Regulation of the biosynthesis of 4,7,10,13,16-docosapentaenoic acid

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Date
1997-09-01Author
Mohammed, B. Selma
Luthria, Devanand L.
Bakousheva, Svetla P.
Sprecher, Howard
Citation
B. S. Mohammed, B. S., D. L. Luthria, S. P. Baykousheva, and H. Sprecher, “Regulation of the biosynthesis of 4,7,10,13,16-docosapentaenoic acid,” Biochemical Journal 326 (1997): 425-430.
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Show full item recordAbstract
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 C#% fatty
acid was esteri®ed to 1-acyl-sn-glycero-3-phosphocholine (1-acyl-
GPC) by microsomes, whereas the rates of esteri®cation 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-"%C]-
9,12,15,18-24:4 compared with 6,9,12,15,18-24:5. Only
[1-"%C]7,10,13,16-22:4 accumulated when [3-"%C]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-"%C]6,9,12,15,18-24:5.
When the two C#% fatty acids were incubated with peroxisomes,
microsomes and 1-acyl-GPC there was a decrease in the production
of acid-soluble radioactivity from [3-"%C]6,9,12,15,18-24:5, but not from [3-"%C]9,12,15,18-24:4. The preferential fate
of [1-"%C]4,7,10,13,16-22:5, when it was produced, was to move
out of peroxisomes for esteri®cation into the acceptor, whereas
only small amounts of 7,10,13,16-22:4 were esteri®ed. By using
#H-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 esteri®ed arachidonate. Collectively, the results show
that an inverse relationship exists between rates of peroxisomal
b-oxidation and of esteri®cation into 1-acyl-GPC by microsomes.
Most importantly, when a fatty acid is produced with its ®rst
double bond at position 4, it preferentially moves out of
peroxisomes for esteri®cation to 1-acyl-GPC by microsomes,
rather than being degraded further via a cycle of b-oxidation that
requires NADPH-dependent 2,4-dienoyl-CoA reductase.