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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Jan 9;93(1):49–54. doi: 10.1073/pnas.93.1.49

Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants.

N Salem Jr 1, B Wegher 1, P Mena 1, R Uauy 1
PMCID: PMC40176  PMID: 8552667

Abstract

It is becoming clear that an adequate level of long-chain highly unsaturated fatty acids in the nervous system is required for optimal function and development; however, the ability of infants to biosynthesize long-chain fatty acids is unknown. This study explores the capacity of human infants to convert 18-carbon essential fatty acids to their elongated and desaturated forms, in vivo. A newly developed gas chromatography/negative chemical ionization/mass spectrometry method employing 2H-labeled essential fatty acids allowed assessment of this in vivo conversion with very high sensitivity and selectivity. Our results demonstrate that human infants have the capacity to convert dietary essential fatty acids administered enterally as 2H-labeled ethyl esters to their longer-chain derivatives, transport them to plasma, and incorporate them into membrane lipids. The in vivo conversion of linoleic acid (18:2n6) to arachidonic acid (20:4n6) is demonstrated in human beings. All elongases/desaturases necessary for the conversion of linolenic acid (18:3n3) to docosahexaenoic acid (22:6n3) are also active in the first week after birth. Although the absolute amounts of n-3 fatty acid metabolites accumulated in plasma are greater than those of the n-6 family, estimates of the endogenous pools of 18:2n6 and 18:3n3 indicate that n-6 fatty acid conversion rates are greater than those of the n-3 family. While these data clearly demonstrate the capability of infants to biosynthesize 22:6n3, a lipid that is required for optimal neural development, the amounts produced in vivo from 18:3n3 may be inadequate to support the 22:6n3 level observed in breast-fed infants.

