Masters Degrees (Biochemistry)

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Browsing Masters Degrees (Biochemistry) by Subject "Adrenal 16 alpha-hydroxyprogesterone -- Metabolism"

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    The metabolism of adrenal 11beta-hydroxyprogesterone, 11keto-progesterone and 16alpha-hydroxyprogesterone by steroidogenic enzymes
    (Stellenbosch : Stellenbosch University, 2017-03) Van Rooyen, Desmare; Swart, Amanda C.; Swart, Pieter; Stellenbosch University. Faculty of Science. Dept. of Biochemistry.
    ENGLISH ABSTRACT: This study describes ■ Cytochrome P450 11β-hydroxylase (CYP11B1) and cytochrome P450 aldosterone synthase (CYP11B2) both catalyse the 11β-hydroxylation of progesterone (P4) to 11β-hydroxyprogesterone (11OHP4). ■ the 11β-hydroxylation of 16α-hydroxyprogesterone (16OHP4) catalysed by CYP11B2 only yielding 4-pregnen-11β,16α-diol-3,20-dione (11,16diOHP4). ■ Both 5α-reductase isozymes 1 and 2 (SRD5A1 and SRD5A2) catalyse the reduction of 11OHP4, 11keto-progesterone (11KP4), 16OHP4 and 11,16diOHP4 to 5α-pregnan-11β- ol,3,20-dione (11OH-DHP4), 11keto-dihydroprogesterone (11K-DHP4), 5α-pregnan-16α- ol,3,20-dione (16OH-DHP4) and 5α-pregnan-11β,16α-diol-3,20-dione (11,16diOH-DHP4). ■ AKR1C2 catalyses the 3α-reduction of 11OH-DHP4, 11K-DHP4 and 16OH-DHP4 2 to 3α,11β- dihydroxy-5α-pregnan-20-one (3,11diOH-DHP4), 5α-pregnan-3α-ol-11,20-dione (alfaxalone) and to 3α,16α-dihydroxy-5α-pregnan-20-one (3,16diOH-DHP4). ■ Cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1) catalyses the metabolism of alfaxalone to 11keto-androsterone (11KAST) –converting a C21 steroid to a C19 androgenic steroid. ■ 11OHP4 and 11KP4 are metabolised in the LNCaP cell model. 11OHP4 was metabolised to 11KP4, 11K-DHP4, alfaxalone and 11keto-dihydrotestosterone (11KDHT) while 11KP4 was metabolised to 11K-DHP4, alfaxalone and 11KDHT. ■ the activation of the androgen- and progesterone receptors by 11OHP4, 11KP4, 16OHP4 and their 5α-reduced metabolites.