Propagation rate constants for the peroxidation of sterols on the biosynthetic pathway to cholesterol.
The free radical chain autoxidation of cholesterol and the oxidation products formed, i.e. oxysterols, have been the focus of intensive study for decades. The peroxidation of sterol precursors to cholesterol such as 7-dehydrocholesterol (7-DHC) and desmosterol as well as their oxysterols has received less attention. The peroxidation of these sterol precursors can become important under circumstances in which genetic conditions or exposures to small molecules leads to an increase of these biosynthetic intermediates in tissues and fluids. 7-DHC, for example, has a propagation rate constant for peroxidation some 200 times that of cholesterol and this sterol is found at elevated levels in a devastating human genetic condition, Smith-Lemli-Opitz syndrome (SLOS). The propagation rate constants for peroxidation of sterol intermediates on the biosynthetic pathway to cholesterol were determined by a competition kinetic method, i.e. a peroxyl radical clock. In this work, propagation rate constants for lathosterol, zymostenol, desmosterol, 7-dehydrodesmosterol and other sterols in the Bloch and Kandutsch-Russell pathways are assigned and these rate constants are related to sterol structural features. Furthermore, potential oxysterols products are proposed for sterols whose oxysterol products have not been determined.
Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA.
Connor R
CR
Lamberson
Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA.
Hubert
H
Muchalski
Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA.
Kari B
KB
McDuffee
Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA.
Keri A
KA
Tallman
Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA.
Libin
L
Xu
Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA. Electronic address: n.porter@vanderbilt.edu.
Ned A
NA
Porter
D002784:Cholesterol / Q000096:biosynthesis* / Q000737:chemistry; D007700:Kinetics; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010545:Peroxides / Q000737:chemistry / Q000378:metabolism; D013261:Sterols / Q000737:chemistry / Q000378:metabolism*
D010545:Peroxides; D013261:Sterols; C049375:perhydroxyl radical; D002784:Cholesterol
Free radicals; Oxysterols; Peroxidation; Radical clock; Rate constants; Sterols