Cytochrome b5 modulation of 17 alpha hydroxylase and 17-20 lyase (CYP17) activities in steroidogenesis

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dc.contributor.author Kaderbhai, Mustak A.
dc.contributor.author Akhtar, Kalim M.
dc.contributor.author Kelly, Steven L.
dc.date.accessioned 2009-09-25T14:17:56Z
dc.date.available 2009-09-25T14:17:56Z
dc.date.issued 2005
dc.identifier.citation Kaderbhai , M A , Akhtar , K M & Kelly , S L 2005 , ' Cytochrome b5 modulation of 17 alpha hydroxylase and 17-20 lyase (CYP17) activities in steroidogenesis ' Journal of Endocrinology , pp. 267-2274 . en
dc.identifier.issn 1479-6805
dc.identifier.other PURE: 119099
dc.identifier.other dspace: 2160/3092
dc.identifier.uri http://hdl.handle.net/2160/3092
dc.description Akhtar, M. K., Kelly, S. L.,, Kaderbhai, M. A. (2005). Cytochrome b5 modulation of 17 alpha hydroxylase and 17-20 lyase (CYP17) activities in steroidogenesis. Journal of Endocrinology, 187, (2), 267-2274 en
dc.description.abstract CYP17 is a steroidogenic enzyme located in the zona fasciculata and zona reticularis of the adrenal cortex and gonad tissues and which has dual functions – hydroxylation and as a lyase. The first activity gives hydroxylation of pregnenolone and progesterone at the C17 position to generate 17-hydroxypregnenolone and 17-hydroxyprogesterone, while the second enzymic activity cleaves the C17–C20 bond of 17-hydroxypregnenolone and 17-hydroxyprogesterone to form dehydroepiandro-sterone and androstenedione respectively. The modulation of these two activities occurs through cytochrome b5. Association of cytochrome b5 and CYP17 is thought to be based primarily on electrostatic interactions in which the negatively charged residues pair up with positively charged residues on the proximal surface of the CYP17 molecule. Non-specific interactions of the hydrophobic membrane regions of cytochrome b5 and CYP17 are also thought to play a crucial role in the association of these two haemoproteins. Although cytochrome b5 is known to stimulate CYP activity by contributing the second electron in the catalytic cycle, in the case of CYP17, the mechanism of cleavage stimulation proceeds via an allosteric mode. It is hypothesised that cytochrome b5 promotes the cleavage by aligning the iron–oxygen complex attack onto the C20 rather than the C17 atom of the steroid substrate molecule. Thus, further understanding of the mechanism of modulation by cytochrome b5 of the hydroxylase and lyase activities should shed new insights on developing therapeutic targets in CYP17-linked biochemical processes such as adrenarche, polycystic ovary syndrome and prostate cancer. en
dc.format.extent 2008 en
dc.language.iso eng
dc.relation.ispartof Journal of Endocrinology en
dc.title Cytochrome b5 modulation of 17 alpha hydroxylase and 17-20 lyase (CYP17) activities in steroidogenesis en
dc.type Text en
dc.type.publicationtype Article (Journal) en
dc.identifier.doi http://dx.doi.org/10.1677/joe.1.06375
dc.contributor.institution Institute of Biological, Environmental and Rural Sciences en
dc.description.status Peer reviewed en


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