Metabolic conversion of C20 polymethylene-interrupted polyunsaturated fatty acids to essential fatty acids.

Polymethylene-interrupted (PMI)-polyunsaturated fatty acids (PUFA) are fatty acids present largely in gymnosperm. Sciadonic acid (SciA, 20:3 Δ-5,11,14) and juniperonic acid (JA, 20:4 Δ-5,11,14,17) are typical C20 PMI-PUFA with an isolated double bond at Δ5. Previously, we found that SciA and JA are converted to linoleic acid (LNA) and α-linolenic acid (ΑLA), respectively. The conversion process includes chain-shortening step by peroxisomal ß-oxidation for elimination a double bond at Δ5, and subsequent chain-elongation step in microsomes. In this study, we examined the substrate specificity of this metabolism in rodent and human cells. Supplementation of SciA, eicosadienoic acid (EDA, 20:2 Δ-11,14) or JA to CHO-K1 cells (wild type) induced an accumulation of LNA, LNA or ALA, respectively, in cellular lipids. These changes were not observed in the peroxisomes-deficient CHO cells, indicating involvement of peroxisomes in the metabolism. Two types of human cells (MKN74 and HepG2) also converted the C20 PMI-PUFA and EDA to the respective essential fatty acids. In contrast, no chain-shortened metabolite of pinolenic acid (18:3 Δ-5,9,12) was detected in any cell lines tested. From these results, C20 PMI-PUFA and EDA, but not C18 PMI-PUFA, are suggested as being effectively converted to essential fatty acids by the fatty acid remodeling system in rodent and human cells.

Metabolic pathway that produces essential fatty acids from polymethylene-interrupted polyunsaturated fatty acids in animal cells.

Sciadonic acid (20:3 Delta-5,11,14) and juniperonic acid (20:4 Delta-5,11,14,17) are polyunsaturated fatty acids (PUFAs) that lack the Delta-8 double bond of arachidonic acid (20:4 Delta-5,8,11,14) and eicosapentaenoic acid (20:5 Delta-5,8,11,14,17), respectively. Here, we demonstrate that these conifer oil-derived PUFAs are metabolized to essential fatty acids in animal cells. When Swiss 3T3 cells were cultured with sciadonic acid, linoleic acid (18:2 Delta-9,12) accumulated in the cells to an extent dependent on the concentration of sciadonic acid. At the same time, a small amount of 16:2 Delta-7,10 appeared in the cellular lipids. Both 16:2 Delta-7,10 and linoleic acid accumulated in sciadonic acid-supplemented CHO cells, but not in peroxisome-deficient CHO cells. We confirmed that 16:2 Delta-7,10 was effectively elongated to linoleic acid in rat liver microsomes. These results indicate that sciadonic acid was partially degraded to 16:2 Delta-7,10 by two cycles of beta-oxidation in peroxisomes, then elongated to linoleic acid in microsomes. Supplementation of Swiss 3T3 cells with juniperonic acid, an n-3 analogue of sciadonic acid, induced accumulation of alpha-linolenic acid (18:3 Delta-9,12,15) in cellular lipids, suggesting that juniperonic acid was metabolized in a similar manner to sciadonic acid. This PUFA remodeling is thought to be a process that converts unsuitable fatty acids into essential fatty acids required by animals.