The stereochemistry and enzymology of the B-oxidative biosynthesis of bile acids in rat liver peroxisomes, and synthesis of B-hydroxy-E-N-trimethyllysine, an intermediate in carnitine biosynthesis

The emphasis of this present research is two fold. The first project is on the biosynthetic degradation of the cholesterol side chain, and the second is the synthesis of ß-hydroxy-ε-N-trimethyllysine, an intermediate in carnitine biosynthesis. The first project investigated the possible involvement of an α-methylacyl-CoA racemase in an alternative pathway in bile acid biosynthesis. The results of the first project indicate that the (24S,25S)-3α, 12α, 24ξ-tetrahydroxy-5β-cholestanoyl-CoA (24-OH-THCA-CoA) diastereomer is epimerized at the α-methyl position to the (24S,25R)-24-OH-THCA-CoA diastereomer, even though a hydroxyl group occupies the β-position. Although the rate of epimerization is effected 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 deficiency\u27s that still were found to produce bile acids. The results of the second project confirm the synthesis and purification of ß-hydroxy-ε-N-trimethyllysine as the dichloride salt