Intermediates in endogenous synthesis of C22:6 omega 3 and C20:4 omega 6 by term and preterm infants.
An alternative pathway of omega 3 and omega 6 fatty acid metabolism has been described in isolated rate hepatocytes and human fibroblasts. This alternative pathway, which is independent of delta 4 desaturation, involves elongation of C22 5 omega 3 and C22:4 omega 6 to C24 fatty acids, delta 6 desaturation of the C24 fatty acids and subsequent beta oxidation of the desaturated products to C22:6 omega 3 and C22:5 omega 6. To determine whether this alternative pathway is operative in the human infant and also to obtain additional information concerning endogenous conversion of C18:3 omega 3 and C18:2 omega 6 to longer chain more unsaturated fatty acids, presence of [M + 18] isotopomers of omega 3 and omega 6 fatty acids in the plasma phospholipid fraction of term and preterm infants after administration of [U-13C]18:3 omega 3 and [U-13C]18:2 omega 6 was determined by negative chemical ionization gas chromatography/mass spectrometry. [M + 18] isotopomers of the following omega 3 fatty acids were detected: C18:3, C18:4, C20:3, C20:4, C20:5, C22:4, C22:5, C22:6, C24:4 (two infants only), C24:5, and C24:6. [M + 18] isotopomers of omega 6 fatty acids detected included only C18:2, C18:3, C20:2, C20:3, and C20:4, but sensitivity was insufficient to detect [M + 18] isotopomers of C22 and C24 omega 6 fatty acids. Presence of [M + 18] isotopomers of C24:5 omega 3 and C24:6 omega 3 indicates that these fatty acids were synthesized endogenously from C18:3 omega 3. This plus the in vitro data strongly suggests that infants use the recently described alternative pathway in endogenous synthesis of C22:6 omega 3. However, involvement also of delta 4 desaturation cannot be excluded. Detection of [M + 18] isotopomers of C20:3 omega 3, C20:2 omega 6, and C22:4 omega 3 suggests that C18:3 omega 3, C18:2 omega 6, and C20:4 omega 3 are elongated as well as desaturated. The specific fate of these elongation products and their importance in endogenous synthesis of omega 3 and omega 6 long chain polyunsaturated fatty acids remain to be determined.
Sauerwald
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TU
USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Houston, Texas 77030, USA.
Hachey
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Jensen
C L
CL
Chen
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H
Anderson
R E
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Heird
W C
WC
D016718:Arachidonic Acid / Q000096:biosynthesis*; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn / Q000378:metabolism*; D007234:Infant, Premature / Q000378:metabolism*; D010743:Phospholipids / Q000097:blood
D005227:Fatty Acids; D010743:Phospholipids; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid