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 ha s been described in isolated rat hepatocytes and human fibroblasts. Th is alternative pathway, which is independent of Delta(4) desaturation, involves elongation of C22:5 omega 3 and C22:4 omega 6 to C24 fatty a cids, Delta(6) desaturation of the C24 fatty acids and subsequent beta oxidation of the desaturated products to C22:6 omega 3 and C22:5 omeg a 6. To determine whether this alternative pathway is operative in the human infant and also to obtain additional information concerning end ogenous conversion of C18:3 omega 3 and C18:2 omega 6 to longer chain more unsaturated fatty acids, presence of [M + 18] isotopomers of omeg a 3 and omega 6 fatty acids in the plasma phospholipid fraction of ter m and preterm infants after administration of [U-C-13]18:3 omega 3 and [U-C-13]18:2 omega 6 was determined by negative chemical ionization g as chromatography/mass spectrometry. [M + 18] isotopomers of the follo wing omega 3 fatty acids were detected: C18:3, C18:4, C20:3, C20:4, C2 0:5, 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 t o detect [M + 18] isotopomers of C22 and C24 omega 6 fatty acids. Pres ence of [M + 18] isotopomers of C24:5 omega 3 and C24:60 omega 3 indic ates that these fatty acids were synthesized endogenously from C18:3 o mega 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 can not be excluded. Detection of [M + 18] isotopomers of C20:3 omega 3, C 20:2 omega 6, and C22:4 omega 3 suggests that C18:3 omega 3, C18:2 ome ga 6, and C20:4 omega 3 are elongated as well as desaturated. The spec ific fate of these elongation products and their importance in endogen ous synthesis of omega 3 and omega 6 long chain polyunsaturated fatty acids remain to be determined.