 2008). "Activation of Aldehyde Dehydrogenase-2 Reduces Ischemic Damage to the Heart". Science 321 (5895): 1493–1495. doi:10.1126/science.1158554. PMC 2741612. PMID 18787169. 
  6. ^ Lee KH, Kim HS, Jeong HS, Lee YS (October 2002). "Chaperonin GroESL mediates the protein folding of human liver mitochondrial aldehyde dehydrogenase in Escherichia coli". Biochem. Biophys. Res. Commun. 298 (2): 216–24. doi:10.1016/S0006-291X(02)02423-3. PMID 12387818. 


Further reading[edit]

External links[edit]