Abstract
Docosahexaenoic acid (DHA) circulates in mammals in lipoproteins and bound to serum albumin as a nonesterified fatty acid as well as esterified in lysophosphatidylcholine (lysoPC). 1-Lyso,2-DHA-glycerophosphocholine (GPC) is an unstable isomer because of a primary alcohol at the sn-1 position. To keep DHA at the sn-2 position of lysoPC, its usual position for the corresponding lysoPC to be acylated into PC in tissues, we synthesized 1-acetyl,2-DHA-GPC and confirmed its structure by use of nuclear magnetic resonance (NMR) spectroscopy in comparison with its positional isomer, 1-DHA,2-acetyl-GPC. 1-Lyso,2-DHA-GPC was prepared from 1-stearoyl,2-DHA-GPC by enzymatic hydrolysis and purified by high-performance liquid chromatography. The isomerization of 1-lyso,2-DHA-GPC into 1-DHA,2-lyso-GPC was obtained by keeping the former overnight at room temperature under nitrogen. Both lysoPC isomers were acetylated by acetic anhydride into 1-acetyl,2-DHA-GPC and 1-DHA,2-acetyl-GPC, respectively, and the resulting phospholipids were fully characterized by NMR. In particular, the 1,2 substitution pattern of the acetyl and DHA chains could be easily detected by 2D heteronuclear multibond correlation. We conclude that 1-acetyl,2-DHA-GPC might be considered as a stable form of 1-lyso,2-DHA-GPC for its delivery to tissues, if the latter exhibits acetyl hydrolase activity.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Abbreviations
- COSY:
-
correlation spectroscopy
- DHA:
-
docosahexaenoic acid
- GPC:
-
glycerophosphocholine
- HPLC:
-
high-performance liquid chromatography
- HMBC:
-
heteronuclear multibond correlation
- HSQC:
-
heteronuclear single quantum coherence
- lysoPC:
-
lysophosphatidylcholine
- NMR:
-
nuclear magnetic resonance
- PC:
-
phosphatidylcholine
- TLC:
-
thin-layer chromatography
References
Bang, H.O., Dyerberg, J., and Hjorne, N. (1976) The Composition of Food Consumed by Greenland Eskimos, Acta Med. Scand. 200, 69–73.
Leaf, A. (1990) Cardiovascular Effects of Fish Oils. Beyond the Platelet, Circulation 82, 624–628.
Anderson, R.E. (1970) Lipids of the Ocular Tissues. IV. A Compoarison of the Phospholipids from the Retina of Six Mammalian Species, Exp. Eye Res. 10, 339–344.
Salem, N., Jr., Kim, H.Y., and Yergey, J.A. (1986) Docosahexaenoic Acid Membrane Function and Metabolism, in Health Effects of Polyunsaturated Fatty Acid in Seafoods (Simopoulos, A.P., Kifer, R.P., and Martin, R., eds.), pp. 263–317, Academic Press, Orlando.
Neuringer, M., Connor, W.E., Lin, D.S., Barstad, L., and Luck, S.J. (1986) Biochemical and Functional Effects of Prenatal and Postnatal Omega-3 Fatty Acid Deficiency on Retina and Brain in Rhesus Monkeys, Proc. Natl. Acad. Sci. USA 83, 285–294.
Makrides, M., Neumann, M.A., and Gibson, R.A. (1996) Is Dietary Docosahexaenoic Acid Essential for Term Infants? Lipids 31, 115–119.
Werkman, S.H., and Carlson S.E. (1996) A Randomized Trial of Visual Attention of Preterm Infants Fed Docosahexanoic Acid Until Nine Months, Lipids 31, 91–97.
Croset, M., Brossard, N., Pachiaudi, C., Normand, S., Lecerf, J., Chirouze, V., Riou, J.P., Tayot, J.L., and Lagarde, M. (1996) In Vivo Compartmental Metabolism of 13C Docosahexaenoic Acid, Studied by Gas Chromatography-Combustion Isotope Ratio Mass Spectrophotometry, Lipids 31, 109–114.
