Polyunsaturated thia- and oxa-fatty acids: incorporation into cell-lipids and their effects on arachidonic acid- and eicosanoid synthesis.
EPA, DHA, C15SCH2COOH (n-3), C15SCH2COOH (n-6) and C18SCH2COOH (n-3) are extensively incorporated into phospholipids and triacylglycerol in rat hepatocytes after 24 h incubation with 80 microM fatty acid/derivative. Only traces of polyunsaturated 3-oxa fatty acids (C15OCH2COOH, C18OCH2COOH) were incorporated. C15-S-butyric acid (n-3) is a stronger inhibitor of delta6-desaturase in rat liver-microsomes than C15SCH2COOH (n-3), C15-S-propionic acid (n-3), EPA and DHA. It inhibits delta5-desaturase in a similar manner to EPA and DHA. Arachidonic acid and C15SCH2COOH, (n-6) are better substrates for PGH-synthase than EPA and C15SCH2COOH, (n-3), showing the inhibitory effect of the n-3 bond. The n-3 polyunsaturated fatty acids, including the sulfur-substituted fatty acid derivatives, are poor substrates for PGH-synthase. However, they inactivate the PGH-synthase activity at least as efficiently as arachidonic acid. C15SCH2COOH (n-3), C15S(CH2)2COOH (n-3) and C18SCH2COOH (n-3) induce peroxisomal beta-oxidation more than EPA and DHA.
Larsen
L N
LN
Institute of Medical Biochemistry, University of Oslo, Norway.
Hørvik
K
K
Sørensen
H I
HI
Bremer
J
J
D042962:Acyl-CoA Oxidase; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000096:biosynthesis*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015777:Eicosanoids / Q000096:biosynthesis*; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D050356:Lipid Metabolism; D008114:Liver Neoplasms, Experimental; D017737:Macrophages, Peritoneal; D008297:Male; D051379:Mice; D008830:Microbodies / Q000201:enzymology; D010088:Oxidoreductases / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000378:metabolism; D014407:Tumor Cells, Cultured; D017965:gamma-Linolenic Acid / Q000096:biosynthesis
D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D005231:Fatty Acids, Unsaturated; D014280:Triglycerides; D016718:Arachidonic Acid; D017965:gamma-Linolenic Acid; D010088:Oxidoreductases; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D042962:Acyl-CoA Oxidase