3beta-Hydroxysteroid dehydrogenase

From Infogalactic: the planetary knowledge core
Jump to: navigation, search
3β-hydroxysteroid dehydrogenase/Δ-5-4 isomerase
Identifiers
EC number 1.1.1.145
CAS number Template:CAS
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 / EGO
hydroxy-Δ-5-steroid dehydrogenase,
3β- and steroid Δ-isomerase 1
Identifiers
Symbol HSD3B1
Alt. symbols HSDB3, HSD3B
Entrez 3283
HUGO 5217
OMIM 109715
RefSeq NM_000862
UniProt P14060
Other data
EC number 1.1.1.145
Locus Chr. 1 p13-p11
hydroxy-Δ-5-steroid dehydrogenase,
3β- and steroid Δ-isomerase 2
Identifiers
Symbol HSD3B2
Entrez 3284
HUGO 5218
OMIM 613890
RefSeq NM_000198
UniProt P26439
Other data
EC number 1.1.1.145
Locus Chr. 1 p13.1

3β-Hydroxysteroid dehydrogenase/Δ5-4 isomerase (3β-HSD) (EC 1.1.1.145) is an enzyme that catalyzes the biosynthesis of progesterone from pregnenolone, 17α-hydroxyprogesterone from 17α-hydroxypregnenolone, and androstenedione from dehydroepiandrosterone (DHEA) in the adrenal gland. It is the only enzyme in the adrenal pathway of corticosteroid synthesis that is not a member of the cytochrome P450 family.[1] In humans, there are two 3β-HSD isozymes encoded by the HSD3B1 and HSD3B2 genes.

3β-HSD is also known as delta Δ5-4-isomerase, which catalyzes the oxidative conversion of Δ5-3-β-hydroxysteroids to the Δ4-3-keto configuration and is, therefore, essential for the biosynthesis of all classes of hormonal steroids, namely progesterone, glucocorticoids, mineralocorticoids, androgens, and estrogens.[2]

The 3β-HSD complex is responsible for the conversion of:

Reaction

3β-HSD belongs to the family of oxidoreductases, to be specific, those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. This enzyme participates in C21-steroid hormone metabolism and androgen and estrogen metabolism.

3β-HSD catalysis|catalyzes the chemical reaction:

a 3β-hydroxy-Δ5-steroid + NAD+ \rightleftharpoons a 3-oxo-Δ5-steroid + NADH + H+

Thus, the two substrates of this enzyme are 3β-hydroxy-Δ5-steroid and NAD+, whereas its three products are 3-oxo-Δ5-steroid, NADH, and H+.

Isozymes

Humans express two 3β-HSD isozymes, HSD3B1 (type I) and HSD3B2 (type II).[3] The type I isoenzyme is expressed in placenta and peripheral tissues, whereas the type II 3β-HSD isoenzyme is expressed in the adrenal gland, ovary, and testis.

Nomenclature

The systematic name of this enzyme class is 3β-hydroxy-Δ5-steroid:NAD+ 3-oxidoreductase. Other names in common use include:

  • progesterone reductase
  • Δ5-3β-hydroxysteroid dehydrogenase
  • 3β-hydroxy-5-ene steroid dehydrogenase
  • 3β-hydroxy steroid dehydrogenase/isomerase
  • 3β-hydroxy-Δ5-C27-steroid dehydrogenase/isomerase
  • 3β-hydroxy-Δ5-C27-steroid oxidoreductase
  • 3β-hydroxy-5-ene-steroid oxidoreductase
  • steroid-Δ5-3β-ol dehydrogenase
  • 3β-HSDH
  • 5-ene-3β-hydroxysteroid dehydrogenase
  • 3β-hydroxy-5-ene-steroid dehydrogenase

Inhibitors

3β-HSD is inhibited by trilostane.[4]

Biosynthetic pathway

Human steroidogenesis, showing reactions of 3β-HSD near-left in green box. 
Corticosteroid biosynthetic pathway in the rat, showing reaction catalyzed by 3β-HSD (second arrow from the top). 

Clinical significance

A deficiency in the type II form through mutations in HSD3B2 is responsible for a rare form of congenital adrenal hyperplasia.[5] No human condition has yet been linked to a deficiency in the type I enzyme. Its importance in placental progesterone production expression suggests that such a mutation would be embryonically lethal.

The fetal adrenal cortex lacks expression of the enzyme early on, thus mineralocorticoids (i.e. aldosterone) and glucocorticoids (i.e. cortisol) cannot be synthesized. This is significant because cortisol induces type II pneumocytes of the lungs to synthesize and secrete pulmonary surfactant; without pulmonary surfactant to reduce the alveolar surface tension, premature neonates may die of neonatal respiratory distress syndrome. If delivery is unavoidable (i.e. because of placental abruption, or pre-eclampsia/HELLP syndrome), then glucocorticoids (i.e. cortisol) can be administered to induce type II pneumocytes to synthesize and secrete pulmonary surfactant, improving the chances of newborn survival (by preventing neonatal respiratory distress syndrome).

See also

References

  1. Lua error in package.lua at line 80: module 'strict' not found.
  2. Lua error in package.lua at line 80: module 'strict' not found.
  3. Lua error in package.lua at line 80: module 'strict' not found.
  4. Lua error in package.lua at line 80: module 'strict' not found.
  5. Lua error in package.lua at line 80: module 'strict' not found.

Further reading

  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.