title: A minimally invasive technique for the evaluation of the regulatory steps of the two major pathways of bile acid synthesis.
abstract: BACKGROUND
  Bile acid synthesis accounts for more than 95% of total cholesterol catabolism per day. We have developed a minimally invasive technique in humans that quantifies the rates of plasma appearance of 7alpha- and 27-hydroxycholesterol, representing the first steps of the "classical" and "alternative" pathways of bile acid synthesis, respectively.
  
  
  METHODS
  For this purpose, during the intravenous infusion of synthetic deuterated isotopomers of 7alpha-hydroxycholesterol and 27-hydroxycholesterol plasma samples are collected and analysed by a GC-MS based method that allows to quantify the exogenous/natural isotopomer ratio of the two sterols. From this data, the rates of plasma appearance of 7alpha- and 27-hydroxycholesterol are calculated.
  
  
  RESULTS
  In a group of healthy individuals steady state kinetics are obtained during a 2 h period yielding mean values of 2.0+/-0.8 and 3.7+/-0.6 mg/h for 7alpha- and 27-hydroxycholesterol, respectively. The data are consistent with findings using older techniques that require studies over several days.
  
  
  CONCLUSIONS
  Considering that at steady state of the exogenous/natural isotopomer ratio the plasma appearance of the two regulatory hydroxysterols are related to the rate of bile acid synthesis via the "classical" and the "alternative" pathways, respectively, the proposed method could be used to evaluate the immediate effects of different diets and drugs and other determinants on cholesterol catabolism.
authors.affiliation: Dipartimento di Medicina Sperimentale, Ambientale e Biotecnologie Mediche (DIMESAB), University of Milano-Bicocca, Via Cadore 48, 20052 Monza, Italy. marina.delpuppo@unimib.it
authors.forename: Marina
authors.initials: M
authors.lastname: Del Puppo
authors.forename: Andrea
authors.initials: A
authors.lastname: Crosignani
authors.forename: Matteo
authors.initials: M
authors.lastname: Longo
authors.forename: Massimo
authors.initials: M
authors.lastname: Zuin
authors.forename: Mauro
authors.initials: M
authors.lastname: Podda
authors.forename: Giovanni
authors.initials: G
authors.lastname: Galli
authors.forename: Emma
authors.initials: E
authors.lastname: De Fabiani
authors.forename: Pierangela
authors.initials: P
authors.lastname: Ciuffreda
authors.forename: Enzo
authors.initials: E
authors.lastname: Santaniello
authors.forename: Norman B
authors.initials: NB
authors.lastname: Javitt
authors.forename: Marzia Galli
authors.initials: MG
authors.lastname: Kienle
mesh_terms: D000328:Adult; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D003903:Deuterium; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male
chemical_list: D001647:Bile Acids and Salts; D006888:Hydroxycholesterols; C011724:cholest-5-en-3 beta,7 alpha-diol; C076996:27-hydroxycholesterol; D003903:Deuterium