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MetaCyc Enzyme: retinol dehydrogenase 9

Gene: DHRS9 Accession Numbers: HS01113 (MetaCyc), UNQ835/PRO1773

Synonyms: 3-α hydroxysteroid dehydrogenase, NADP-dependent retinol dehydrogenase/reductase, RDH-E2, RDHL, short-chain dehydrogenase/reductase retSDR8, dehydrogenase/reductase SDR family member 9

Species: Homo sapiens

Summary:
General Background

The key enzymes involved in retinoid metabolisms are alcohol and aldehyde dehydrogenases that convert retinols to aldehydes and aldehydes to carboxylic acids, respectively. The first oxidation reaction is catalyzed by a large number of enzymes from the small-chain dehydrogenase/reductase (SDR) superfamily and by classic medium chain alcohol dehydrogenases. SDRs are weakly conserved in their primary sequences, with the exception of key residues involved in catalysis, nucleotide recognition, and members of closely related subfamilies. SDRs also display NADP or NAD cofactor preference and, if they are retinol dehydrogenases (RDHs), favor all-trans- or cis-retinol substrates. Some RDH enzymes also catalyze the oxidation of steroids in addition to retinols [Haeseleer02].

About This Enzyme

This enzyme is a member of the short-chain dehydrogenase/reductase (SDR) family. It has 3-α-hydroxysteroid dehydrogenase activity, and was shown to convert allopregnanolone to 5-α-pregnane-3,20-dione and 5-α-androstan-3α,17β-diol to 5-α-dihydrotestosterone [Chetyrkin01].

In addition, the enzyme may play a role in the biosynthesis of retinoic acid. The enzyme is abundantly expressed in the epidermis, epidermal appendages and in cultured epidermal keratinocytes, and was shown to function as a bona fide retinol dehydrogenase in liver keratinocytes and in isolated keratinocyte microsomes [Markova03]. Its expression is up-regulated by retinoids [Soref01] The enzyme recognizes both free- and CRBP-bound retinol, and shows preference toward NADP as a co-substrate. The authors suggested that DHRS9 is the major microsomal retinol dehydrogenase in the epidermal keratinocytes [Markova03].

Map Position: [168,462,964 -> 168,494,342]

Molecular Weight of Polypeptide: 35.227 kD (from nucleotide sequence)

Unification Links: ArrayExpress:Q9BPW9 , Entrez-gene:10170 , MOPED:Q9BPW9 , UniProt:Q9BPW9

Gene-Reaction Schematic: ?

Instance reactions of [allopregnanolone + NAD(P)+ ↔ 5-α-pregnane-3,20-dione + NAD(P)H + H+] (1.1.1.213):
i1: allopregnanolone + NAD+ → 5-α-pregnane-3,20-dione + NADH + H+ (1.1.-.-)

i2: allopregnanolone + NADP+ ← 5-α-pregnane-3,20-dione + NADPH + H+ (1.1.1.278)

GO Terms:

Biological Process: GO:0008152 - metabolic process
Molecular Function: GO:0016491 - oxidoreductase activity

Credits:
Created 20-Aug-2011 by Caspi R , SRI International


Enzymatic reaction of: 3α-hydroxysteroid dehydrogenase (retinol dehydrogenase 9)

EC Number: 1.1.-.-

allopregnanolone + NAD+ <=> 5-α-pregnane-3,20-dione + NADH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

Credits:
Imported from HumanCyc 15-May-2014 by Montanucci L , Universitat Pompeu Fabra Barcelona


Enzymatic reaction of: retinol dehydrogenase 9

EC Number: 1.1.1.-

choloyl-CoA + NAD(P)+ <=> 3-oxo-cholyl-CoA + NAD(P)H + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

This reaction is reversible.

Credits:
Imported from HumanCyc 15-May-2014 by Montanucci L , Universitat Pompeu Fabra Barcelona


Enzymatic reaction of: retinol dehydrogenase 9

EC Number: 1.1.1.-

cholate + NAD+ <=> 3-dehydrocholate + NADH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

This reaction is reversible.

Credits:
Imported from HumanCyc 15-May-2014 by Montanucci L , Universitat Pompeu Fabra Barcelona


Enzymatic reaction of: 3α-hydroxysteroid dehydrogenase (retinol dehydrogenase 9)

5-α-androstan-3α,17β-diol + NAD(P)+ <=> 5-α-dihydrotestosterone + NAD(P)H + 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.


Enzymatic reaction of: all-trans-retinol dehydrogenase (retinol dehydrogenase 9)

EC Number: 1.1.1.300

all-trans-retinol + NADP+ <=> all-trans-retinal + NADPH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

This reaction is reversible.

In Pathways: the visual cycle I (vertebrates) , retinol biosynthesis

Exons/Introns:


References

Chetyrkin01: Chetyrkin SV, Belyaeva OV, Gough WH, Kedishvili NY (2001). "Characterization of a novel type of human microsomal 3alpha -hydroxysteroid dehydrogenase: unique tissue distribution and catalytic properties." J Biol Chem 276(25);22278-86. PMID: 11294878

Haeseleer02: Haeseleer F, Jang GF, Imanishi Y, Driessen CA, Matsumura M, Nelson PS, Palczewski K (2002). "Dual-substrate specificity short chain retinol dehydrogenases from the vertebrate retina." J Biol Chem 277(47);45537-46. PMID: 12226107

Markova03: Markova NG, Pinkas-Sarafova A, Karaman-Jurukovska N, Jurukovski V, Simon M (2003). "Expression pattern and biochemical characteristics of a major epidermal retinol dehydrogenase." Mol Genet Metab 78(2);119-35. PMID: 12618084

Soref01: Soref CM, Di YP, Hayden L, Zhao YH, Satre MA, Wu R (2001). "Characterization of a novel airway epithelial cell-specific short chain alcohol dehydrogenase/reductase gene whose expression is up-regulated by retinoids and is involved in the metabolism of retinol." J Biol Chem 276(26);24194-202. PMID: 11304534


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sun Nov 23, 2014, BIOCYC13B.