Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DER0XCH)

• DME Name: Farnesol dehydrogenase (AKR1B15)
• Synonyms: Aldo-keto reductase family 1 member B15; Testosterone 17beta-dehydrogenase; Estradiol 17-beta-dehydrogenase AKR1B15; AKR1B15
• Gene Name: AKR1B15
• UniProt ID: AK1BF_HUMAN
• INTEDE ID: DME0399
• Gene ID: 441282
• EC Number:
  EC: 1.1.1.54
  Oxidoreductase
  CH-OH donor oxidoreductase
  NAD/NADP oxidoreductase
  EC: 1.1.1.54
• Lineage:
  Species: Homo sapiens
  Kingdom: Metazoa
  Phylum: Chordata
  Class: Mammalia
  Order: Primates
  Family: Hominidae
  Genus: Homo
  Species: Homo sapiens
• Sequence:
  MATFVELSTKAKMPIVGLGTWRSLLGKVKEAVKVAIDAEYRHIDCAYFYENQHEVGEAIQ
  EKIQEKAVMREDLFIVSKVWPTFFERPLVRKAFEKTLKDLKLSYLDVYLIHWPQGFKTGD
  DFFPKDDKGNMISGKGTFLDAWEAMEELVDEGLVKALGVSNFNHFQIERLLNKPGLKYKP
  VTNQVECHPYLTQEKLIQYCHSKGITVTAYSPLGSPDRPWAKPEDPSLLEDPKIKEIAAK
  HKKTTAQVLIRFHIQRNVTVIPKSMTPAHIVENIQVFDFKLSDEEMATILSFNRNWRAFD
  FKEFSHLEDFPFDAEY
• Function: This enzyme catalyzes the NADPH-dependent reduction of a variety of carbonyl substrates, like aromatic aldehydes, alkenals, ketones and alpha-dicarbonyl compounds. In addition, it catalyzes the reduction of androgens and estrogens with high positional selectivity (shows 17-beta- hydroxysteroid dehydrogenase activity) as well as 3-keto-acyl-CoAs. It displays strong enzymatic activity toward all-trans- retinal and 9-cis-retinal and may play a physiological role in retinoid metabolism.
• Reactome Pathway: Estrogen biosynthesis (R-HSA-193144)

Molecular Interaction Atlas (MIA) of This DME

3 Approved Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[1]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[1]
Testosterone cypionate	DMC1TEV	N. A.	N. A.	Approved	[1]

1 Clinical Trial Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ANDROSTERONE	DMITJAK	N. A.	N. A.	Phase 3	[1]

1 Investigative Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nitrobenzaldehyde	DM4UHB5	N. A.	N. A.	Investigative	[2]

Experimental Enzyme Kinetic Data of Drugs

Drug Name	Indication	Highest Status	Kinetic Data	REF
ANDROSTERONE	N. A.	Phase 3	Km = 0.0028 microM	[1]
Estradiol	Acne vulgaris [ED80]	Approved	Km = 0.0091 microM	[1]
Estrone	Acne vulgaris [ED80]	Approved	Km = 0.0035 microM	[1]

References

• [1] Aldo-keto Reductase 1B15 (AKR1B15): a mitochondrial human aldo-keto reductase with activity toward steroids and 3-keto-acyl-CoA conjugates. J Biol Chem. 2015 Mar 6;290(10):6531-45.
• [2] Functional expression of novel human and murine AKR1B genes. Chem Biol Interact. 2011 May 30;191(1-3):177-84.