Generation of cholesterol carboxyaldehyde by the reaction of singlet molecular oxygen [O2 (1Delta(g))] as well as ozone with cholesterol.
A few years ago, it was reported that ozone is produced in human atherosclerotic arteries, on the basis of the identification of 3beta-hydroxy-5-oxo-5,6-secocholestan-6-al and 3beta-hydroxy-5beta-hydroxy-B-norcholestane-6beta-carboxaldehyde (ChAld) as their 2,4-dinitrophenylhydrazones. The formation of endogenous ozone was attributed to water oxidation catalyzed by antibodies, with the formation of dihydrogen trioxide as a key intermediate. We now report that ChAld is also generated by the reaction of cholesterol with singlet molecular oxygen [O2 (1Delta(g))] that is produced by photodynamic action or by the thermodecomposition of 1,4-dimethylnaphthalene endoperoxide, a defined pure chemical source of O2 (1Delta(g)). On the basis of 18O-labeled ChAld mass spectrometry, NMR, light emission measurements, and derivatization studies, we propose that the mechanism of ChAld generation involves the formation of the well-known cholesterol 5alpha-hydroperoxide (5alpha-OOH) (the major product of O2 ((1)Delta(g))-oxidation of cholesterol) and/or a 1,2-dioxetane intermediate formed by O2 (1Delta(g)) attack at the Delta(5) position. The Hock cleavage of 5alpha-OOH (the major pathway) or unstable cholesterol dioxetane decomposition (a minor pathway, traces) gives a 5,6-secosterol intermediate, which undergoes intramolecular aldolization to yield ChAld. These results show clearly and unequivocally that ChAld is generated upon the reaction of cholesterol with O2 (1Delta(g)) and raises questions about the role of ozone in biological processes.
Departamento de Bioquímica, Instituto de Química, Universidade de Sao Paulo, CP26077, CEP 05513-970, Sao Paulo, SP, Brazil.
Miriam
M
Uemi
Graziella E
GE
Ronsein
Sayuri
S
Miyamoto
Marisa H G
MH
Medeiros
Paolo
P
Di Mascio
D002784:Cholesterol / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010126:Ozone / Q000737:chemistry / Q000378:metabolism*; D026082:Singlet Oxygen / Q000737:chemistry / Q000378:metabolism*; D013261:Sterols / Q000737:chemistry / Q000378:metabolism
C479527:5,6-secosterol; D013261:Sterols; D026082:Singlet Oxygen; D010126:Ozone; C002843:cholesterol hydroperoxide; D002784:Cholesterol