The stereochemistry and enzymology of the β-oxidative biosynthesis of bile acids in rat liver peroxisomes

The emphasis of this present research is on the biosynthetic degradation of the cholesterol side chain. The first research is on the stereochemistry and enzymology of the ß-oxidative biosynthesis of bile acids in rat liver peroxisomes, and the second is the synthesis of ß-hydroxy-ℇ-N-Trimethyllysine, an intermediate in carnitine biosynthesis. The first project investigated the possible involvement of an ⍺-methylacyl-CoA racemase in an alternative pathway in bile acid biosynthesis. The results of the first project indicate that the (24S,25S)-3⍺, 7⍺, 12⍺,24ƹ-tetrahydroxy-5ß-cholestanoyl-CoA (24-OH-THCA-CoA) diastereomoer is epimerized at the ⍺-methyl position to the (24S,25R)-24-Oh-THCA-CoA diastereomoer, even though a hydroxyl group occupies the ß-position. Although the rate of epimerization is affected by the presence of a hydroxyl group, results have shown for the first time the possible existence of an alternative bile acid biosynthesis pathway, which explains the results from the analysis of the two human subjects with perMFE-2 deficiencyies that still were found to produce bile acids. The results of the second project confirm the synthesis and purification of ß-hydroxy-ℇ-N-Trimethyllysine as the dichloride salt