5β-Reductase

AKR1D1
Identifiers
Aliases	AKR1D1, 3o5bred, CBAS2, SRD5B1, aldo-keto reductase family 1, member D1, aldo-keto reductase family 1 member D1
External IDs	OMIM: 604741; MGI: 2384785; GeneCards: AKR1D1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3BUR, 3BUV, 3BV7, 3CAQ, 3CAS, 3CAV, 3CMF, 3COT, 3DOP, 3G1R, 3UZW, 3UZX, 3UZY, 3UZZ
Enzyme activity
Gene location (Human)
Chr.	Chromosome 7 (human)
End	138,118,305 bp
Gene location (Mouse)
Chr.	Chromosome 6 (mouse)
End	37,545,750 bp
RNA expression pattern
	Top expressed in
	liver; ; right lobe of liver; ; gonad; ; testicle; ; right testis; ; left testis; ; stromal cell of endometrium; ; lower lobe of lung; ; pancreatic ductal cell; ; epithelium of colon;
	Top expressed in
	left lobe of liver; ; right kidney; ; proximal tubule; ; human kidney; ; sexually immature organism; ; lumbar spinal ganglion; ; lumbar subsegment of spinal cord; ; meninges; ; right ventricle; ; human fetus;
	More reference expression data
	n/a
Gene ontology
Molecular function	delta4-3-oxosteroid 5beta-reductase activity; oxidoreductase activity; steroid binding; aldo-keto reductase (NADP) activity; alditol:NADP+ 1-oxidoreductase activity; alcohol dehydrogenase (NADP+) activity; steroid dehydrogenase activity; ketosteroid monooxygenase activity;
Cellular component	cytoplasm; cytosol;
Biological process	lipid catabolic process; digestion; bile acid catabolic process; steroid metabolic process; bile acid biosynthetic process; cholesterol catabolic process; androgen metabolic process; lipid metabolism; C21-steroid hormone metabolic process;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	6718
	208665
	ENSG00000122787
	ENSMUSG00000038641
	P51857
	Q8VCX1
	NM_005989; NM_001190906; NM_001190907
	NM_145364
	NP_001177835; NP_001177836; NP_005980
	NP_663339
	Wikidata
View/Edit Human	View/Edit Mouse

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PMC	articles
PubMed	articles
NCBI	proteins

Δ⁴-3-Oxosteroid 5β-reductase
Δ4-3-Oxosteroid 5β-reductase
Identifiers
EC no.	1.3.1.3
CAS no.	2604034
Databases
BRENDA	enzyme data
ExPASy	NiceZyme view
KEGG	enzyme entry
MetaCyc	metabolic pathway
Rhea	reactions
PDB structures	RCSB PDB PDBe PDBsum
PMC
Search
PMC	articles
PubMed	articles
NCBI	proteins

5β-Reductase, also called Δ⁴-3-oxosteroid 5β-reductase (EC 1.3.1.3), is an enzyme that in humans is encoded by the gene AKC1D1. Its systematic name is 5β-cholestan-3-one:NADP⁺ 4,5-oxidoreductase.^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]

This enzyme catalyses the following general chemical reaction:

5β-cholestan-3-one + NADP⁺

\rightleftharpoons

cholest-4-en-3-one + NADPH + H⁺

For example, it interconverts 5β-dihydrocortisone and cortisone:^[9]^[10]

dihydrocortisone

+ NADP⁺

H⁺

Reversible left-right reaction arrow with minor forward product(s) to top right and minor reverse substrate(s) from bottom right

H⁺

cortisone

+ NADPH

AKR1D1

Aldo-keto reductase family 1 member D1 (AKR1D1), the sole 5β-Reductase isozyme known in humans,^[15] is an enzyme which is humans is encoded by the gene AKR1D1. This enzyme is important for bile acid synthesis and steroid metabolism.^[16]

AKR1D1 efficiently acts on bile-acid intermediates, progesterone, 17α-hydroxyprogesterone, androstenedione, and testosterone to transform them into 5β-reduced metabolites. It can also act on aldosterone, corticosterone, and cortisol.^[9]

Medical significance

Pathogenic mutations in AKR1D1 are associated with a rare type of bile acid synthesis disorder called congenital bile acid synthesis defect 2 (CBAS2).^[17]^[16]

Other names

This enzyme has multiple alternative names, including: 3-oxo-Δ⁴-steroid 5β-reductase, androstenedione 5β-reductase, cholestenone 5β-reductase, cortisone 5β-reductase, cortisone Δ⁴-5β-reductase, steroid 5β-reductase, testosterone 5β-reductase, Δ⁴-3-ketosteroid 5β-reductase, Δ⁴-5β-reductase, Δ⁴-hydrogenase, 4,5β-dihydrocortisone:NADP⁺ Δ⁴-oxidoreductase, and 3-oxo-5β-steroid:NADP⁺ Δ⁴-oxidoreductase.

