Identification of 7 α,24-Dihydroxy-3-oxocholest-4-en-26-oic and 7α,25-Dihydroxy-3-oxocholest-4-en-26-oic Acids in Human Cerebrospinal Fluid and Plasma.

Identification of 7α,24-Dihydroxy-3-oxocholest-4-en-26-oic and 7α,25-Dihydroxy-3-oxocholest-4-en-26-oic Acids in Human Cerebrospinal Fluid and Plasma.
Biochimie. 2018 Jun 27;:
Authors: Abdel-Khalik J, Crick PJ, Yutuc E, DeBarber AE, Duell PB, Steiner RD, Laina I, Wang Y, Griffiths WJ
Abstract
Dihydroxyoxocholestenoic acids are intermediates in bile acid biosynthesis. Here, using liquid chromatography - mass spectrometry, we confirm the identification of 7α,24-dihydroxy-3-oxocholest-4-en-26-oic and 7α,25-dihydroxy-3-oxocholest-4-en-26-oic acids in cerebrospinal fluid (CSF) based on comparisons to authentic standards and of 7α,12α-dihydroxy-3-oxocholest-4-en-26-oic and 7α,x-dihydroxy-3-oxocholest-4-en-26-oic (where hydroxylation is likely on C-22 or C-23) based on exact mass measurement and multistage fragmentation. Surprisingly, patients suffering from the inborn error of metabolism cerebrotendinous xanthomatosis, where the enzyme CYP27A1, which normally introduces the (25 R)26-carboxylic acid group to the sterol side-chain, is defective still synthesise 7α,24-dihydroxy-3-oxocholest-4-en-26-oic acid and also both 25 R- and 25 S-epimers of 7α,12α-dihydroxy-3-oxocholest-4-en-26-oic acid. We speculate that the enzymes CYP46A1 and CYP3A4 may have C-26 carboxylase activity to generate these acids. In patients suffering from hereditary spastic paraplegia type 5 the CSF concentrations of the 7α,24- and 7α,25-dihydroxy acids...

Source: Biochimie - June 27, 2018 Category: Biochemistry Authors: Abdel-Khalik J, Crick PJ, Yutuc E, DeBarber AE, Duell PB, Steiner RD, Laina I, Wang Y, Griffiths WJ Tags: Biochimie Source Type: research