Regulation of the biosynthesis of 4,7,10,13,16-docosapentaenoic acid.
It is now established that fatty acid 7,10,13,16-22:4 is metabolized into 4,7,10,13,16-22:5 as follows: 7,10,13,16-22:4-->9,12,15, 18-24:4-->6,9,12,15,18-24:5-->4,7,10,13,16-22:5. Neither C24 fatty acid was esterified to 1-acyl-sn-glycero-3-phosphocholine (1-acyl-GPC) by microsomes, whereas the rates of esterification of 4, 7,10,13,16-22:5, 7,10,13,16-22:4 and 5,8,11,14-20:4 were respectively 135, 18 and 160 nmol/min per mg of microsomal protein. About four times as much acid-soluble radioactivity was produced when peroxisomes were incubated with [3-14C]9,12,15,18-24:4 compared with 6,9,12,15,18-24:5. Only [1-14C]7,10,13,16-22:4 accumulated when [3-14C]9,12,15,18-24:4 was the substrate, but both 4,7,10,13,16-22:5 and 2-trans-4,7,10,13,16-22:6 were produced from [3-14C]6,9,12,15, 18-24:5. When the two C24 fatty acids were incubated with peroxisomes, microsomes and 1-acyl-GPC there was a decrease in the production of acid-soluble radioactivity from [3-14C]6,9,12,15, 18-24:5, but not from [3-14C]9,12,15,18-24:4. The preferential fate of [1-14C]4,7,10,13,16-22:5, when it was produced, was to move out of peroxisomes for esterification into the acceptor, whereas only small amounts of 7,10,13,16-22:4 were esterified. By using 2H-labelled 9,12,15,18-24:4 it was shown that, when 7,10,13,16-22:4 was produced, its primary metabolic fate was degradation to yield esterified arachidonate. Collectively, the results show that an inverse relationship exists between rates of peroxisomal beta-oxidation and of esterification into 1-acyl-GPC by microsomes. Most importantly, when a fatty acid is produced with its first double bond at position 4, it preferentially moves out of peroxisomes for esterification to 1-acyl-GPC by microsomes, rather than being degraded further via a cycle of beta-oxidation that requires NADPH-dependent 2,4-dienoyl-CoA reductase.
Mohammed
B S
BS
Department of Medical Biochemistry, The Ohio State University, Columbus 43210, USA.
Luthria
D L
DL
Bakousheva
S P
SP
Sprecher
H
H
D000215:Acylation; D000818:Animals; D001667:Binding, Competitive; D004951:Esterification; D005227:Fatty Acids / Q000378:metabolism; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis* / Q000378:metabolism; D005232:Fatty Acids, Volatile / Q000378:metabolism; D008297:Male; D008830:Microbodies / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D010767:Phosphorylcholine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D005232:Fatty Acids, Volatile; D010767:Phosphorylcholine; C026219:docosapentaenoic acid