Genomes and Genes
3 alpha hydroxysteroid dehydrogenase
Gene Symbol: 3 alpha hydroxysteroid dehydrogenase
Description: aldo-keto reductase family 1, member C14
Alias: Akr1c9, 3-alpha-hydroxysteroid dehydrogenase, 3-alpha-HSD, hydroxyprostaglandin dehydrogenase, steroid 3-alpha-dehydrogenase
Products: 3 alpha hydroxysteroid dehydrogenase
- Pawlowski J, Huizinga M, Penning T. Isolation and partial characterization of a full-length cDNA clone for 3 alpha-hydroxysteroid dehydrogenase: a potential target enzyme for nonsteroidal anti-inflammatory drugs. Agents Actions. 1991;34:289-93 pubmed..cytosol is a monomeric (Mr 34000) NAD(P)+ dependent oxidoreductase which displays 9-, 11- & 15-hydroxyprostaglandin dehydrogenase activity...
- Usui E, Okuda K, Kato Y, Noshiro M. Rat hepatic 3 alpha-hydroxysteroid dehydrogenase: expression of cDNA and physiological function in bile acid biosynthetic pathway. J Biochem. 1994;115:230-7 pubmed..abstract truncated at 250 words) ..
- Khanna M, Qin K, Cheng K. Distribution of 3 alpha-hydroxysteroid dehydrogenase in rat brain and molecular cloning of multiple cDNAs encoding structurally related proteins in humans. J Steroid Biochem Mol Biol. 1995;53:41-6 pubmed..We are currently investigating the functional relationship between the enzymes encoded by these human cDNAs and 3 alpha-hydroxysteroid dehydrogenase. ..
- Heredia V, Cooper W, Kruger R, Jin Y, Penning T. Alanine scanning mutagenesis of the testosterone binding site of rat 3 alpha-hydroxysteroid dehydrogenase demonstrates contact residues influence the rate-determining step. Biochemistry. 2004;43:5832-41 pubmed..and steroid turnover by these enzymes were analyzed using rat 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD, AKR1C9) as the protein model...
- Hoog S, Pawlowski J, Alzari P, Penning T, Lewis M. Three-dimensional structure of rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase: a member of the aldo-keto reductase superfamily. Proc Natl Acad Sci U S A. 1994;91:2517-21 pubmed..In the 3 alpha-HSD structure these residues are on the periphery of the barrel and are unlikely to participate in catalysis. ..
- Bennett M, Schlegel B, Jez J, Penning T, Lewis M. Structure of 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase complexed with NADP+. Biochemistry. 1996;35:10702-11 pubmed..Knowledge of the position of this water molecule, combined with the stereochemistry of hydride transfer, suggests that the alpha face of a bound steroid will be oriented toward the side of the apolar cleft containing Trp 86. ..
- Cooper W, Jin Y, Penning T. Elucidation of a complete kinetic mechanism for a mammalian hydroxysteroid dehydrogenase (HSD) and identification of all enzyme forms on the reaction coordinate: the example of rat liver 3alpha-HSD (AKR1C9). J Biol Chem. 2007;282:33484-93 pubmed..the complete kinetic mechanism of a mammalian HSD using rat 3alpha-HSD of the aldo-keto reductase superfamily (AKR1C9) with the substrate pairs androstane-3,17-dione and NADPH (reduction) and androsterone and NADP(+) (oxidation)...
- Patte Mensah C, Penning T, Mensah Nyagan A. Anatomical and cellular localization of neuroactive 5 alpha/3 alpha-reduced steroid-synthesizing enzymes in the spinal cord. J Comp Neurol. 2004;477:286-99 pubmed..These results are the first demonstrating that oligodendrocytes and neurons of the SC possess the key enzymatic complex for synthesizing potent neuroactive steroids that may control spinal sensorimotor processes. ..
