Reevaluation of the pathway for the metabolism of 7,10,13, 16-docosatetraenoic acid to 4,7,10,13,16-docosapentaenoic acid in rat liver.
When rat liver microsomes were incubated with [1-14C]22:4(n-6) under standard conditions for measuring acyl-CoA desaturases, it was not possible to detect the synthesis of any 22:5(n-6). When malonyl-CoA and NADPH were included in the incubation, 22:4(n-6) was chain elongated to 24:4(n-6), which was then desaturated to 24:5(n-6). Rat hepatocytes metabolized [1-14C]22:4(n-6), [3-14C]24:4(n-6), and [3-14C]24:5(n-6) to yield esterified radioactive 22:5(n-6). The results show that 22:4(n-6) is the precursor of 22:5(n-6) but the pathway is independent of an acyl-CoA-dependent 4-desaturase and probably requires intracellular communication between the endoplasmic reticulum and a site for beta-oxidation. Microsomal reaction rates for (n-6) versus (n-3) polyunsaturated fatty acid biosynthesis cannot per se be used to explain why in vivo most membrane lipids preferentially accumulate 22:6(n-3) rather than 22:5(n-6). Rates of desaturation of 24:4(n-6) and 24:5(n-3) at position 6 were similar (M. Geiger et al., Biochim. Biophys. Acta 1170, 137-142, 1993). We now show that 20:4(n-6) and 20:5(n-3) are chain elongated at the same rate as are 22:4(n-6) and 22:5(n-3). At present, no single reaction can be defined as being substrate specific or rate limiting to explain why there is an apparent selective synthesis and acylation of 22:6(n-3) rather than 22:5(n-6) into membrane lipids.
Mohammed
B S
BS
Department of Medical Biochemistry, Ohio State University, Columbus 43210.
Sankarappa
S
S
Geiger
M
M
Sprecher
H
H
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004883:Erucic Acids / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013379:Substrate Specificity
D004883:Erucic Acids; D005231:Fatty Acids, Unsaturated; C011395:adrenic acid; C026219:docosapentaenoic acid