Brossard, N., Croset, M., Lecerf, J., Pachaudi, C., Normand, S., Chirouze, V., Macovschi, O., Riou, J.P., Tayot, J.L., and Lagarde, M. (1996) Metabolic Fate of an Oral Dose of (13C) Docosahexaenoic Acid Triglyceride in the Rat, Am. J. Physiol. 270, R846-R854.
Lemaitre-Delaunay, D., Pachiaudi, C., Laville, M., Pousin, J., Armstrong, M., and Lagarde, M. (1999) Blood Compartmental Metabolism of Docosahexaenoic Acid (DHA) in Humans After Ingestion of a Single Dose of (13C)-Phosphatidylcholine Containing DHA, J. Lipid Res. 40, 1867–1874.
Innis, S.M., (1992) Plasma and Red Blood Cell Fatty Acid Values as Indexes of Essential Fatty Acid in the Developing Organs of Infants Fed with Milk or Formulas, J. Pediatr. 120, 578–586.
Thiès, F., Pillon, C., Molière, P., Lagarde, M., and Lecerf, J. (1994) Preferential Incorporation of sn-2 lysoPC DHA Over Unesterified DHA in the Young Rat Brain, Am. J. Physiol. 267, R1273-R1279.
Bernoud N., Fenart, L., Molière P., Dehouck, M.P., Lagarde, M., Cecchelli, R., and Lecerf, J. (1999) Preferential Transfer of 2-Docosahexaenoyl-1-lysophosphatidylcholine Through an in vitro Blood-Brain Barrier Over Unesterified Docosahexaenoic Acid, J. Neurochem. 72, 338–345.
Slotboom, A.J., De Hass, G.H., Burbach-Westerhuis, G.J., and Van Deenen, L.L.M. (1970) Hydrolysis of Phosphoglycerides by Purified Lipase Preparations. Preparation of Unsaturated 2-Monoacyl Choline Phosphoglycerides, Chem. Phys. Lipids 4, 30–36.
Bligh, E.G., and Dyer, W.J. (1959) A Rapid Method of Total Lipid Extraction and Purification, Can. J. Biochem. Physiol. 37, 911–917.
Thiès, F., Delachambre, M.C., Bentejac, M., Lagarde, M., and Lecerf, J. (1992) Unsaturated Fatty Acids Esterified in 2-Acyl-1-lysophosphatidylcholine Bound to Albumin Are More Efficiently Taken Up by the Young Rat Brain Than the Unesterified Form, J. Neurochem. 59, 1110–1116.
Croset, M., Brossard, N., Polette, A., and Lagarde, M. (1999) Characterization of Plasma Unsaturated Lysophosphatidylcholines in Human and Rat, Biochem. J., in press.
Robinson, B.S., Baisted, D.J., and Vance, D.E. (1989) Comparison of Albumin-Mediated Release of Lysophosphatidylcholine and Lysophosphatidylethanolamine from Cultured Rat Hepatocytes, Biochem. J. 264, 125–131.
Gunstone, F.D., and Seth, S. (1994) A Study of the Distribution of Eicosapentaenoic Acid and Docosahexaenoic Acid Between the α and β Glycerol Chains in Fish Oils by 13C-NMR Spectroscopy, Chem. Phys. Lipids 71, 119–126.
Sacchi, R., Medina, I., Aubourg, P.S., Giudicianni, I., Paolillo, L., and Addeo, F. (1993) Quantitative High-Resolution 13C NMR Analysis of Lipids Extracted from the White Muscle of Atlantic Tuna (Thunnus alalunga), J. Agric. Food Chem. 41, 1247–1253.
Haraldsson, G.G., Gudmundsson, B.Ö., and Almarsson, Ö. (1995) The Synthesis of Homogeneous Triglycerides of Eicosapentaenoic Acid and Docosahexaenoic Acid by Lipase, Tetrahedron 51, 941–952.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Polette, A., Deshayes, C., Chantegrel, B. et al. Synthesis of acetyl, docosahexaenoyl-glycerophosphocholine and its characterization using nuclear magnetic resonance. Lipids 34, 1333–1337 (1999). https://doi.org/10.1007/s11745-999-0486-1
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11745-999-0486-1