Multiple functions of type 10 17beta-hydroxysteroid dehydrogenase.
Human 17beta-hydroxysteroid dehydrogenase type 10 (17beta-HSD10) is a mitochondrial enzyme encoded by the SCHAD gene, which escapes chromosome X inactivation. 17Beta-HSD10/SCHAD mutations cause a spectrum of clinical conditions, from mild mental retardation to progressive infantile neurodegeneration. 17Beta-HSD10/SCHAD is essential for the metabolism of isoleucine and branched-chain fatty acids. It can inactivate 17beta-estradiol and steroid modulators of GABA(A) receptors, and convert 5alpha-androstanediol into 5alpha-dihydrotestosterone (DHT). Certain malignant prostatic epithelial cells contain high levels of 17beta-HSD10, generating 5alpha-DHT in the absence of testosterone. 17Beta-HSD10 has an affinity for amyloid-beta peptide, and might be linked to the mitochondrial dysfunction seen in Alzheimer's disease. This versatile enzyme might provide a new drug target for neuronal excitability control and for intervention in Alzheimer's disease and certain cancers.
Yang
Song-Yu
SY
Department of Pharmacology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA. yang.songyu@yahoo.com
He
Xue-Ying
XY
Schulz
Horst
H
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000544:Alzheimer Disease / Q000201:enzymology / Q000209:etiology; D000818:Animals; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D007532:Isoleucine / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D013256:Steroids / Q000378:metabolism
D012739:Gonadal Steroid Hormones; D018377:Neurotransmitter Agents; D013256:Steroids; D007532:Isoleucine; D015067:17-Hydroxysteroid Dehydrogenases; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human