ALDH1A1 explained

Aldehyde dehydrogenase 1 family, member A1, also known as ALDH1A1 or retinaldehyde dehydrogenase 1 (RALDH1), is an enzyme that is encoded by the ALDH1A1 gene.^{[1] [2]}

Function

This protein belongs to the aldehyde dehydrogenases family of proteins. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. Two major liver isoforms of this enzyme, cytosolic and mitochondrial, can be distinguished by their electrophoretic mobilities, kinetic properties, and subcellular localizations; this gene encodes the main cytosolic isoform, which has a lower affinity for aldehydes than the mitochondrial enzyme.^[3] Most Caucasians have two major isozymes, while approximately 50% of East Asians have only the cytosolic isozyme, missing the mitochondrial isozyme. A remarkably higher frequency of acute alcohol intoxication among East Asians than among Caucasians could be related to the absence of the mitochondrial isozyme. Furthermore, mutations in this enzyme have been linked to alcoholism in humans.^{[4] [5]}

ALDH1A1 also belongs to the group of corneal crystallins that help maintain the transparency of the cornea.^[6] ALDH1A1 maintains stemness of cancer cells and several drugs have been designed to target cancer stem cells by targeting ALDH1A1.^[7]

Further reading

• Walsh N, Dowling P, O'Donovan N, Henry M, Meleady P, Clynes M . Aldehyde dehydrogenase 1A1 and gelsolin identified as novel invasion-modulating factors in conditioned medium of pancreatic cancer cells . Journal of Proteomics . 71 . 5 . 561–71 . December 2008 . 18848913 . 10.1016/j.jprot.2008.09.002 .
• Barley K, Dracheva S, Byne W . Subcortical oligodendrocyte- and astrocyte-associated gene expression in subjects with schizophrenia, major depression and bipolar disorder . Schizophrenia Research . 112 . 1–3 . 54–64 . July 2009 . 19447584 . 10.1016/j.schres.2009.04.019 . 39003080 .
• Ekhart C, Doodeman VD, Rodenhuis S, Smits PH, Beijnen JH, Huitema AD . Influence of polymorphisms of drug metabolizing enzymes (CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, GSTA1, GSTP1, ALDH1A1 and ALDH3A1) on the pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide . Pharmacogenetics and Genomics . 18 . 6 . 515–23 . June 2008 . 18496131 . 10.1097/FPC.0b013e3282fc9766 . 5604777 .
• Rodriguez FJ, Giannini C, Asmann YW, Sharma MK, Perry A, Tibbetts KM, Jenkins RB, Scheithauer BW, Anant S, Jenkins S, Eberhart CG, Sarkaria JN, Gutmann DH . 6 . Gene expression profiling of NF-1-associated and sporadic pilocytic astrocytoma identifies aldehyde dehydrogenase 1 family member L1 (ALDH1L1) as an underexpressed candidate biomarker in aggressive subtypes . Journal of Neuropathology and Experimental Neurology . 67 . 12 . 1194–204 . December 2008 . 19018242 . 2730602 . 10.1097/NEN.0b013e31818fbe1e .
• Carpentino JE, Hynes MJ, Appelman HD, Zheng T, Steindler DA, Scott EW, Huang EH . Aldehyde dehydrogenase-expressing colon stem cells contribute to tumorigenesis in the transition from colitis to cancer . Cancer Research . 69 . 20 . 8208–15 . October 2009 . 19808966 . 2776663 . 10.1158/0008-5472.CAN-09-1132 .
• Ma S, Chan KW, Lee TK, Tang KH, Wo JY, Zheng BJ, Guan XY . Aldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populations . Molecular Cancer Research . 6 . 7 . 1146–53 . July 2008 . 18644979 . 10.1158/1541-7786.MCR-08-0035 . free .
• Xiao T, Shoeb M, Siddiqui MS, Zhang M, Ramana KV, Srivastava SK, Vasiliou V, Ansari NH . 6 . Molecular cloning and oxidative modification of human lens ALDH1A1: implication in impaired detoxification of lipid aldehydes . Journal of Toxicology and Environmental Health. Part A . 72 . 9 . 577–84 . 2009 . 19296407 . 5645793 . 10.1080/15287390802706371 . 2009JTEHA..72..577X .
