Multiple steps determine the overall rate of the reduction of 5α-dihydrotestosterone catalyzed by human type 3 3α-hydroxysteroid dehydrogenase: Implications for the elimination of androgens

Biochemistry

Volumn 45, Issue 43, 2006, Pages 13054-13063

  Jin, Yi ^a   Penning, Trevor M ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CATALYSIS; DEUTERIUM; ISOMERIZATION; MOLECULAR STRUCTURE; REDUCTION; SUBSTITUTION REACTIONS;

ANDROGENS; DIHYDROTESTOSTERONE; TRANSIENT KINETICS;

ENZYME KINETICS;

3ALPHA HYDROXYSTEROID DEHYDROGENASE; ANDROGEN; ANDROSTANOLONE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE;

ARTICLE; CATALYSIS; ENZYME ACTIVITY; ENZYME KINETICS; ESCHERICHIA COLI; GENE OVEREXPRESSION; GENETIC TRANSCRIPTION; LIGAND BINDING; NONHUMAN; PRIORITY JOURNAL; STEADY STATE;

3-ALPHA-HYDROXYSTEROID DEHYDROGENASE (B-SPECIFIC); ANDROGENS; DIHYDROTESTOSTERONE; HUMANS; KINETICS; MOLECULAR STRUCTURE; NADP; OXIDATION-REDUCTION; RECEPTORS, ANDROGEN;

EID: 33751096178     PISSN: 00062960     EISSN: None     Source Type: Journal    
DOI: 10.1021/bi060591r     Document Type: Article

References (42)

