Hydride shift cholesterol biosynthesis

Comforth and his colleagues have investigated the stereochemistry of isomerization of isopentenyl to dimethylallyl pyrophosphate in isoprenoid biosynthesis. They find that the prototropic change involved is stereochemically different from the superficially analogous association of C5 units. Bisabolene appears to be excluded as an intermediate in the biosynthesis of helicobasidin and trichothecin by recent labelling studies (see also Vol. 1, p. 232, ref. 81) and a 1,4-hydride shift in the initially formed intermediate is indicated. The loss of the C-14 methyl group in cholesterol biosynthesis differs from loss of the C-4 methyl groups. The 32-carbon atom is released at the aldehyde oxidation level as formic acid. 

In green plants, which contain little or no cholesterol, cydoartenol is the key intermediate in sterol biosynthesis.161-1623 As indicated in Fig. 22-6, step c, cydoartenol can be formed if the proton at C-9 is shifted (as a hydride ion) to displace the methyl group from C-8. A proton is lost from the adjacent methyl group to close the cyclopropane ring. There are still other ways in which squalene is cyclized,162/163/1633 including some that incorporate nitrogen atoms and form alkaloids.1631 One pathway leads to the hop-anoids. These triterpene derivatives function in bacterial membranes, probably much as cholesterol does in our membranes. The three-dimensional structure of a bacterial hopene synthase is known.164 1643 Like glucoamylase (Fig. 2-29) and farnesyl transferase, the enzyme has an (a,a)6-barrel structure in one domain and a somewhat similar barrel in a second domain. 

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