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Selected References

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  1. Birch E. E., Birch D. G., Hoffman D. R., Uauy R. Dietary essential fatty acid supply and visual acuity development. Invest Ophthalmol Vis Sci. 1992 Oct;33(11):3242–3253. [PubMed] [Google Scholar]
  2. Bourre J. M., Francois M., Youyou A., Dumont O., Piciotti M., Pascal G., Durand G. The effects of dietary alpha-linolenic acid on the composition of nerve membranes, enzymatic activity, amplitude of electrophysiological parameters, resistance to poisons and performance of learning tasks in rats. J Nutr. 1989 Dec;119(12):1880–1892. doi: 10.1093/jn/119.12.1880. [DOI] [PubMed] [Google Scholar]
  3. Carlson S. E., Werkman S. H., Peeples J. M., Cooke R. J., Tolley E. A. Arachidonic acid status correlates with first year growth in preterm infants. Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):1073–1077. doi: 10.1073/pnas.90.3.1073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Emken E. A., Adlof R. O., Rakoff H., Rohwedder W. K., Gulley R. M. Human metabolic studies with deuterated alpha-linolenic acid. Nutrition. 1992 May-Jun;8(3):213–196. [PubMed] [Google Scholar]
  5. Emken E. A., Rohwedder W. K., Adlof R. O., Rakoff H., Gulley R. M. Metabolism in humans of cis-12,trans-15-octadecadienoic acid relative to palmitic, stearic, oleic and linoleic acids. Lipids. 1987 Jul;22(7):495–504. doi: 10.1007/BF02540365. [DOI] [PubMed] [Google Scholar]
  6. Hagve T. A., Christophersen B., Høie K., Johansen Y. Effect of a low fat diet on essential fatty acid metabolism in healthy human subjects. Scand J Clin Lab Invest Suppl. 1986;184:61–66. [PubMed] [Google Scholar]
  7. Hansen H. S., Jensen B. Essential function of linoleic acid esterified in acylglucosylceramide and acylceramide in maintaining the epidermal water permeability barrier. Evidence from feeding studies with oleate, linoleate, arachidonate, columbinate and alpha-linolenate. Biochim Biophys Acta. 1985 May 17;834(3):357–363. doi: 10.1016/0005-2760(85)90009-8. [DOI] [PubMed] [Google Scholar]
  8. Innis S. M. Essential fatty acids in growth and development. Prog Lipid Res. 1991;30(1):39–103. doi: 10.1016/0163-7827(91)90006-q. [DOI] [PubMed] [Google Scholar]
  9. Lefkowith J. B., Flippo V., Sprecher H., Needleman P. Paradoxical conservation of cardiac and renal arachidonate content in essential fatty acid deficiency. J Biol Chem. 1985 Dec 15;260(29):15736–15744. [PubMed] [Google Scholar]
  10. Leyton J., Drury P. J., Crawford M. A. Differential oxidation of saturated and unsaturated fatty acids in vivo in the rat. Br J Nutr. 1987 May;57(3):383–393. doi: 10.1079/bjn19870046. [DOI] [PubMed] [Google Scholar]
  11. Lucas A., Morley R., Cole T. J., Lister G., Leeson-Payne C. Breast milk and subsequent intelligence quotient in children born preterm. Lancet. 1992 Feb 1;339(8788):261–264. doi: 10.1016/0140-6736(92)91329-7. [DOI] [PubMed] [Google Scholar]
  12. Makrides M., Neumann M. A., Byard R. W., Simmer K., Gibson R. A. Fatty acid composition of brain, retina, and erythrocytes in breast- and formula-fed infants. Am J Clin Nutr. 1994 Aug;60(2):189–194. doi: 10.1093/ajcn/60.2.189. [DOI] [PubMed] [Google Scholar]
  13. Makrides M., Neumann M., Simmer K., Pater J., Gibson R. Are long-chain polyunsaturated fatty acids essential nutrients in infancy? Lancet. 1995 Jun 10;345(8963):1463–1468. doi: 10.1016/s0140-6736(95)91035-2. [DOI] [PubMed] [Google Scholar]
  14. Mead J. F. The non-eicosanoid functions of the essential fatty acids. J Lipid Res. 1984 Dec 15;25(13):1517–1521. [PubMed] [Google Scholar]
  15. Nakashima Y., Yuasa S., Hukamizu Y., Okuyama H., Ohhara T., Kameyama T., Nabeshima T. Effect of a high linoleate and a high alpha-linolenate diet on general behavior and drug sensitivity in mice. J Lipid Res. 1993 Feb;34(2):239–247. [PubMed] [Google Scholar]
  16. Neuringer M., Anderson G. J., Connor W. E. The essentiality of n-3 fatty acids for the development and function of the retina and brain. Annu Rev Nutr. 1988;8:517–541. doi: 10.1146/annurev.nu.08.070188.002505. [DOI] [PubMed] [Google Scholar]
  17. Neuringer M., Connor W. E., Lin D. S., Barstad L., Luck S. Biochemical and functional effects of prenatal and postnatal omega 3 fatty acid deficiency on retina and brain in rhesus monkeys. Proc Natl Acad Sci U S A. 1986 Jun;83(11):4021–4025. doi: 10.1073/pnas.83.11.4021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nichaman M. Z., Olson R. E., Sweeley C. C. Metabolism of linoleic acid-1-14-C in normolipemic and hyperlipemic humans fed linoleate diets. Am J Clin Nutr. 1967 Oct;20(10):1070–1083. doi: 10.1093/ajcn/20.10.1070. [DOI] [PubMed] [Google Scholar]
  19. Pawlosky R. J., Sprecher H. W., Salem N., Jr High sensitivity negative ion GC-MS method for detection of desaturated and chain-elongated products of deuterated linoleic and linolenic acids. J Lipid Res. 1992 Nov;33(11):1711–1717. [PubMed] [Google Scholar]
  20. Pawlosky R., Barnes A., Salem N., Jr Essential fatty acid metabolism in the feline: relationship between liver and brain production of long-chain polyunsaturated fatty acids. J Lipid Res. 1994 Nov;35(11):2032–2040. [PubMed] [Google Scholar]
  21. Poisson J. P., Dupuy R. P., Sarda P., Descomps B., Narce M., Rieu D., Crastes de Paulet A. Evidence that liver microsomes of human neonates desaturate essential fatty acids. Biochim Biophys Acta. 1993 Apr 7;1167(2):109–113. doi: 10.1016/0005-2760(93)90149-4. [DOI] [PubMed] [Google Scholar]
  22. Salem N., Jr, Ward G. R. Are omega 3 fatty acids essential nutrients for mammals? World Rev Nutr Diet. 1993;72:128–147. doi: 10.1159/000422334. [DOI] [PubMed] [Google Scholar]
  23. Uauy R. D., Birch D. G., Birch E. E., Tyson J. E., Hoffman D. R. Effect of dietary omega-3 fatty acids on retinal function of very-low-birth-weight neonates. Pediatr Res. 1990 Nov;28(5):485–492. doi: 10.1203/00006450-199011000-00014. [DOI] [PubMed] [Google Scholar]
  24. Uauy R., Birch E., Birch D., Peirano P. Visual and brain function measurements in studies of n-3 fatty acid requirements of infants. J Pediatr. 1992 Apr;120(4 Pt 2):S168–S180. doi: 10.1016/s0022-3476(05)81252-1. [DOI] [PubMed] [Google Scholar]
  25. de Gomez Dumm I. N., Brenner R. R. Oxidative desaturation of alpha-linoleic, linoleic, and stearic acids by human liver microsomes. Lipids. 1975 Jun;10(6):315–317. doi: 10.1007/BF02532451. [DOI] [PubMed] [Google Scholar]

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