• Cañestro C, Catchen JM, Rodríguez-Marí A, Yokoi H, Postlethwait JH . Consequences of lineage-specific gene loss on functional evolution of surviving paralogs: ALDH1A and retinoic acid signaling in vertebrate genomes . PLOS Genetics . 5 . 5 . e1000496 . May 2009 . 19478994 . 2682703 . 10.1371/journal.pgen.1000496 . Gojobori . Takashi . free .
• Saito A, Kawamoto M, Kamatani N . Association study between single-nucleotide polymorphisms in 199 drug-related genes and commonly measured quantitative traits of 752 healthy Japanese subjects . Journal of Human Genetics . 54 . 6 . 317–23 . June 2009 . 19343046 . 10.1038/jhg.2009.31 . free .
• Chen YC, Chen YW, Hsu HS, Tseng LM, Huang PI, Lu KH, Chen DT, Tai LK, Yung MC, Chang SC, Ku HH, Chiou SH, Lo WL . 6 . Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer . Biochemical and Biophysical Research Communications . 385 . 3 . 307–13 . July 2009 . 19450560 . 10.1016/j.bbrc.2009.05.048 .
• Tabakoff B, Saba L, Printz M, Flodman P, Hodgkinson C, Goldman D, Koob G, Richardson HN, Kechris K, Bell RL, Hübner N, Heinig M, Pravenec M, Mangion J, Legault L, Dongier M, Conigrave KM, Whitfield JB, Saunders J, Grant B, Hoffman PL . 6 . Genetical genomic determinants of alcohol consumption in rats and humans . BMC Biology . 7 . 70 . October 2009 . 19874574 . 2777866 . 10.1186/1741-7007-7-70 . free .
• Morimoto K, Kim SJ, Tanei T, Shimazu K, Tanji Y, Taguchi T, Tamaki Y, Terada N, Noguchi S . 6 . Stem cell marker aldehyde dehydrogenase 1-positive breast cancers are characterized by negative estrogen receptor, positive human epidermal growth factor receptor type 2, and high Ki67 expression . Cancer Science . 100 . 6 . 1062–8 . June 2009 . 19385968 . 10.1111/j.1349-7006.2009.01151.x . 22510108 . free . 11158415 .
• Ekhart C, Rodenhuis S, Smits PH, Beijnen JH, Huitema AD . Relations between polymorphisms in drug-metabolising enzymes and toxicity of chemotherapy with cyclophosphamide, thiotepa and carboplatin . Pharmacogenetics and Genomics . 18 . 11 . 1009–15 . November 2008 . 18854779 . 10.1097/FPC.0b013e328313aaa4 . 2979088 .
• Wan C, Shi Y, Zhao X, Tang W, Zhang M, Ji B, Zhu H, Xu Y, Li H, Feng G, He L . 6 . Positive association between ALDH1A2 and schizophrenia in the Chinese population . Progress in Neuro-Psychopharmacology & Biological Psychiatry . 33 . 8 . 1491–5 . November 2009 . 19703508 . 10.1016/j.pnpbp.2009.08.008 . 32862839 .
• Low SK, Kiyotani K, Mushiroda T, Daigo Y, Nakamura Y, Zembutsu H . Association study of genetic polymorphism in ABCC4 with cyclophosphamide-induced adverse drug reactions in breast cancer patients . Journal of Human Genetics . 54 . 10 . 564–71 . October 2009 . 19696793 . 10.1038/jhg.2009.79 . free .
• Moore SM, Liang T, Graves TJ, McCall KM, Carr LG, Ehlers CL . Identification of a novel cytosolic aldehyde dehydrogenase allele, ALDH1A1*4 . Human Genomics . 3 . 4 . 304–7 . July 2009 . 19706361 . 2885287 . 10.1186/1479-7364-3-4-304 . free .
• Chang B, Liu G, Xue F, Rosen DG, Xiao L, Wang X, Liu J . ALDH1 expression correlates with favorable prognosis in ovarian cancers . Modern Pathology . 22 . 6 . 817–23 . June 2009 . 19329942 . 2692456 . 10.1038/modpathol.2009.35 .
• Lind PA, Eriksson CJ, Wilhelmsen KC . The role of aldehyde dehydrogenase-1 (ALDH1A1) polymorphisms in harmful alcohol consumption in a Finnish population . Human Genomics . 3 . 1 . 24–35 . September 2008 . 19129088 . 3525184 . 10.1186/1479-7364-3-1-24 . free .
• Moreb JS, Baker HV, Chang LJ, Amaya M, Lopez MC, Ostmark B, Chou W . ALDH isozymes downregulation affects cell growth, cell motility and gene expression in lung cancer cells . Molecular Cancer . 7 . 1 . 87 . November 2008 . 19025616 . 2605459 . 10.1186/1476-4598-7-87 . free .
• Dancik GM, Varisli L, Vlahopoulos SA . The Molecular Context of Oxidant Stress Response in Cancer Establishes ALDH1A1 as a Critical Target: What This Means for Acute Myeloid Leukemia. . International Journal of Molecular Sciences . 2023 . 24 . 11 . 9372 . 10.3390/ijms24119372 . 37298333 . 10253856 . free .

