LlaHydroxylation

In the early 1950s it was found that progesterone is hydroxylated in the 11a-position by Rhizopus arrhizus and R. nigricans [25] and by Aspergillus niger [26]. This microbial reaction was an important breakthrough in partial synthesis of glucocorticoids because it allowed for the first time the functionalization of the non-activated C-11. The 11a-hydroxy steroids are of interest as intermediates in some cases, but the chemical transformation of the 11a-hydroxy group into the desired 11P-configuration is also possible by chemical means [23]. Biochemically, the best characterized are the steroid 11a-hydroxylase systems from the two Rhizopus species.

In the 1970s, Breskvar and Hudnik-Plevnik showed that the 11a-hydroxylase of R. nigricans is a cytochrome P450 enzyme by demonstrating the characteristic CO-difference spectrum with a maximum at 450 nm as well as the inhibtion of the enzyme by carbon monoxide; and this enzyme, together with the corresponding reductase, was subsequently shown to be microsomally located [27-29]. While in non-induced microsomal preparations the P450 content is very low (< 0.01 nmol mg-1 protein), after induction with progesterone it increases up to 1 nmol mg-1 protein. This inducing factor is remarkably high in comparison with the P450 increase measured in mammalian liver microsomes, but it is in the same range as in other microorganims [30]. Strains of Aspergillus, Curvularia, and Cunninghamella also catalyze the 11a-hydroxylation of progesterone, but the biochemical characterization of the corresponding enzymes is not nearly as complete as in the case of the Rhizopus species [23]. Both the composition of the essential components of the 11a-hydroxylase systems and their localization within the cell are unknown. Thus, a comparison of these enzymes with the Rhizopus 11a-hydroxylase on the basis of their specific activity is not yet possible.

More recently, Aspergillus fumigatus was reported to efficiently hydroxylate exogenous progesterone, producing 11a- and 15P-hydroxyprogesterone as major products, 7P-hydroxyprogesterone as a minor product and trace amounts of different dihydroxyprogesterones. However, upon prolonged incubation the dihy-droxyprogesterones were the sole metabolites in the culture medium. Biochemical analyses and ketoconazole inhibition studies suggested the presence of two non-inducible microsomal cytochromes P450, with one being a 7P-hydroxylase and the other a 11a-, 15P-hydroxylase [31].

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Heal Yourself With Qi Gong

Qigong also spelled Ch'i Kung is a potent system of healing and energy medicine from China. It's the art and science of utilizing breathing methods, gentle movement, and meditation to clean, fortify, and circulate the life energy qi.

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