References

↑ Dorfman RI, Forchielli E (November 1956). "Separation of delta 4-5 alpha-hydrogenases from rat liver homogenates". The Journal of Biological Chemistry. 223 (1): 443–8. doi:10.1016/S0021-9258(18)65153-1. PMID 13376613.
↑ Brown-Grant K, Forchielli E, Dorfman RI (May 1960). "The delta4-hydrogenases of guinea pig adrenal gland". The Journal of Biological Chemistry. 235 (5): 1317–20. doi:10.1016/S0021-9258(18)69405-0. PMID 13805063.
↑ Levy, H.R. & Talalay, P. (1957). "Enzymatic introduction of double bonds into steroid ring A". J. Am. Chem. Soc. 79 (10): 2658–2659. Bibcode:1957JAChS..79.2658L. doi:10.1021/ja01567a089.
↑ Tomkins GM (March 1957). "The enzymatic reduction of delta 4-3-ketosteroids". The Journal of Biological Chemistry. 225 (1): 13–24. doi:10.1016/S0021-9258(18)64906-3. PMID 13416214.
↑ Sugimoto Y, Yoshida M, Tamaoki B (December 1990). "Purification of 5 beta-reductase from hepatic cytosol fraction of chicken". The Journal of Steroid Biochemistry and Molecular Biology. 37 (5): 717–24. doi:10.1016/0960-0760(90)90356-p. PMID 2278855. S2CID 54431282.
↑ Okuda A, Okuda K (June 1984). "Purification and characterization of delta 4-3-ketosteroid 5 beta-reductase". The Journal of Biological Chemistry. 259 (12): 7519–24. doi:10.1016/S0021-9258(17)42821-3. PMID 6736016.
↑ Charbonneau A, The VL (January 2001). "Genomic organization of a human 5beta-reductase and its pseudogene and substrate selectivity of the expressed enzyme". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1517 (2): 228–35. doi:10.1016/s0167-4781(00)00278-5. PMID 11342103.
↑ Kondo KH, Kai MH, Setoguchi Y, Eggertsen G, Sjöblom P, Setoguchi T, Okuda KI, Björkhem I (January 1994). "Cloning and expression of cDNA of human delta 4-3-oxosteroid 5 beta-reductase and substrate specificity of the expressed enzyme". European Journal of Biochemistry. 219 (1–2): 357–63. doi:10.1111/j.1432-1033.1994.tb19947.x. PMID 7508385.
1 2 Enzyme 1.3.1.3 at KEGG Pathway Database.
↑ Furuebisu M, Deguchi S, Okuda K (March 1987). "Identification of cortisone 5 beta-reductase as delta 4-3-ketosteroid 5 beta-reductase". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 912 (1): 110–4. doi:10.1016/0167-4838(87)90253-6. PMID 3828348.
1 2 3 GRCh38: Ensembl release 89: ENSG00000122787 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000038641 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ EC 1.3.1.3
1 2 "Aldo-keto reductase family 1 member D1". uniprot.org. UniProt consortium. Retrieved 2026-09-14.
↑ "BILE ACID SYNTHESIS DEFECT, CONGENITAL, 2; CBAS2". Online Mendelian Inheritance in Man. Johns Hopkins University. Retrieved 2026-09-14.

External links

Delta4-3-oxosteroid+5beta-reductase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

[1] Dorfman RI, Forchielli E (November 1956). "Separation of delta 4-5 alpha-hydrogenases from rat liver homogenates". The Journal of Biological Chemistry. 223 (1): 443–8. doi:10.1016/S0021-9258(18)65153-1. PMID 13376613.

