Differences in the metabolism of eicosatetraenoic (20:4(n - 6)), tetracosatetraenoic (24:4(n - 6)) and triacontatetraenoic (30:4(n - 6)) acids in human neutrophils.
The metabolism of [1-14C]eicosatetraenoic (arachidonic, 20:4(n - 6)), [1-14C]tetracosatetraenoic (24:4(n - 6)) and [1-14C]triacontatetraenoic (30:4(n - 6)) acids was studied in intact human neutrophils. [1-14C]20:4(n - 6) and [1-14C]24:4(n - 6) were efficiently taken up by the neutrophils, esterified into neutral lipids and phospholipids, and elongated by up to four carbon units. In contrast, [1-14C]30:4(n - 6) was poorly incorporated into the cells and remained predominantly in the original unesterified form. The [1-14C]tetraenoic fatty acids were mainly esterified into triacylglycerol, suggesting that this lipid class is important in the intracellular trafficking of polyunsaturated fatty acids. The leukocytes demonstrated a low capacity to beta-oxidize and desaturate the fatty acid substrates. In the presence of calcium ionophore A23187 the neutrophils converted [1-14C]20:4(n - 6) to a variety of radiolabelled oxygenated fatty acid derivatives including prostaglandins, thromboxanes, mono- and dihydroxylated fatty acids and leukotrienes. The major eicosanoid products were 5-monohydroxy-20:4(n - 6) and leukotriene B4. In contrast, [1-14C]24:4(n - 6) was metabolized to radiolabelled monohydroxylated fatty acids (predominantly the 9-hydroxy positional isomer) but not to other lipoxygenase or cyclooxygenase products by the calcium ionophore-stimulated cells. Negligible oxygenated fatty acid compounds were formed from [1-14C]30:4(n - 6), indicating that it is a poor substrate for the neutrophil cyclooxygenase and lipoxygenase enzymes.
Robinson
B S
BS
Department of Chemical Pathology, Women's and Children's Hospital, North Adelaide, Australia.
Johnson
D W
DW
Ferrante
A
A
Poulos
A
A
D016718:Arachidonic Acid / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002250:Carbon Radioisotopes; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000096:biosynthesis*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010743:Phospholipids / Q000096:biosynthesis
D002250:Carbon Radioisotopes; D005231:Fatty Acids, Unsaturated; D008055:Lipids; D010743:Phospholipids; D016718:Arachidonic Acid; C065411:tetracosatetraenoic acid; D000001:Calcimycin; C088763:triacontatetraenoic acid