The 21-dehydroxylation of corticosteroids: evidence for an enol intermediate and the hydroxylation of steroids by fungal cyto-chrome P450: evidence for a stepwise mechanism
dc.contributor.author | Riemland, Elly. | en_US |
dc.date.accessioned | 2009-07-09T18:49:01Z | |
dc.date.available | 2009-07-09T18:49:01Z | |
dc.date.issued | 1984-07-09T18:49:01Z | |
dc.identifier.uri | http://hdl.handle.net/10464/2093 | |
dc.description.abstract | Two enzyme mechanisms were examined: the 21-dehydroxylation of corticosteroids by the anaerobe Eubacterium l en tum, and the hydroxylation of steroids by fungal cytochrome P450. Deuterium labelling techniques were used to study the enzymic dehydroxylation. Corticosteroids doubly labelled (2H) at the C-21 position were incubated with a culture of Eubacterium lentum. It was found that t he enzymic dehydroxylation proceeded with the loss of one 2H f rom C-21 per molecule of substrate. The kinetic isotope ef fect f or the reaction was found to be k~kD = 2. 28. These results suggest that enzyme/substr ate binding in this case may proceed via t he enol form of the substrate. Also , it appears that this binding is, at least in part, the rate determining step of t he reaction. The hydroxylation of steroids by fungal cytochrome P450 was examined by means of a product study. Steroids with a double bond at the A8 (9), ~( lO ), or ~ (ll) position were synthesized. These steroids were then incubated with fungal strains known to use a cytochrome P450 monooxygenase to hydroxylate at positions allylic to these doubl e bonds. The products formed in these incubations indicated that the double bonds had migrated during allylic hydroxylat ion. This suggests that a carbon centred radical or ion may be an intermediate i n the cytochrome P450 cat alytic cycle. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Brock University | en_US |
dc.subject | Corticosterone. | en_US |
dc.subject | Steroids. | en_US |
dc.subject | Hydroxylation. | en_US |
dc.subject | Cytochrome P-450. | en_US |
dc.subject | Fungi--Cytology. | en_US |
dc.title | The 21-dehydroxylation of corticosteroids: evidence for an enol intermediate and the hydroxylation of steroids by fungal cyto-chrome P450: evidence for a stepwise mechanism | 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 | 2021-08-02T01:32:43Z |