Catabolism of 4-hydroxyacids and 4-hydroxynonenal via 4-hydroxy-4-phosphoacyl-CoAs
Document Type
Article
Publication Date
11-27-2009
Abstract
4-Hydroxyacids are products of ubiquitously occurring lipid peroxidation (C9, C6) or drugs of abuse (C4, C5). We investigated the catabolism of these compounds using a combination of metabolomics and mass isotopomer analysis. Livers were perfused with various concentrations of unlabeled and labeled saturated 4-hydroxyacids (C4 to C11) or 4-hydroxynonenal. All the compounds tested form a new class of acyl-CoA esters, 4-hydroxy-4-phosphoacyl-CoAs, characterized by liquid chromatography-tandem mass spectrometry, accurate mass spectrometry, and 31P-NMR. All 4-hydroxyacids with five or more carbons are metabolized by two new pathways. The first and major pathway, which involves 4-hydroxy-4-phosphoacyl-CoAs, leads in six steps to the isomerization of 4-hydroxyacyl-CoA to 3-hydroxyacyl-CoAs. The latter are intermediates of physiological β-oxidation. The second and minor pathway involves a sequence of β-oxidation, β-oxidation, and β-oxidation steps. In mice deficient in succinic semialdehyde dehydrogenase, high plasma concentrations of 4-hydroxybutyrate result in high concentrations of 4-hydroxy-4-phospho-butyryl-CoA in brain and liver. The high concentration of 4-hydroxy-4-phospho-butyryl-CoA may be related to the cerebral dysfunction of subjects ingesting 4-hydroxybutyrate and to the mental retardation of patients with 4-hydroxybutyric aciduria. Our data illustrate the potential of the combination of metabolomics and mass isotopomer analysis for pathway discovery. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
Publication Title
Journal of Biological Chemistry
Recommended Citation
Zhang, G.,
Kombu, R.,
Kasumov, T.,
Han, Y.,
Sadhukhan, S.,
Zhang, J.,
Sayre, L.,
Ray, D.,
Gibson, K.,
Anderson, V.,
Tochtrop, G.,
&
Brunengraber, H.
(2009).
Catabolism of 4-hydroxyacids and 4-hydroxynonenal via 4-hydroxy-4-phosphoacyl-CoAs.
Journal of Biological Chemistry,
284(48), 33521-33534.
http://doi.org/10.1074/jbc.M109.055665
Retrieved from: https://digitalcommons.mtu.edu/michigantech-p/9054