Roles of type 10 17beta-hydroxysteroid dehydrogenase in intracrinology and metabolism of isoleucine and fatty acids.
Human type 10 17beta-hydroxysteroid dehydrogenase (HSD) is a homotetrameric protein located in mitochondria. This enzyme was alternatively named short chain L-3-hydroxyacyl-CoA dehydrogenase (SCHSD). This NAD(H)-dependent dehydrogenase is essential for the metabolism of branched-chain fatty acids and isoleucine, and is expressed in a variety of tissues, e.g., prostate, brain, liver, and heart. This enzyme inactivates 17beta-estradiol and exhibits a strong oxidative 3alpha-HSD activity to convert 5alpha-androstanediol and allopregnanolone into 5alpha-dihydrotestosterone (5alpha-DHT) and 5alpha-dihydroprogesterone, respectively, in living cells. Certain malignant prostatic epithelial cells and activated astrocytes in Alzheimer's disease patient's brain contain extraordinarily high levels of this enzyme. This mitochondrial dehydrogenase enables prostate cancer cells to generate 5alpha-DHT in the absence of testosterone. Its inactivation of allopregnanolone is important to the modulation of GABA(A) receptor. Among steroidogenic enzymes 17beta-HSD10 plays a significant part in the intracrinology. Although this protein has an affinity for amyloid-beta peptide, its role in the pathogenesis of Alzheimer's disease is far from clear. Additional knowledge of this versatile enzyme would provide the foundation for designing new drugs aimed at treating some neurological diseases and certain types of cancers.
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Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA.
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D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000502:physiology; D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000037:antagonists & inhibitors / Q000502:physiology; D000592:Amino Acid Metabolism, Inborn Errors / Q000378:metabolism; D000728:Androgens / Q000096:biosynthesis; D000818:Animals; D004967:Estrogens / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D007532:Isoleucine / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology; D008969:Molecular Sequence Data; D018377:Neurotransmitter Agents / Q000378:metabolism
D000728:Androgens; D004967:Estrogens; D005227:Fatty Acids; D018377:Neurotransmitter Agents; D007532:Isoleucine; D015067:17-Hydroxysteroid Dehydrogenases; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human