Elongation, desaturation, and esterification of essential fatty acids by fetal rat brain in vivo.
Tracer amounts of either [1-14C]linolenic (18:3n-3, LNA), or [1-14C]linoleic (18:2n-6, LA) acids were intracranially injected into 19- to 20-day-old rat fetuses, and the time course of the in vivo formation and esterification of their long chain polyenoic metabolites was determined for up to 20 h. A rapid disappearance of free LNA and LA, with apparent half-lives of 60 and 40 min, respectively, was noticed. One hour after LNA injection, 32.3% and 14.3% of the total brain radioactivity was found in the neutral glyceride (NG) and phospholipid (PL) fractions, respectively. After 20 h, PL radioactivity attained a level of 75%. Phosphatidylcholine (PC), diacylglycerol (DG), and triacylglycerol (TG) constituted 40%, 23%, and 9% of the total brain label at 1 h, and 35%, 10% and 14% at 20 h, respectively. Ethanolamine-containing PL (including plasmalogen) radioactivity accounted for about 10% up to 6 h and increased nearly 3-fold at 20 h, primarily due to an increase in the amount of labeled docosapentaenoic and docosahexaenoic acids (DHA), the elongation-desaturation products of LNA. A similar pattern of incorporation into NG and PL fraction was observed after the administration of [1-14C]LA. After 1 h, PC, DG, and TG species constituted 23%, 10%, and 23% of the total brain radioactivity, whereas after 20 h it accounted for 44%, 6%, and 10%, respectively. Although radioactivity in the ethanolamine PL also increased substantially from 4% at 1 h to 29% at 20 h, the main labeled fatty acid in this fraction was LA. Labeled arachidonic acid (AA) constituted 42.7% of the total radioactivity in phosphatidylinositol (PI) at 20 h. At this time, it comprised 12.5% and 14% of the total radioactivity in PC and ethanolamine PL, respectively, suggesting a high degree of esterification selectivity. Comparison of the total amounts of LA and LNA and their corresponding labeled AA and DHA metabolites in brain and liver after 3 and 6 h indicated that the contribution of liver metabolism to the elongation-desaturation under these conditions was negligible. One hour after intracerebral injection of [3H]DHA (22:6n-3) or [3H]AA (20:4n-6), 29.2% and 12% of total radioactivity, respectively, was found in the ethanolamine PL while 20% and 40% was incorporated in PC, respectively. PI labeling by [3H]AA was 6- to 8-fold higher than that seen in the presence of DHA. A high percent of radioactivity (26.9% and 18.2%) was found in DG and TG species.(ABSTRACT TRUNCATED AT 400 WORDS)
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Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
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D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004281:Docosahexaenoic Acids / Q000378:metabolism; D004951:Esterification; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D000081031:Fatty Acid Elongases; D005228:Fatty Acids, Essential / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005989:Glycerides / Q000378:metabolism; D007700:Kinetics; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D017962:alpha-Linolenic Acid / Q000378:metabolism
D005228:Fatty Acids, Essential; D005230:Fatty Acids, Nonesterified; D005989:Glycerides; D008041:Linoleic Acids; D010743:Phospholipids; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D019787:Linoleic Acid; D044943:Fatty Acid Desaturases; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases