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DES2 protein is responsible for phytoceramide biosynthesis in the mouse small intestine
Open accessAbstract
The C-4 hydroxylation of sphinganine and dihydroceramide is a rate-limiting reaction in the biosynthesis of phytosphingolipids. Mouse DES1 (MDES1) cDNA homologous to the Drosophila melanogaster degenerative spermatocyte gene-1 (des-1) cDNA leads to sphingosine Δ4-desaturase activity, and another mouse homologue, MDES2, has bifunctional activity, producing C-4 hydroxysphinganine and Δ4-sphingenine in yeast [Ternes, Franke, Zahringer, Sperling and Heinz (2002) J. Biol. Chem. 277, 25512–25518]. Here, we report the characterization of mouse DES2 (MDES2) using an in vitro assay with a homogenate of COS-7 cells transfected with MDES2 cDNA and N-octanoyl-sphinganine and sphinganine as substrates. MDES2 protein prefers dihydroceramide as a substrate to sphinganine, and exhibits dihydroceramide Δ4-desaturase and C-4 hydroxylase activities. MDES2 mRNA content was high in the small intestine and abundant in the kidney. In situ hybridization detected signals of MDES2 mRNA in the crypt cells. Immunohistochemistry using an anti-MDES2 peptide antibody stained the crypt cells and the adjacent epithelial cells. These results suggest that MDES2 is the dihydroceramide C-4 hydroxylase responsible for the biosynthesis of enriched phytosphingoglycolipids in the microvillous membranes of intestinal epithelial cells.
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“Sphingosine-and phytosphingosine-type ceramides are generated either via desaturation between the 4 and 5 positions of the LCB moiety of dihydroceramides (DS ceramides) by the desaturase DEGS1, or via hydroxylation of the same moiety at the 4 position by the hydroxylase DEGS2 (49,50).”
From Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS/MS (2020) · cites this paper as [49]
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Metadata
- Authors
- OMAE, F., MIYAZAKI, M., ENOMOTO, A., SUZUKI, M., SUZUKI, Y., & SUZUKI, A.
- Affiliations
- RIKEN (JP)
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2004-05-01
- Volume
- 379
- Issue
- 3
- Pages
- 687-695
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1224108
- OpenAlex
- W2103244006
- Cited by
- 118
- References
- 44
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 11 · 2022: 8 · 2021: 6 · 2020: 4 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 7 · 2015: 6 · 2014: 6 · 2013: 6 · 2012: 3
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Tokyo Medical and Dental University
- RIKEN
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
- Keywords
- small intestine, intestinal epithelial cells, crypt cells, sphinganine, dihydroceramide
- MeSH terms
- Animals, Cell Extracts, Ceramides, Mixed Function Oxygenases, Immunohistochemistry, Intestine, Small, Membrane Proteins, Multienzyme Complexes, Organ Specificity, Oxidoreductases, RNA, Messenger, Sphingosine, Transfection, In Situ Hybridization, COS Cells, Fatty Acid Desaturases, Mice
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