Alternate pathways in the desaturation and chain elongation of linolenic acid, 18:3(n-3), in cultured glioma cells.
Cultured C6 glioma cells rapidly incorporate and metabolize the essential fatty acids, 18:2(n-6) and 18:3(n-3), to 20- and 22-carbon polyunsaturated fatty acids. Using several deuterated fatty acid substrates we have obtained data that suggest alternate pathways, one possibly involving delta 8-desaturation, may exist in glioma cells for formation of 20:5(n-3) and 22:6(n-3) from 18:3(n-3). With 18:3(n-3)-6,6,7,7-d4 practically no 18:4(n-3)-6,7-d2 or 20:4(n-3)-8,9-d2 was detected whereas 20:3(n-3)-8,8,9,9-d4 accounted for 3.4% and delta 5,11,14,17-20:4-8,8,9,9-d4 for 21.1% of the total deuterated fatty acids recovered in phospholipids after a 16 h incubation; 20:5(n-3)-8,9-d2, 22:5(n-3)-10,11-d2, and 22:6(n-3)-10,11-d2 accounted for 42.4%, 13.2%, and 2.8% of deuterated acyl chains, respectively. When added exogneously, 20:3-8,8,9,9,-d4 was extensively converted to delta 5,11,14,17-20:4(n-3)-8,8,9,9-d4 (45%) and 20:5(n-3)-8,9-d2 (24%); a small amount (4%) of 18:3(n-3)-d4 also was detected. Both 20:4(n-3)-8,9-d2 and 18:4(n-3)-12,13,15,16-d4 were also converted to 20:5(n-3) and 22:6(n-3) with 8 and 0% of the respective original deuterated substrate remaining after 16 h. A possible pathway for 18:3(n-3) metabolism in glioma cells is described whereby an initial chain elongation step is followed by successive delta 5 and delta 8 desaturation reactions resulting in 20:5(n-3) formation and accounting for the ordered removal of deuterium atoms. Alternatively, extremely effective retroconversion may occur to chain shorten 20:3(n-3)-d4 to 18:3(n-3)-d4 followed by rapid conversion through the classical desaturation and chain elongation sequence.(ABSTRACT TRUNCATED AT 250 WORDS)
Cook
H W
HW
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
Byers
D M
DM
Palmer
F B
FB
Spence
M W
MW
Rakoff
H
H
Duval
S M
SM
Emken
E A
EA
D000818:Animals; D002849:Chromatography, Gas; D003903:Deuterium; D005227:Fatty Acids / Q000032:analysis; D005228:Fatty Acids, Essential / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis*; D005910:Glioma / Q000378:metabolism*; D008042:Linolenic Acids / Q000378:metabolism*; D013058:Mass Spectrometry; D008954:Models, Biological; D051381:Rats; D014407:Tumor Cells, Cultured
D005227:Fatty Acids; D005228:Fatty Acids, Essential; D005231:Fatty Acids, Unsaturated; D008042:Linolenic Acids; D003903:Deuterium