Kobayashi J, Nishida T, Ameis D, Stahnke G, Schotz M C, Hashimoto H, Fukamachi I, Shirai K, Saito Y, Yoshida S
Second Department of Internal Medicine, School of Medicine, Chiba University, Japan.
Biochem Biophys Res Commun. 1992 Jan 15;182(1):70-7. doi: 10.1016/s0006-291x(05)80113-5.
Previously, we reported a case with type I hyperlipidemia due to a lipid interface recognition deficiency in lipoprotein lipase (LPL) (1). The LPL from postheparin plasma of this patient did not hydrolyze TritonX-100-triolein or very low density lipoprotein-triolein but did hydrolyze tributyrin and LysoPC-triolein substrates. Sequence analysis of the probands DNA revealed a heterozygous nucleotide change: a C----G transversion at position of 1595, resulting in changing the codon for Ser447 to a stop codon. Expression studies of this mutant LPLcDNA in Cos-1 cells produced and secreted considerable amounts of LPL mass in the culture media. The mutated LPL hydrolyzed much less TritonX-100-triolein than wild type LPL, whereas hydrolysis of tributyrin and LysoPC--triolein was the same with both the mutant and wild type LPL. These results suggest that this mutation might be responsible for the property of the LPL with a defect in lipid interface recognition in the type I patient we reported.
此前，我们报道过一例因脂蛋白脂肪酶（LPL）脂质界面识别缺陷导致的I型高脂血症病例（1）。该患者肝素后血浆中的LPL不能水解TritonX - 100 - 三油酸甘油酯或极低密度脂蛋白 - 三油酸甘油酯，但能水解三丁酸甘油酯和溶血磷脂酰胆碱 - 三油酸甘油酯底物。对先证者DNA的序列分析发现了一个杂合核苷酸变化：第1595位发生C→G颠换，导致Ser447密码子变为终止密码子。在Cos - 1细胞中对该突变型LPL cDNA进行表达研究，在培养基中产生并分泌了大量的LPL蛋白。与野生型LPL相比，突变型LPL水解TritonX - 100 - 三油酸甘油酯的能力大大降低，而突变型和野生型LPL对三丁酸甘油酯和溶血磷脂酰胆碱 - 三油酸甘油酯的水解能力相同。这些结果表明，我们报道的I型患者中LPL脂质界面识别缺陷的特性可能是由该突变所致。
