Estradiol-17 β -dehydrogenase

Estradiol-17 β -dehydrogenase
	Model of the 17β-HSD type 1 with androstenedione and NADP
	Existing structural data : 1A27 , 1BHS , 1DHT , 1EQU , 1FDS , 1FDT , 1FDU , 1FDV , 1FDW , 1I5R , 1IOL , 1JTV , 1QYV , 1QYW , 1QYX , 3DEY , 3DHE , 3HB4 , 3HB5 , 3KLP , 3KLM , 3KLM
Properties of human protein
Mass / length primary structure	328 amino acids
Cofactor	NADPH
Identifier
Gene names	HSD17B1 EDH17B2; EDHB17; HSD17; SDR28C1
External IDs	OMIM : 109684 ; UniProt : P14061 ; MGI : 105077 ;
Enzyme classification
EC, category	1.1.1.62 , oxidoreductase
Response type	Hydrogenation
Substrate	Estrone + NADPH / H +
Products	Estradiol + NADP +
Occurrence
Parent taxon	Animals (vertebrates), protein of unknown function in fungi and bacteria
	Orthologue

The estradiol-17 β -dehydrogenase (17 β -HSD-1) is the enzyme that the last step in the biosynthesis of estradiol catalyzes the hydrogenation of estrone . The reaction takes place in vertebrates in the cytosol; homologous proteins without a known function are also found in bacteria and fungi.

The dimer, as shown in the picture, is the active form of the enzyme. Monomers cannot catalyze the reaction.

The 17 β -HSD type 1 is in the follicular granulosa cells of gonads , in the mammary gland and in the placenta expressed. Their absence in the adrenal gland promotes androgen formation there. After ovulation , the follicle transforms into a corpus luteum , which continues to produce estradiol. For these estradiol formation no longer the cytosolic 17 β -HSD type 1, but the microsomal 17 β -HSD type 7 responsible.

The availability of estradiol in breast tumors obtained by conversion of estrone by the 17 β arises -HSD type 1 is an important tumor growth factor. Therefore, inhibitors of the enzyme are being investigated as tumor inhibitors.

Basically, all hydroxysteroid dehydrogenases could also catalyze the reverse reaction, but for the oxidation of estradiol other subtypes of 17 are β -HSD responsible.

Catalyzed reaction

+ NADP H / H ⁺ → + NADP ⁺

Estrone is reduced to estradiol.

Individual evidence

↑ Shi R, Lin SX: Cofactor hydrogen bonding onto the protein main chain is conserved in the short chain dehydrogenase / reductase family and contributes to nicotinamide orientation . In: J Biol Chem . 279, No. 16, August, pp. 16778-16785. doi : 10.1074 / jbc.M313156200 . PMID 14966133 .
↑ Payne AG, Hales DB: Overview of Steroidogenic Enzymes in the Pathway from Cholesterol to Active Steroid Hormones . In: Endocrine Reviews . 25, No. 6, 2004, pp. 947-970. doi : 10.1210 / er.2003-0030 . PMID 15583024 .
↑ Purohit A, Tutill HJ, Day JM, Chander SK, Lawrence HR, Allan GM, Fischer DS, Vicker N, Newman SP, Potter BV, Reed MJ: The regulation and inhibition of 17beta-hydroxysteroid dehydrogenase in breast cancer . In: Mol Cell Endocrinol . 248, No. 1-2, August, pp. 199-203. doi : 10.1016 / j.mce.2005.12.003 . PMID 16414180 .

Web links

Wikibooks: Biochemistry and Pathobiochemistry: Steroid Hormone Metabolism - Learning and Teaching Materials

[1] Shi R, Lin SX: Cofactor hydrogen bonding onto the protein main chain is conserved in the short chain dehydrogenase / reductase family and contributes to nicotinamide orientation . In: J Biol Chem . 279, No. 16, August, pp. 16778-16785. doi : 10.1074 / jbc.M313156200 . PMID 14966133 .

[2] Payne AG, Hales DB: Overview of Steroidogenic Enzymes in the Pathway from Cholesterol to Active Steroid Hormones . In: Endocrine Reviews . 25, No. 6, 2004, pp. 947-970. doi : 10.1210 / er.2003-0030 . PMID 15583024 .

[3] Purohit A, Tutill HJ, Day JM, Chander SK, Lawrence HR, Allan GM, Fischer DS, Vicker N, Newman SP, Potter BV, Reed MJ: The regulation and inhibition of 17beta-hydroxysteroid dehydrogenase in breast cancer . In: Mol Cell Endocrinol . 248, No. 1-2, August, pp. 199-203. doi : 10.1016 / j.mce.2005.12.003 . PMID 16414180 .