Acyl coenzyme A dependent retinol esterification by acyl coenzyme A:diacylglycerol acyltransferase 1
Abstract
We provide biochemical evidence that enzymes involved in the synthesis of triacylglycerol, namely acyl coenzyme A:diacylglycerol acyltransferase (DGAT) and acyl coenzyme A:monoacylglycerol acyltransferase (MGAT), are capable of carrying out the acyl coenzyme A:retinol acyltransferase (ARAT) reaction. Among them, DGAT1 appears to have the highest specific activity. The apparent K(m) values of recombinant DGAT1/ARAT for retinol and palmitoyl coenzyme A were determined to be 25.9+/-2.1 microM and 13.9+/-0.3 microM, respectively, both of which are similar to the values previously determined for ARAT in native tissues. A novel selective DGAT1 inhibitor, XP620, inhibits recombinant DGAT1/ARAT at the retinol recognition site. In the differentiated Caco-2 cell membranes, XP620 inhibits approximately 85% of the Caco-2/ARAT activity indicating that DGAT1/ARAT may be the major source of ARAT activity in these cells. Of the two most abundant fatty acyl retinyl esters present in the intact differentiated Caco-2 cells, XP620 selectively inhibits retinyl-oleate formation without influencing the retinyl-palmitate formation. Using this inhibitor, we estimate that approximately 64% of total retinyl ester formation occurs via DGAT1/ARAT. These studies suggest that DGAT1/ARAT is the major enzyme involved in retinyl ester synthesis in Caco-2 cells.
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DGAT1 depends on a pre-activated form of fatty acid carried by acyl-CoA.
“whereas DGAT1 depends on a pre-activated form of fatty acid carried by acyl-CoA [41].”
From Molecular Basis for Vitamin A Uptake and Storage in Vertebrates (2016) · cites this paper as [41]
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“LRAT catalyzes the transesterification of retinol utilizing a fatty acyl moiety present in the sn‐1 position of phosphatidylcholine [38–40], whereas DGAT1 depends on a pre‐activated form of fatty acid carried by acyl‐CoA [41].”
Background
- Authors
- Orland, M. D., Anwar, K., Cromley, D., Chu, C.-H., Chen, L., Billheimer, J. T., Hussain, M. M., & Cheng, D.
- Affiliations
- Bristol-Myers Squibb (United States) (US)
- SUNY Downstate Health Sciences University (US)
- Corresponding author
- Cheng, Dong
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 1737
- Issue
- 1
- Pages
- 76-82
- ISSN
- 1388-1981 (ISSN-L)
- OpenAlex
- W2007884452
- Cited by
- 97
- References
- 4
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 8 · 2021: 5 · 2020: 2 · 2019: 5 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 5 · 2013: 7 · 2012: 3
- FWCI
- 3.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- DGAT1, retinol esterification, retinyl palmitate, enzyme inhibition, Caco-2 cells, vitamin A metabolism, diacylglycerol acyltransferase, triglyceride synthesis
- MeSH terms
- Acyltransferases, Animals, Heterocyclic Compounds, 1-Ring, Humans, Kinetics, Vitamin A, Caco-2 Cells, Diacylglycerol O-Acyltransferase, Retinol O-Fatty-Acyltransferase
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