Hydroxysteroids transformation

C-20 deduction. Two stereoisomers can result from this transformation, although cortisol is thought to act primarily with (R)20P-hydroxysteroid dehydrogenase. This is a first step in the metabohsm of corticosterone. 

Rahier and his co-workers also characterized the activities of a sterol C-4 methyl oxidase (SMO), a 4-carboxysterol-3-hydroxysteroid dehydrogenase/ C-4 decarboxylase (3-HSD/D) and an NADPH-dependent 3-oxosteroid reductase in order to define the steps involved in C-4 demethylation in plants (Pascal et al, 1993 Rondet et al, 1999). Only recently, they have isolated two cDNAs from Arabidopsis thaliana encoding bifunctional 3-HSD/D. Transformation of a yeast ergosterol auxotroph mutant, which lacks 3-HSD/D activity, with either of these cDNAs restored ergosterol biosynthesis in the yeast mutant (Rahier et al, 2006). 

Following Pasteur s work in the 1860s, which elucidated some roles of microbes in acetification (wine turning to vinegar), interest in microbial transformations slowly developed. By the end of the century several processes were in use. Even resolution of some racemates to obtain (at least one) optically pure enantiomer were viable procedures (e.g., lactic and mandelic acids). An observation that yeast (in fermentations) is capable of reducing 17-ketosteroids to 17(3-hydroxysteroids in the late 1930s ultimately led to a search for other microbially mediated chemical transformations. 

Besides the involvement in the de novo biosynthesis of BH4, SR may also participate in the pterin salvage pathway by catalyzing the conversion of sepiapterin (Figure 14, 47) into 7,8-dihydrobiopterin (46) that is then transformed to BH4 by dihydrofolate reductase (DHFR EC 1.5.1.3). Both reactions consume NADPH. Although SR is sufficient to complete the BH4 biosynthesis, a family of alternative NADPH-dependent aldo—keto reductases, including carbonyl reductases (CR), aldose reductases (AR), and the 3a-hydroxysteroid dehydrogenase type 2 (AKR1C3) may participate in the diketo reduction of the carbonyl side chain in Moreover, based on the discover) of the autosomal recessive deficiency for SR, which presents... 

The natural series of steroids is not necessarily the preferred substrate for aU microorganisms. Greenspan and collaborators (Ap-28) have described oxidation of 17 -hydroxysteroids with Flavobacterium dehydrogenans and -dehydrogenations with Corynebacterium hoagii, which resulted in the transformation of both d and I substrates. 

The next major step in the transformation of cholesterol to cholic acid is the conversion of the 5-choles-tene-3j8, 7a-diol into 7a-hydroxy-4-cholestene-3-one. Such conversion may occur through at least two different pathways. In the first, the substrate (5-choles-tene-3j8, 7a-diol) is sequentially attacked by a microsomal 3j8-hydroxysteroid dehydrogenase and then... 

The transformations of the 3,3-hydroxy-5a acids will not be reviewed here, since little information is available. Adequate evidence for an active 3,3-hydroxysteroid dehydrogenase of rat liver is at hand (165, 166,167). 

After the first demonstration of a direct metabolism of a steroid conjugate [androstenediol sulfate =i dehydroepiandrosterone sulfate (Baulieu et ah, 1963)], showing that a 17j8-hydroxysteroid oxidoreductase can have a sulfo conjugate as a substrate, other enzymic transformations of dehydroepiandrosterone sulfate were reported (Fig. 4). Dehydroepiandrosterone sulfate can undergo 16o -hydroxylation to 16a-hydroxy-dehydroepiandrosterone sulfate which can be further hydroxylated into androstenetriol sulfate its direct 17-hydroxylated metabolite, androstene-... 

This cascade radical rearrangement to the esters, followed by cychzation to cyclic ethers, comprises a new method of transforming hydroxy steroids into oxasteroids under essentially neutral conditions. A number of hydroxysteroids have been converted into oxasteroids. Another example is outlined in Scheme 42. ... 

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