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MetaCyc Enzyme: retinal dehydrogenase 1

Gene: ALDH1A1 Accession Number: HS09183 (MetaCyc)

Synonyms: ALDC, ALDH1, PUMB1, aldehyde dehydrogenase family 1 member A1, cytosolic aldehyde dehydrogenase, ALDH-E1, ALHDII, RALDH 1, RalDH1

Species: Homo sapiens

Summary:
Retinal dehydrogenase 1 can bind both free retinal and RBP1-bound retinal and oxidize it into retinoate.

The enzyme was originally known as the cytosolic isozyme of liver aldehyde dehydrogenase [Hempel84, Abriola87]. However, characterization of the enzyme's activity showed that it exhibits strong activity for oxidation of retinal to retinoic acid, with the catalytic efficiency (Vmax/Km) about 600 times higher than that for acetaldehyde [Yoshida92a, Yoshida93b]. Thus, the enzyme was renamed retinal dehydrogenase 1. ALDH1A1 enzyme purified from rat recognizes RBP1-bound retinal as substrate (with Km = 0.8 μM) and is inhibited by apo-CRBP1 with an IC50 of 1.4 μM [Penzes97].

The human gene, which is located on q21 of chromosome 9, has been cloned and its structure analyzed [Hsu86, Raghunathan88, Hsu89]. cDNAs encoding the enzyme were cloned and expressed in Escherichia coli [Hsu85, Zheng93].

Locations: cytoplasm, cytosol

Map Position: [67,372,137 <- 67,424,511]

Molecular Weight of Polypeptide: 54.862 kD (from nucleotide sequence), 55.0 kD (experimental) [Zheng93 ]

pI: 5.4 [Zheng93]

Unification Links: ArrayExpress:P00352 , Entrez-gene:216 , Mint:MINT-4999613 , PhosphoSite:P00352 , PhylomeDB:P00352 , Pride:P00352 , Protein Model Portal:P00352 , SMR:P00352 , String:9606.ENSP00000297785 , UniProt:P00352

Relationship Links: InterPro:IN-FAMILY:IPR015590 , InterPro:IN-FAMILY:IPR016160 , InterPro:IN-FAMILY:IPR016161 , InterPro:IN-FAMILY:IPR016162 , InterPro:IN-FAMILY:IPR016163 , InterPro:IN-FAMILY:IPR029510 , Pfam:IN-FAMILY:PF00171 , Prosite:IN-FAMILY:PS00070 , Prosite:IN-FAMILY:PS00687

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Instance reaction of [an aldehyde + NAD+ + H2O → a carboxylate + NADH + 2 H+] (1.2.1.3):
i1: all-trans-retinal + NAD+ + H2O = all-trans-retinoate + NADH + 2 H+ (1.2.1.36)

GO Terms:

Biological Process: GO:0006081 - cellular aldehyde metabolic process
Molecular Function: GO:0004029 - aldehyde dehydrogenase (NAD) activity
GO:0005497 - androgen binding
GO:0016491 - oxidoreductase activity
Cellular Component: GO:0005737 - cytoplasm
GO:0005829 - cytosol


Enzymatic reaction of: all-trans-retinal dehydrogenase (retinal dehydrogenase 1)

EC Number: 1.2.1.36

an all-trans retinal-[cellular-retinol-binding-protein] + NAD+ + H2O <=> all-trans-retinoate + a cellular-retinol-binding protein + NADH + 2 H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: retinoate biosynthesis I

Kinetic Parameters:

Substrate
Km (μM)
Citations
an all-trans retinal-[cellular-retinol-binding-protein]
0.06
[Yoshida92a]


Enzymatic reaction of: all-trans-retinal dehydrogenase (retinal dehydrogenase 1)

EC Number: 1.2.1.36

all-trans-retinal + NAD+ + H2O <=> all-trans-retinoate + NADH + 2 H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.

Exons/Introns:

Schematic showing introns, exons and/or isoforms of ALDH1A1


References

Abriola87: Abriola DP, Fields R, Stein S, MacKerell AD, Pietruszko R (1987). "Active site of human liver aldehyde dehydrogenase." Biochemistry 26(18);5679-84. PMID: 3676276

Cowan93: Cowan SW, Newcomer ME, Jones TA (1993). "Crystallographic studies on a family of cellular lipophilic transport proteins. Refinement of P2 myelin protein and the structure determination and refinement of cellular retinol-binding protein in complex with all-trans-retinol." J Mol Biol 230(4);1225-46. PMID: 7683727

Hempel84: Hempel J, von Bahr-Lindstrom H, Jornvall H (1984). "Aldehyde dehydrogenase from human liver. Primary structure of the cytoplasmic isoenzyme." Eur J Biochem 141(1);21-35. PMID: 6723659

Hsu85: Hsu LC, Tani K, Fujiyoshi T, Kurachi K, Yoshida A (1985). "Cloning of cDNAs for human aldehyde dehydrogenases 1 and 2." Proc Natl Acad Sci U S A 82(11);3771-5. PMID: 2987944

Hsu86: Hsu LC, Yoshida A, Mohandas T (1986). "Chromosomal assignment of the genes for human aldehyde dehydrogenase-1 and aldehyde dehydrogenase-2." Am J Hum Genet 38(5);641-8. PMID: 3013004

Hsu89: Hsu LC, Chang WC, Yoshida A (1989). "Genomic structure of the human cytosolic aldehyde dehydrogenase gene." Genomics 5(4);857-65. PMID: 2591967

Li96a: Li E, Norris AW (1996). "Structure/function of cytoplasmic vitamin A-binding proteins." Annu Rev Nutr 16;205-34. PMID: 8839926

Newcomer98: Newcomer ME, Jamison RS, Ong DE (1998). "Structure and function of retinoid-binding proteins." Subcell Biochem 30;53-80. PMID: 9932510

Penzes97: Penzes P, Wang X, Napoli JL (1997). "Enzymatic characteristics of retinal dehydrogenase type I expressed in Escherichia coli." Biochim Biophys Acta 1342(2);175-81. PMID: 9392526

Raghunathan88: Raghunathan L, Hsu LC, Klisak I, Sparkes RS, Yoshida A, Mohandas T (1988). "Regional localization of the human genes for aldehyde dehydrogenase-1 and aldehyde dehydrogenase-2." Genomics 2(3);267-9. PMID: 3397064

Winter93: Winter NS, Bratt JM, Banaszak LJ (1993). "Crystal structures of holo and apo-cellular retinol-binding protein II." J Mol Biol 230(4);1247-59. PMID: 8487303

Yoshida92a: Yoshida A, Hsu LC, Dave V (1992). "Retinal oxidation activity and biological role of human cytosolic aldehyde dehydrogenase." Enzyme 46(4-5);239-44. PMID: 1292933

Yoshida93b: Yoshida A, Hsu LC, Yanagawa Y (1993). "Biological role of human cytosolic aldehyde dehydrogenase 1: hormonal response, retinal oxidation and implication in testicular feminization." Adv Exp Med Biol 328;37-44. PMID: 8493914

Zheng93: Zheng CF, Wang TT, Weiner H (1993). "Cloning and expression of the full-length cDNAS encoding human liver class 1 and class 2 aldehyde dehydrogenase." Alcohol Clin Exp Res 17(4);828-31. PMID: 8214422


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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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