Journal ArticleDOI
Omega-oxidation of monocarboxylic acids in rat brain.
TLDR
The results demonstrate that the omega-oxidative pathway is prominent in brain and could play a role in brain fatty acid metabolism.Abstract:
The accumulation of dicarboxylic acids is a prominent feature of inborn and toxin induced disorders of fatty acid metabolism which are characterized by impaired mental status. The formation of dicarboxylic acids is also a critical step in liver in the induction of intracellular fatty acid binding proteins and the proliferation of peroxisomes. In order to understand what potential roles dicarboxylic acids have in brain, we examined the extent of omega-oxidation in rat brain. Homogenates of rat brain catalyze the omega-oxidation of monocarboxylic acids with a specific activity of between 0.87 and 5.23 nmol/mg of post-mitochondrial protein/h, depending on the substrate. The activity is remarkably high, between one-fourth and 4 times the activity found in rat liver, depending on the chain length of the substrate. Specific activity increases with increasing chain length of the substrate. The omega-oxidation of palmitic acid is linear over a range of 0.125-3.0 mg of protein and 5-50 microM substrate for up to 45 minutes of incubation. The product of omega-oxidation in brain is almost exclusively dicarboxylic acid. Cultured rat neurons, astrocytes, and oligodendrocytes all contain omega-oxidation activity. Western blots of rat brain homogenate demonstrate a protein that is recognized by antibody to rat liver CYP4A omega-hydroxylase. These results demonstrate that the omega-oxidative pathway is prominent in brain and could play a role in brain fatty acid metabolism.read more
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Journal ArticleDOI
Lipidomic Analysis of α-Synuclein Neurotoxicity Identifies Stearoyl CoA Desaturase as a Target for Parkinson Treatment
Saranna Fanning,Saranna Fanning,Aftabul Haque,Thibaut Imberdis,Valeriya Baru,M. Inmaculada Barrasa,Silke Nuber,Daniel Termine,Nagendran Ramalingam,Gary P.H. Ho,Tallie Noble,Jackson Sandoe,Yali Lou,Dirk Landgraf,Yelena Freyzon,Gregory A. Newby,Frank Soldner,Elizabeth Terry-Kantor,Tae-Eun Kim,Harald F. Hofbauer,Michel Becuwe,Rudolf Jaenisch,David Pincus,Clary B. Clish,Tobias C. Walther,Robert V. Farese,Supriya Srinivasan,Supriya Srinivasan,Michael A. Welte,Sepp D. Kohlwein,Ulf Dettmer,Susan Lindquist,Dennis J. Selkoe +32 more
TL;DR: Monounsaturated fatty acid metabolism is pivotal for αS-induced neurotoxicity, and inhibiting SCD represents a novel PD therapeutic approach.
Journal ArticleDOI
Structural Determination of the Substrate Specificities and Regioselectivities of the Rat and Human Fatty Acid ω-Hydroxylases
TL;DR: The fact that none of the rat and human CYP4A enzymes exhibits a high activity with arachidonic acid appears to limit their role as catalysts for the physiologically important conversion of arachidsonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE).
Journal ArticleDOI
Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in humans: CYP4F3B is the prominent player in PUFA metabolism.
Maude Fer,Laurent Corcos,Laurent Corcos,Yvonne Dréano,Emmanuelle Plée-Gautier,Jean-Pierre Salaün,Jean-Pierre Salaün,François Berthou,Yolande Amet +8 more
TL;DR: In this article, the authors showed that the ω9 and ω3 PUFAs (ETA, AA, EPA, and DHA) could all be used as alternative substrates in AA metabolism by human CYP4F2 and -4F3B enzymes.
Lipidomic Analysis of α-Synuclein Neurotoxicity Identifies Stearoyl CoA Desaturase as a Target for Parkinson Treatment
Saranna Fanning,Saranna Fanning,Aftabul Haque,Thibaut Imberdis,Valeriya Baru,M. Inmaculada Barrasa,Silke Nuber,Daniel Termine,Nagendran Ramalingam,Gary P.H. Ho,Tallie Noble,Jackson Sandoe,Yali Lou,Dirk Landgraf,Yelena Freyzon,Gregory A. Newby,Frank Soldner,Elizabeth Terry-Kantor,Tae-Eun Kim,Harald F. Hofbauer,Michel Becuwe,Rudolf Jaenisch,David Pincus,Clary B. Clish,Tobias C. Walther,Robert V. Farese,Supriya Srinivasan,Supriya Srinivasan,Michael A. Welte,Sepp D. Kohlwein,Ulf Dettmer,Susan Lindquist,Dennis J. Selkoe +32 more
TL;DR: In this paper, the authors investigated how alterations in α-synuclein or lipid/fatty acid homeostasis affect each other, and found that excess oleic acid (OA, 18:1) caused αS inclusion formation, which was reversed by SCD inhibition.
Journal ArticleDOI
Mouse models for peroxisome biogenesis defects and β-oxidation enzyme deficiencies.
TL;DR: A panel of mouse models has been created in which genes crucial to these processes were inactivated and the ensuing pathologies studied, allowing to document in detail histological abnormalities, metabolic and gene expression deregulations some of which are mediated by PPARα.
References
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