The investigation of the reduction mechanism of the 5a-reductase enzyme of Penicillium decumbens /
dc.contributor.author | Hsü, Wei-li. | en_US |
dc.date.accessioned | 2009-05-21T13:25:22Z | |
dc.date.available | 2009-05-21T13:25:22Z | |
dc.date.issued | 1990-05-21T13:25:22Z | |
dc.identifier.uri | http://hdl.handle.net/10464/1291 | |
dc.description.abstract | The 5a-reductase of Penicillium decumbens ATCC 10436 was used as a model for the mammalian enzyme to investigate the mechanism of reduction of testosterone to 5adihydrotestosterone . The purpose of this study was to search for specific 5a-reductase inhibitors which antagonize prostate cancer . In a whole-cell biotransformation mode, this organism reduced testosterone (1) to 5a-dihydrosteroids (8) and 5aandrostane- 3, 17-dione (9) in yields of 28% and 37% respectively. Control experiments have shown that 5aandrostane- 3, 17-dione (9) can be produced from the corresponding alcohol (8) in a subsequent reaction separate from that catalysed by the 5a-reductase enzyme . Androst-4- ene-3, 17-dione (2) is reduced to give only (9) with a recovery of 80% The stereochemistry of the reduction was determined by 500 MHz ^H NMR analysis of the products resulting from the deuterium labelled substrates. The results were obtained by an analysis of the NOE difference spectra, double-quantum filtered phase sensitive COSY 2-D spectra, and ^^c-Ir 2-D shift correlation spectra of deuterium labelled products. According to the unambiguous assignment of the signals due to H-4a and H-4Ii in 5a-dihydro steroids, the NMR data show clearly that addition of hydrogen to the 4{5)K bond has occurred in a trans manner at positions 413 and 5a. To Study the reduction mechanism of this enzyme, several substrates were prepared as following; 3-methyleneandrost-4-en- 17fi-ol(3), androst-4-en-17i5-ol(5) , androst-4-en-3ii, 17fi-diol (6) and 4, 5ii-epoxyandrostane-3, 17-dione (7) . Results suggest that this enzyme system requires an oxygen atom at the 3-position of the steroid in order to bind the substrate. Furthermore, the mechanism of this 5a-reductase may proceed via direct addition of hydrogen at the 4,5 position without involvement of a carbonyl group as an intermediate. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Brock University | en_US |
dc.subject | Penicillium decumbens. | en_US |
dc.subject | Enzyme inhibitors. | en_US |
dc.subject | Enzymes | en_US |
dc.subject | Reduction (Chemistry) | en_US |
dc.title | The investigation of the reduction mechanism of the 5a-reductase enzyme of Penicillium decumbens / | en_US |
dc.type | Electronic Thesis or Dissertation | en |
dc.degree.name | M.Sc. Chemistry | en_US |
dc.degree.level | Masters | en_US |
dc.contributor.department | Department of Chemistry | en_US |
dc.degree.discipline | Faculty of Mathematics and Science | en_US |
refterms.dateFOA | 2021-08-07T02:15:43Z |