Hagve T A, Christensen E, Grønn M, Christophersen B O
Institute of Clinical Biochemistry, University of Oslo, Rikshospitalet, Norway.
Scand J Clin Lab Invest Suppl. 1988;191:33-46.
The object of the present work has been to assess some aspects of the control of the metabolism of polyunsaturated fatty acids. In these studies we have used isolated cells; hepatocytes and cardiac myocytes from rat, and lymphocytes and fibroblasts from humans. Attention has focused on the importance of dietary and hormonal factors which can exert an effect shortly after activation of fatty acid, and thus may determine whether the fatty acid will be desaturated, chain-elongated, directly esterified or oxidized. Both the short-term and long-term regulation excerted by dietary fat have been studied in both rat and human. Profound sex-differences exist in fatty acid esterification, oxidation and fatty acid composition in lipoproteins. It is suggested that these differences, at least in part are due to a different content of intracellular fatty acid binding proteins in female and male liver. The peroxisomal retroconversion of C22-unsaturated fatty acids to their C20-homologues is probably involved in the regulation of fatty acid composition in membrane phospholipids, being a sort of "overflow valve". In several somewhat different diseases the patients have no peroxisomes or their peroxisomes are defective. In these peroxisomal diseases the beta-oxidation of very long-chain fatty acids is deficient. In this present work we show that fibroblast from patients with the peroxisomal diseases, Zellweger disease, X-linked adrenoleukodystrophy and neonatal adrenoleukodystrophy differ in their ability to shorten C22-fatty acids.
本研究的目的是评估多不饱和脂肪酸代谢调控的某些方面。在这些研究中，我们使用了分离的细胞；大鼠的肝细胞和心肌细胞，以及人类的淋巴细胞和成纤维细胞。注意力集中在饮食和激素因素的重要性上，这些因素在脂肪酸激活后不久就能发挥作用，从而可能决定脂肪酸是否会去饱和、链延长、直接酯化或氧化。在大鼠和人类中都研究了膳食脂肪所施加的短期和长期调节。在脂肪酸酯化、氧化以及脂蛋白中的脂肪酸组成方面存在显著的性别差异。有人认为，这些差异至少部分是由于雌性和雄性肝脏中细胞内脂肪酸结合蛋白的含量不同所致。C22不饱和脂肪酸向其C20同系物的过氧化物酶体逆向转化可能参与了膜磷脂中脂肪酸组成的调节，是一种“溢流阀”。在几种略有不同的疾病中，患者没有过氧化物酶体或其过氧化物酶体有缺陷。在这些过氧化物酶体疾病中，极长链脂肪酸的β氧化不足。在本研究中，我们表明，患有过氧化物酶体疾病、脑肝肾综合征、X连锁肾上腺脑白质营养不良和新生儿肾上腺脑白质营养不良的患者的成纤维细胞在缩短C22脂肪酸的能力上存在差异。