Notes and References

1. Pereira F, Rosenmann E, Nylen E, Kaufman M, Pinsky L, Wrogemann K . The 56 kDa androgen binding protein is an aldehyde dehydrogenase . Biochemical and Biophysical Research Communications . 175 . 3 . 831–8 . March 1991 . 1709013 . 10.1016/0006-291X(91)91640-X .
2. Hsu LC, Tani K, Fujiyoshi T, Kurachi K, Yoshida A . 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 . June 1985 . 2987944 . 397869 . 10.1073/pnas.82.11.3771 . 1985PNAS...82.3771H . free .
3. Web site: Entrez Gene: ALDH1A1.
4. Sherva R, Rice JP, Neuman RJ, Rochberg N, Saccone NL, Bierut LJ . Associations and interactions between SNPs in the alcohol metabolizing genes and alcoholism phenotypes in European Americans . Alcoholism: Clinical and Experimental Research . 33 . 5 . 848–57 . May 2009 . 19298322 . 2892966 . 10.1111/j.1530-0277.2009.00904.x .
5. Liu J, Zhou Z, Hodgkinson CA, Yuan Q, Shen PH, Mulligan CJ, Wang A, Gray RR, Roy A, Virkkunen M, Goldman D, Enoch MA . 6 . Haplotype-based study of the association of alcohol-metabolizing genes with alcohol dependence in four independent populations . Alcoholism: Clinical and Experimental Research . 35 . 2 . 304–16 . February 2011 . 21083667 . 3026908 . 10.1111/j.1530-0277.2010.01346.x .
6. Jester JV, Moller-Pedersen T, Huang J, Sax CM, Kays WT, Cavangh HD, Petroll WM, Piatigorsky J . 6 . The cellular basis of corneal transparency: evidence for 'corneal crystallins' . Journal of Cell Science . 112 . 5 . 613–22 . March 1999 . 9973596 . 10.1242/jcs.112.5.613 . 112 .
7. Muralikrishnan V, Hurley TD, Nephew KP . Targeting Aldehyde Dehydrogenases to Eliminate Cancer Stem Cells in Gynecologic Malignancies . Cancers . 12 . 4 . April 2020 . 961 . 32295073 . 10.3390/cancers12040961 . 7225959 . free .