Metabolism of linolenic acid and docosahexaenoic acid in rat retinas and rod outer segments.
Docosahexaenoic acid (22:6 omega 3) is uniquely enriched in photoreceptor outer segment phospholipids, comprising up to one-half of the fatty acids of phosphatidylethanolamine and phosphatidylserine. The current study was designed to investigate the incorporation of 22:6 omega 3 into outer segment phospholipids over 12 days and to determine whether the retina contained the enzymes necessary for elongation and desaturation of the major dietary precursor of 22:6 omega 3, the essential fatty acid linolenic acid (18:3 omega 3). Sprague-Dawley rats were injected intravitreally with [14C]22:6 omega 3 or [14C]18:3 omega 3 and kept in cyclic light (12 hr light/12 hr dark) for 2 hr to 12 days. Phospholipids from rod outer segments and the remaining retinal debris were separated by two-dimensional thin-layer chromatography. [14C]22:6 omega 3 radioactivity was initially highest in phosphatidylcholine and rapidly decreased from 45% of total phospholipid labeling at 2 hr to 26% by 1 and 3 days in ROS, while phosphatidylethanolamine labeling increased from 49 to 68% by 3 days and phosphatidylserine labeling increased from 3 to 14% over 12 days. Phenacyl derivatives of total fatty acids were separated by HPLC. A substantial conversion of [14C]18:3 to [14C]20:5, [14C]22:5 and [14C]22:6 was noted after 1 days, with increasing conversion to [14C]22:6 over the 12-day period. When only one eye was injected with [14C]18:3 omega 3, negligible radioactive fatty acids were detected in the contralateral eye from 1 to 12 days post-injection demonstrating that conversion of 18:3 to 22:6 occurred primarily within the injected eye. All enzymes for elongation and desaturation of 18:3 to 22:6 appear to be present in the eye. However, the conversion of 22:5 to 22:6 by delta-4 desaturase is evidently rate-limiting and may affect phospholipid replacement during photoreceptor outer segment renewal if this pathway proves to be essential for the supply of 22:6 during disk membrane formation.
Wetzel
M G
MG
Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, Bethesda, MD 20892.
Li
J
J
Alvarez
R A
RA
Anderson
R E
RE
O'Brien
P J
PJ
D000818:Animals; D002250:Carbon Radioisotopes / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000493:pharmacokinetics*; D008042:Linolenic Acids / Q000493:pharmacokinetics*; D008297:Male; D010713:Phosphatidylcholines / Q000096:biosynthesis; D010718:Phosphatidylserines / Q000096:biosynthesis; D010743:Phospholipids / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000201:enzymology / Q000378:metabolism*; D012374:Rod Cell Outer Segment / Q000378:metabolism*; D013997:Time Factors
D002250:Carbon Radioisotopes; D008042:Linolenic Acids; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D010743:Phospholipids; D004281:Docosahexaenoic Acids