Robinson B S, Johnson D W, Ferrante A, Poulos A
Department of Chemical Pathology, Women's and Children's Hospital, North Adelaide, Australia.
Biochim Biophys Acta. 1994 Aug 4;1213(3):325-34. doi: 10.1016/0005-2760(94)00059-x.
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.
在完整的人中性粒细胞中研究了[1-¹⁴C]二十碳四烯酸（花生四烯酸，20:4(n - 6)）、[1-¹⁴C]二十四碳四烯酸（24:4(n - 6)）和[1-¹⁴C]三十碳四烯酸（30:4(n - 6)）的代谢情况。[1-¹⁴C]20:4(n - 6)和[1-¹⁴C]24:4(n - 6)被中性粒细胞有效摄取，酯化到中性脂质和磷脂中，并延长多达四个碳单位。相比之下，[1-¹⁴C]30:4(n - 6)很少掺入细胞中，主要以原始的未酯化形式存在。[1-¹⁴C]四烯酸脂肪酸主要酯化到三酰甘油中，表明该脂质类别在多不饱和脂肪酸的细胞内运输中很重要。白细胞对脂肪酸底物进行β氧化和去饱和的能力较低。在钙离子载体A23187存在的情况下，中性粒细胞将[1-¹⁴C]20:4(n - 6)转化为多种放射性标记的氧化脂肪酸衍生物，包括前列腺素、血栓素、单羟基和二羟基脂肪酸以及白三烯。主要的类二十烷酸产物是5-单羟基-20:4(n - 6)和白三烯B4。相比之下，[1-¹⁴C]24:4(n - 6)被钙离子载体刺激的细胞代谢为放射性标记的单羟基脂肪酸（主要是9-羟基位置异构体），但未代谢为其他脂氧合酶或环氧化酶产物。由[1-¹⁴C]30:4(n - 6)形成的氧化脂肪酸化合物可忽略不计，表明它是中性粒细胞环氧化酶和脂氧合酶的不良底物。