1. Penning, T. M., Jin, Y., Steckelbroeck, S., Rizner, T. L., and Lewis, M. (2004) Structure-function of human 3α-hydroxysteroid dehydrogenases: Genes and proteins, Mol. Cell. Endocrinol. 215, 63-72.
2. Jez, J. M., Flynn, T. G., and Penning, T. M. (1997) A new nomenclature for the aldo-keto reductase superfamily, Biochem. Pharmacol. 54, 639-647.
3. Hyndman, D., Bauman, D. R., Heredia, V. V., and Penning, T. M. (2003) The aldo-keto reductase superfamily homepage, Chem.-Biol. Interact. 143-144, 621-631.
4. Penning, T. M. (1997) Molecular endocrinology of hydroxysteroid dehydrogenases, Endocr. Rev. 18, 281-305.
5. Penning, T. M. (2003) Hydroxysteroid dehydrogenases and prereceptor regulation of steroid hormone action, Hum. Reprod. Update 9, 193-205.
6. Bauman, D. R., Steckelbroeck, S., and Penning, T. M. (2004) The roles of aldo-keto reductases in steroid hormone action, Drug News Perspect. 17, 563-578.
7. Penning, T. M., Burczynski, M. E., Jez, J. M., Hung, C.-F., Lin, H.-K., Ma, H., Moore, M., Palackal, N., and Ratnam, K. (2000) Human 3α-hydroxysteroid dehydrogenase isoforms (AKR1CI-AKR1C4) of the aldo-keto reductase superfamily: Functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones, Biochem. J. 351, 67-77.
8. Rizner, T. L., Lin, H. K., Peehl, D. M., Steckelbroeck, S., Bauman, D. R., and Penning, T. M. (2003) Human type 3 3α-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2) and androgen metabolism in prostate cells, Endocrinology 144, 2922-2932.
9. Penning, T. M., Steckelbroeck, S., Bauman, D. R., Miller, M. W., Jin, Y., Peehl, D. M., Fung, K. M., and Lin, H. K. (2006) Aldo keto reductase (AKR) 1C3: Role in prostate disease and the development of specific inhibitors, Mol. Cell. Endocrinol. 316, 1300-1309.
10. Steckelbroeck, S., Jin, Y., Gopishetty, S., Oyesanmi, B., and Penning, T. M. (2003) Human cytosolic 3α-hydroxysteroid dehydrogenases (3α-HSDs) of the aldo-keto reductase (AKR) superfamily display significant 3β-hydroxysteroid dehydrogenase (3β-HSD) activity: Implications for steroid hormone metabolism and activation, J. Biol. Chem. 279, 10784-10795.
11. Davies, P., and Eaton, C. L. (1991) Regulation of prostate growth, J. Endocrinol. 131, 5-17.
12. Wilson, J. D. (1996) Androgens, in Goodman & Gilman's Pharmacological Basis of Therapeutics (Hardman, J. F., and Limbird, L. E., Eds.) pp 1441-1457, McGraw-Hill, New York.
13. + bound to 3α-hydroxysteroid/ dihydrodiol dehydrogenase, Structure 5, 799-812.
14. + and ursodeoxycholate, Biochemistry 40, 10161-10168.
15. + at 1.25-Å resolution, J. Biol. Chem. 276, 42091-42098.
16. Couture, J. F., Legrand, P., Cantin, L., Luu-The, V., Labrie, F., and Breton, R. (2003) Human 20α-hydroxysteroid dehydrogenase: Crystallographic and site-directed mutagenesis studies lead to the identification of an alternative binding site for C21-steroids, J. Mol. Biol. 331, 593-604.
17. Komoto, J., Yamada, T., Watanabe, K., and Takusagawa, F. (2004) Crystal structure of human prostaglandin F synthase (AKR 1C3), Biochemistry 43, 2188-2198.
18. Jez, J. M., Bennett, M. J., Schlegel, B. P., Lewis, M., and Penning, T. M. (1997) Comparative anatomy of the aldo-keto reductase superfamily, Biochem. J. 326, 625-636.
19. Trauger, J. W., Jiang, A., Stearns, B. A., and LoGrasso, P. V. (2002) Kinetics of allopregnanolone formation catalyzed by human 3α- hydroxysteroid dehydrogenase type III (AKR1C2), Biochemistry 41, 13451-13459.
20. Askonas, L. J., Ricigliano, J. W., and Penning, T. M. (1991) The kinetic mechanism catalysed by homogeneous rat liver 3α-hydroxysteroid dehydrogenase: Evidence for binary and ternary dead-end complexes containing non-steroidal anti-inflammatory drugs, Biochem. J. 278, 835-841.
21. +/NADPH and alrestatin-like inhibitors, Biochemistry 33, 7157-7165.
22. Neuhauser, W., Haltrich, D., Kulbe, K. D., and Nidetzky, B. (1997) NAD(P)H-dependent aldose reductase from the xylose-assimilating yeast Candida tenuis: Isolation, characterization and biochemical properties of the enzyme, Biochem. J. 326, 683-692.
23. Grimshaw, C. E., Bohren, K. M., Lai, C.-J., and Gabbay, K. H. (1995) Human aldose reductase: Rate constants for a mechanism including interconversion of ternary complexes by recombinant wild-type enzyme, Biochemistry 34, 14323-14330.
24. Nidetzky, B., Klimacek, M., and Mayr, P. (2001) Transient-state and steady-state kinetic studies of the mechanism of NADH-dependent aldehyde reduction catalyzed by xylose reductase from the yeast Candida tenuis, Biochemistry 40, 10371-10381.
25. Heredia, V. V., and Penning, T. M. (2004) Dissection of the physiological interconversion of 5α-DHT and 3α-diol by rat 3α-HSD via transient kinetics shows that the chemical step is rate-determining: Effect of mutating cofactor and substrate-binding pocket residues on catalysis, Biochemistry 43, 12028-12037.
26. Penning, T. M., Jin, Y., Heredia, V. V., and Lewis, M. (2003) Structure-function relationships in 3α-hydroxysteroid dehydrogenases: A comparison of the rat and human isoforms, J. Steroid Biochem. Mol. Biol. 85, 247-255.
27. Jin, Y., Cooper, W. C., and Penning, T. M. (2003) Examination of the differences in structure-function of human and rat 3α-hydroxysteroid dehydrogenase, Chem.-Biol. Interact. 143, 383-392.
28. Ratnani, K., Ma, H., and Penning, T. M. (1999) The arginine 276 anchor for NADP(H) dictates fluorescence kinetic transients in 3α-hydroxysteroid dehydrogenase, a representative aldo-keto reductase, Biochemistry 38, 7856-7864.
29. Burczynski, M. E., Harvey, R. G., and Penning, T. M. (1998) Expression and characterization of four recombinant human dihydrodiol dehydrogenase isoforms: Oxidation of trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene to the activated o-quinone metabolite benzo[a]pyrene-7,8-dione, Biochemistry 37, 6781-6790.
30. Bradford, M. M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding, Anal. Biochem. 72, 248-254.
31. Northrop, D. B. (1982) Deuterium and tritium kinetic isotope effects on initial rates, Methods Enzymol. 87, 607-625.
32. Johnson, K. A. (1992) Transient-state kinetic analysis of enzyme reaction pathways, Methods Enzymol. 134, 677-705.
33. Kuzmic, P. (1996) Program DynaFit for the Analysis of Enzyme Kinetic Data: Application to HIV Proteinase, Anal. Biochem. 237, 260-273.
34. Jez, J. M., Schlegel, B. P., and Penning, T. M. (1996) Characterization of the substrate binding site in rat liver 3α-hydroxysteroid/dihydrodiol dehydrogenase: The roles of tryptophans in ligand binding and protein fluorescence, J. Biol. Chem. 271, 30190-20198.
35. Makridakis, N., Akalu, A., and Reichardt, J. K. V. (2004) Identification and characterization of somatic steroid 5α-reductase (SRD5A2) mutations in human prostate cancer tissues, Oncogene 23, 7399-7405.
36. Segal, I. H. (1975) Enzyme Kinetics, pp 560-564. John Wiley and Sons, New York.
37. Heredia, V. V., Cooper, W. C., Kruger, R. G., Jin, Y., and Penning, T. M. (2004) Alanine scanning mutagenesis of the testosterone binding site of rat 3α-hydroxysteroid dehydrogenase demonstrates contact residues influence the rate-determining step, Biochemistry 43, 5832-5841.
38. Wilson, D. K., Nakano, T., Petrash, J. M., Gabbay, K. H., and Quiocho, F. A. (1992) An unlikely sugar substrate site in the 1.65 Å structure of the human aldose reductase holoenzyme implicated in diabetic complications, Science 257, 81-84.
39. + and the basis for single and dual co-substrate specificity in family 2 aldo-keto reductases, Biochem. J. 373, 319-326.
40. Hoog, S. S., Pawlowski, J. E., Alzari, P. M., Penning, T. M., and Lewis, M. (1994) Three-dimensional structure of rat liver 3α-hydroxysteroid/ dihydrodiol dehydrogenase: A member of the aldo-keto reductase superfamily, Proc. Natl. Acad. Sci. U.S.A. 91, 2517-2521.
41. +, Biochemistry 35, 10702-10711.
42. Jin, Y., and Penning, T. M. (2006) Molecular docking simulations of steroid substrates into human cytosolic hydroxysteroid dehydrogenases (AKR1C1 and AKR1C2): Insights into positional and stereochemical preferences, Steroids 71, 380-391.