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Class of enzymes From Wikipedia, the free encyclopedia
17β-Hydroxysteroid dehydrogenases (17β-HSD, HSD17B) (EC 1.1.1.51), also 17-ketosteroid reductases (17-KSR), are a group of alcohol oxidoreductases which catalyze the reduction of 17-ketosteroids and the dehydrogenation of 17β-hydroxysteroids in steroidogenesis and steroid metabolism.[1][2][3][4][5] This includes interconversion of DHEA and androstenediol, androstenedione and testosterone, and estrone and estradiol.[6][7]
17β-Hydroxysteroid dehydrogenase | |||||||||
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Identifiers | |||||||||
EC no. | 1.1.1.51 | ||||||||
CAS no. | 9015-81-0 | ||||||||
Databases | |||||||||
IntEnz | IntEnz view | ||||||||
BRENDA | BRENDA entry | ||||||||
ExPASy | NiceZyme view | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
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The major reactions catalyzed by 17β-HSD (e.g., the conversion of androstenedione to testosterone) are in fact hydrogenation (reduction) rather than dehydrogenation (oxidation) reactions.
17β-HSDs have been known to catalyze the following redox reactions of sex steroids:
Genes coding for 17β-HSD include:
At least 7 of the 14 isoforms of 17β-HSD are involved in interconversion of 17-ketosteroids and 17β-hydroxysteroids.[12]
# | Gene name | Synonyms | Family | Size (AA ) | Gene location | Cellular location | Substrate specificities | Preferred cofactor | Catalytic preference | Tissue distribution | Expression profile | Pathology |
---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | HSD17B1 | SDR | 328 | 17q21.2 | Cytosol | Estrogens | NADH, NADPH | Reduction | Ovary, endometrium, breast, brain, prostate, placenta | Strongly restricted | Breast cancer, prostate cancer, endometriosis | |
2 | HSD17B2 | SDR | 387 | 16q23.3 | ER | Estrogens, androgens, progestogens | NAD+ | Oxidation | Liver, intestine, endometrium, placenta, pancreas, prostate, colon, bone | Selectively distributed | Breast cancer, prostate cancer, endometriosis, osteoporosis[34] | |
3 | HSD17B3 | SDR | 310 | 9q22.32 | ER | Androgens | NADPH | Reduction | Testis, ovary, blood, saliva, skin, adipose tissue, brain, bone | Strongly restricted | 17β-HSD3 deficiency, prostate cancer[35] | |
4 | HSD17B4 | DBP, MFP2 | SDR | 736 | 5q23.1 | PXS | Fatty acids, bile acids, estrogens, androgens | NAD+ | Oxidation | Liver, heart, prostate, testis, lung, skeletal muscle, kidney, pancreas, thymus, ovary, intestine, placenta, brain, spleen, colon, lymphocytes | Ubiquitous | DBP deficiency, Perrault syndrome, prostate cancer |
5 | AKR1C3 | HSD17B5, 3α-HSD2, PGFS | AKR | 323 | 10p15.1 | Nucleus, cytosol | Androgens, progestogens, estrogens, prostaglandins | NADPH | Reduction | Prostate, mammary gland, liver, kidney, lung, heart, small intestine, colon, uterus, testis, brain, skeletal muscle, adipose tissue | Nearly ubiquitous | Breast cancer, prostate cancer |
6 | HSD17B6 | SDR | 317 | 12q13.3 | Endosomes | Retinoids, androgens, estrogens | NAD+ | Oxidation | Liver, testis, lung, spleen, brain, ovary, kidney, adrenal, prostate | Selectively distributed | ? | |
7 | HSD17B7 | SDR | 341 | 1q23.3 | PM , ER | Cholesterol, estrogens, androgens, progestogens | NADPH | Reduction | Ovary, corpus luteum, uterus, placenta, liver, breast, testis, brain, adrenal gland, small intestine, lung, thymus, prostate, adipose tissue, others | Widely distributed | Breast cancer | |
8 | HSD17B8 | SDR | 261 | 6p21.32 | MC | Fatty acids, estrogens, androgens | NAD+ | Oxidation | Prostate, placenta, kidney, brain, cerebellum, heart, lung, small intestine, ovary, testis, adrenal, stomach | Widely distributed | Polycystic kidney disease | |
9 | RDH5 | HSD17B9 | 318 | 12q13.2 | ER | Retinoids | NADH/NAD+ | Reduction / oxidation | Retina, liver, adipose tissue, blood, others | ? | Fundus albipunctatus | |
10 | HSD17B10 | MHBD | SDR | 261 | Xp11.2 | MC | Fatty acids, bile acids, estrogens, androgens, progestogens, corticosteroids | NAD+ | Oxidation | Liver, small intestine, colon, kidney, heart, brain, placenta, lung, ovary, testis, spleen, thymus, prostate, peripheral blood leukocytes | Nearly ubiquitous | 17β-HSD10 deficiency, MRXS10 , Alzheimer's disease |
11 | HSD17B11 | SDR | 300 | 4q22.1 | ER, EP | Estrogens, androgens | NAD+ | Oxidation | Liver, pancreas, intestine, kidney, adrenal gland, heart, lung, testis, ovary, placenta, sebaceous gland | Nearly ubiquitous | ? | |
12 | HSD17B12 | SDR | 312 | 11p11.2 | ER | Fatty acids, estrogens, androgens | NADPH | Reduction | Heart, skeletal muscle, liver, kidney, adrenal gland, testis, placenta, cerebellum, pancreas, stomach, small intestine, large intestine, trachea, lung, thyroid, esophagus, prostate, aorta, urinary bladder, spleen, skin, brain, ovary, breast, uterus, vagina | Ubiquitous | ? | |
13 | HSD17B13 | SDR | 300 | 4q22.1 | ER, EP | ? | NAD+? | Oxidation? | Liver, bone marrow, lung, ovary, testis, kidney, skeletal muscle, brain, bladder, nasal epithelia | Strongly restricted | ? | |
14 | HSD17B14 | SDR | 270 | 19q13.33 | Cytosol | Estrogens, androgens, fatty acids | NAD+ | Oxidation | Liver, kidney, brain, gallbladder, breast, adrenal, placenta | Widely distributed | Breast cancer (prognostic) | |
15 | RDH11[36][37][38] | PSDR1, HSD17B15 | SDR | 318 | 14q23-24.3 | ER | Retinoids, androgens | NADPH | Reduction | Retina, prostate, brain, testis | ? | Retinitis pigmentosa[39] |
Mutations in HSD17B3 are responsible for 17β-HSD type III deficiency.
Inhibitors of 17β-HSD type II are of interest for the potential treatment of osteoporosis.[34][40]
Some inhibitors of 17β-HSD type I have been identified, for example esters of cinnamic acid and various flavones (e.g. fisetin).[41]
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