[2] Brown-Grant K, Forchielli E, Dorfman RI (May 1960). "The delta4-hydrogenases of guinea pig adrenal gland". The Journal of Biological Chemistry. 235 (5): 1317–20. doi:10.1016/S0021-9258(18)69405-0. PMID 13805063.

[3] Levy, H.R. & Talalay, P. (1957). "Enzymatic introduction of double bonds into steroid ring A". J. Am. Chem. Soc. 79 (10): 2658–2659. Bibcode:1957JAChS..79.2658L. doi:10.1021/ja01567a089.

[4] Tomkins GM (March 1957). "The enzymatic reduction of delta 4-3-ketosteroids". The Journal of Biological Chemistry. 225 (1): 13–24. doi:10.1016/S0021-9258(18)64906-3. PMID 13416214.

[5] Sugimoto Y, Yoshida M, Tamaoki B (December 1990). "Purification of 5 beta-reductase from hepatic cytosol fraction of chicken". The Journal of Steroid Biochemistry and Molecular Biology. 37 (5): 717–24. doi:10.1016/0960-0760(90)90356-p. PMID 2278855. S2CID 54431282.

[6] Okuda A, Okuda K (June 1984). "Purification and characterization of delta 4-3-ketosteroid 5 beta-reductase". The Journal of Biological Chemistry. 259 (12): 7519–24. doi:10.1016/S0021-9258(17)42821-3. PMID 6736016.

[7] Charbonneau A, The VL (January 2001). "Genomic organization of a human 5beta-reductase and its pseudogene and substrate selectivity of the expressed enzyme". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1517 (2): 228–35. doi:10.1016/s0167-4781(00)00278-5. PMID 11342103.

[8] Kondo KH, Kai MH, Setoguchi Y, Eggertsen G, Sjöblom P, Setoguchi T, Okuda KI, Björkhem I (January 1994). "Cloning and expression of cDNA of human delta 4-3-oxosteroid 5 beta-reductase and substrate specificity of the expressed enzyme". European Journal of Biochemistry. 219 (1–2): 357–63. doi:10.1111/j.1432-1033.1994.tb19947.x. PMID 7508385.

[KEGG-9] 1 2 Enzyme 1.3.1.3 at KEGG Pathway Database.

[10] Furuebisu M, Deguchi S, Okuda K (March 1987). "Identification of cortisone 5 beta-reductase as delta 4-3-ketosteroid 5 beta-reductase". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 912 (1): 110–4. doi:10.1016/0167-4838(87)90253-6. PMID 3828348.

[refGRCh38Ensembl-11] 1 2 3 GRCh38: Ensembl release 89: ENSG00000122787 – Ensembl, May 2017

[refGRCm38Ensembl-12] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000038641 – Ensembl, May 2017

[13] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[14] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[15] EC 1.3.1.3

[uniprot-16] 1 2 "Aldo-keto reductase family 1 member D1". uniprot.org. UniProt consortium. Retrieved 2026-09-14.

[17] "BILE ACID SYNTHESIS DEFECT, CONGENITAL, 2; CBAS2". Online Mendelian Inheritance in Man. Johns Hopkins University. Retrieved 2026-09-14.

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v t e Oxidoreductases: CH–CH oxidoreductases (EC 1.3)
1.3.1: NAD/NADP acceptor	Enoyl-acyl carrier protein reductase/Enoyl ACP reductase 7-Dehydrocholesterol reductase Biliverdin reductase 2,4 Dienoyl-CoA reductase Dihydroxymethyloxo-tetrahydroquinoline dehydrogenase
1.3.3: Oxygen acceptor	Dihydroorotate dehydrogenase Coproporphyrinogen III oxidase Protoporphyrinogen oxidase Bilirubin oxidase Acyl-CoA oxidase Dihydrouracil oxidase Tetrahydroberberine oxidase Secologanin synthase Tryptophan alpha,beta-oxidase Pyrroloquinoline-quinone synthase L-galactonolactone oxidase
1.3.5: Quinone	Succinate dehydrogenase SDHA SDHB SDHC SDHD
1.3.99: Other acceptors	Fumarate reductase Butyryl-CoA dehydrogenase Acyl CoA dehydrogenase ACADSB ACADS 5α-reductase SRD5A1 SRD5A2 SRD5A3 Glutaryl-CoA dehydrogenase Isovaleryl coenzyme A dehydrogenase 3-oxo-5beta-steroid 4-dehydrogenase

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

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