Journal article
Catabolism of 4-hydroxyacids and 4-hydroxynonenal via 4-hydroxy-4-phosphoacyl-CoAs
The Journal of biological chemistry, Vol.284(48), pp.33521-33534
11/27/2009
Handle:
https://hdl.handle.net/2376/109964
PMCID: PMC2785196
PMID: 19759021
Abstract
4-Hydroxyacids are products of ubiquitously occurring lipid peroxidation (C(9), C(6)) or drugs of abuse (C(4), C(5)). 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 (C(4) to C(11)) 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 (31)P-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 beta-oxidation. The second and minor pathway involves a sequence of beta-oxidation, alpha-oxidation, and beta-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.
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Details
- Title
- Catabolism of 4-hydroxyacids and 4-hydroxynonenal via 4-hydroxy-4-phosphoacyl-CoAs
- Creators
- Guo-Fang Zhang - Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106, USARajan S KombuTakhar KasumovYong HanSushabhan SadhukhanJianye ZhangLawrence M SayreDale RayK Michael GibsonVernon A AndersonGregory P TochtropHenri Brunengraber
- Publication Details
- The Journal of biological chemistry, Vol.284(48), pp.33521-33534
- Academic Unit
- Pharmacotherapy, Department of
- Publisher
- United States
- Grant note
- R01 HD058553 / NICHD NIH HHS R33DK070291 / NIDDK NIH HHS R01 NS040270 / NINDS NIH HHS R33 DK070291 / NIDDK NIH HHS R01 ES013925 / NIEHS NIH HHS R01ES013925 / NIEHS NIH HHS
- Identifiers
- 99900547396301842
- Language
- English
- Resource Type
- Journal article