- Stolz A, Rahimi Kiani M, Ameis D, Chan E, Ronk M, Shively J. Molecular structure of rat hepatic 3 alpha-hydroxysteroid dehydrogenase. A member of the oxidoreductase gene family. J Biol Chem. 1991;266:15253-7 pubmed..The significant homology of 3 alpha-HSD with both prostaglandin F synthetase and aldose reductases suggest a subdivision of monomeric, NADPH reductases within the larger oxidoreductases superfamily. ..
- Del Bello B, Maellaro E, Sugherini L, Santucci A, Comporti M, Casini A. Purification of NADPH-dependent dehydroascorbate reductase from rat liver and its identification with 3 alpha-hydroxysteroid dehydrogenase. Biochem J. 1994;304 ( Pt 2):385-90 pubmed..Internal primary structure data were obtained from CNBr-derived fragments and definitely proved the identity of NADPH-dependent DHAA reductase with 3 alpha-hydroxysteroid dehydrogenase. ..
- Penning T, Abrams W, Pawlowski J. Affinity labeling of 3 alpha-hydroxysteroid dehydrogenase with 3 alpha-bromoacetoxyandrosterone and 11 alpha-bromoacetoxyprogesterone. Isolation and sequence of active site peptides containing reactive cysteines; sequence confirmation using nucleotid. J Biol Chem. 1991;266:8826-34 pubmed..By contrast the 11 alpha-bromoacetoxy group in Br11P labeled several reactive cysteines which may be involved in the binding of glucocorticoids and NSAIDs. ..
- Pawlowski J, Huizinga M, Penning T. Cloning and sequencing of the cDNA for rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase. J Biol Chem. 1991;266:8820-5 pubmed..It is identical to dihydrodiol dehydrogenase and it can function as a 9-, 11-, and 15-hydroxyprostaglandin dehydrogenase. Its reactions are potently inhibited by the nonsteroidal anti-inflammatory drugs (NSAIDs)...
- Guo J, Li L, Zhou S, Su Y, Li X, Sun J, et al. Butylated hydroxyanisole alters rat 5?-reductase and 3?-hydroxysteroid dehydrogenase: Implications for influences of neurosteroidogenesis. Neurosci Lett. 2017;653:132-138 pubmed publisher..In conclusion, butylated hydroxyanisole is a potent inhibitor of SRD5A1 and AKR1C14, thus reducing the formation of active neurosteroids. ..
- Lin H, Hung C, Moore M, Penning T. Genomic structure of rat 3alpha-hydroxysteroid/dihydrodiol dehydrogenase (3alpha-HSD/DD, AKR1C9). J Steroid Biochem Mol Biol. 1999;71:29-39 pubmed..It is unknown whether the type 2 and type 3 3alpha-HSD/DD genes represent pseudo-genes or whether they represent genes that are differentially expressed in other rat tissues. ..
- Heredia V, Penning T. Dissection of the physiological interconversion of 5alpha-DHT and 3alpha-diol by rat 3alpha-HSD via transient kinetics shows that the chemical step is rate-determining: effect of mutating cofactor and substrate-binding pocket residues on catalysis. Biochemistry. 2004;43:12028-37 pubmed..To identify the rate-determining step in this physiologically important reaction, rat liver 3alpha-HSD (AKR1C9) was used as the protein model for the human homologues in fluorescence stopped-flow transient kinetic and kinetic ..
- Cheng K, White P, Qin K. Molecular cloning and expression of rat liver 3 alpha-hydroxysteroid dehydrogenase. Mol Endocrinol. 1991;5:823-8 pubmedComplementary DNA clones encoding 3 alpha-hydroxysteroid dehydrogenase (3 alpha HSD) were isolated from a rat liver cDNA lambda gt11 expression library using monoclonal antibodies as probes. The sizes of the cDNA inserts ranged from 1...
- Kimoto T, Ishii H, Higo S, Hojo Y, Kawato S. Semicomprehensive analysis of the postnatal age-related changes in the mRNA expression of sex steroidogenic enzymes and sex steroid receptors in the male rat hippocampus. Endocrinology. 2010;151:5795-806 pubmed publisher..These results suggest that the hippocampal sex steroidogenic properties are substantially altered during the postnatal development processes, which might contribute to brain sexual maturation. ..