Role of peroxisomes in human lipid metabolism and its importance for neurological development
Abstract
Peroxisomes play a crucial role in normal neurological development as exemplified by the devastating neurological consequences of a defect in the biogenesis of peroxisomes as in Zellweger syndrome. The underlying basis for the important role of peroxisomes in neurological development resides in the fact that peroxisomes catalyze a number of physiological functions, notably involving the metabolism of different lipids. Indeed, peroxisomes catalyse the beta-oxidative breakdown of certain fatty acids including: (1.) the very long-chain fatty acids C22:0, C24:0, and C26:0; (2.) pristanic acid and (3.) the bile acid intermediates di- and trihydroxycholestanoic acid which cannot be oxidized in mitochondria. Furthermore, peroxisomes catalyze the synthesis of a particular type of lipids, i.e. ether-linked phospholipids, which are highly abundant in brain, especially in myelin. The current state of knowledge with respect to the metabolic role of peroxisomes will be described in this paper with particular emphasis on the role of peroxisomes in brain.
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Most patients with acyl-CoA oxidase deficiency show neonatal onset of hypotonia, seizures, failure to thrive, hepatomegaly, psychomotor retardation, sensory deafness, absent reflexes, and visual loss with retinopathy and extinguished electroretinograms.
“Most patients show neonatal onset of hypotonia, seizures, failure to thrive, hepatomegaly, psychomotor retardation, sensory deafness, absent reflexes, and visual loss with retinopathy and extinguished electroretinograms [80].”
From Peroxisomes in brain development and function (2016) · cites this paper as [80]
Deficiency in FAR1 causes RCDP type 4.
“the disorder of three patients with a deficiency in FAR1, the gene coding for fatty acyl-CoA reductase 1, which generates the fatty alcohols necessary to form the ether bond of the 1-alkyl chain in ether phospholipid biosynthesis [183], was categorized as RCDP type 4 [80].”
From Peroxisomes in brain development and function (2016) · cites this paper as [80]
Two additional subtypes of RCDP were identified based on strong reduction of plasmalogen levels and similarity of symptoms with classical RCDP.
“Recently, two additional subtypes of RCDP were identified based on the strong reduction of plasmalogen levels in the patients and the similarity of their symptoms with “classical” RCDP.”
From Peroxisomes in brain development and function (2016) · cites this paper as [80]
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Peroxisomes in brain development and function
Berger, J., Dorninger, F., Forss-Petter, S., & Kunze, M. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.12.005 · Cited by 194 · see citing works
“First, the disorder of three patients with a deficiency in FAR1, the gene coding for fatty acyl-CoA reductase 1, which generates the fatty alcohols necessary to form the ether bond of the 1-alkyl chain in ether phospholipid biosynthesis [183], was categorized as RCDP type 4 [80].”
BackgroundBarøy, T., Koster, J., Strømme, P., Ebberink, M. S., Misceo, D., Ferdinandusse, S., Holmgren, A., Hughes, T., Merckoll, E., Westvik, J., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv305 · Cited by 81 · see citing works
Self-citation
- Authors
- Wanders, R. J. A., & Poll-The, B. T.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Wanders, Ronald J.A.
- ORCID
- Wanders, Ronald J.A.
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 637
- Pages
- 11-17
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W607611259
- Cited by
- 46
- References
- 66
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 7 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 6 · 2018: 4 · 2017: 5 · 2016: 3 · 2015: 3
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- peroxisomes, peroxisome biogenesis disorders, Zellweger syndrome, lipid metabolism, brain development, very long chain fatty acids, fatty acid beta-oxidation, pristanic acid, bile acid intermediates, ether phospholipids, myelin, brain
- MeSH terms
- Brain, Fatty Acids, Humans, Mitochondria, Oxidation-Reduction, Zellweger Syndrome, Peroxisomes, Lipid Metabolism
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