Almeida Katia A, Schreiber Roberto, Amâncio Rosângela F, Bydlowski Sérgio P, Debes-Bravo Adriana, Issa Jacqueline S, Strunz Célia M C, Maranhão Raul C
Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Clin Chim Acta. 2003 Sep;335(1-2):157-63. doi: 10.1016/s0009-8981(03)00289-4.
Lipoprotein lipase catalyzes the hydrolysis of the triglycerides contained in both very-low-density lipoproteins and chylomicrons for storage in the adipose tissue and muscle of fats of both hepatic and dietary origin. The S447X-Stop lipoprotein lipase is the most common polymorphism of the enzyme, affecting roughly 20% of the population and is accompanied by normal or diminished fasting triglycerides and perhaps lower incidence of coronary artery disease (CAD). Delay in the removal of chylomicron and remnant is now an established risk factor for CAD.
Currently, the chylomicron metabolism has been evaluated in 12 normolipidemic subjects with the S447X-Stop and in 13 age- and sex-paired control subjects with no mutation. The doubly labeled chylomicron-like emulsion method was used to evaluate chylomicron metabolism. The emulsions labeled with cholesteryl-oleate (14C-CE) and tri[9,10-3H]oleate (3H-Tg) were injected intravenously and the decay curves of the labels were determined by blood sampling over 60 min followed by radioactive counting.
The fractional clearance rate (FCR, min(-1)) of the labels was not different in the S447X carriers compared with the noncarriers (FCR 3H-Tg 0.035 +/- 0.019 and 0.030 +/- 0.009; FCR 14C-CE 0.008 +/- 0.007 and 0.009 +/- 0.007, respectively).
The chylomicron intravascular lipolysis monitored by the 3H-Tg emulsion and the remnant removal monitored by the 14C-CE emulsion were not altered by the presence of this polymorphism of great populational impact.
脂蛋白脂肪酶催化极低密度脂蛋白和乳糜微粒中所含甘油三酯的水解,以便将源自肝脏和饮食的脂肪储存于脂肪组织和肌肉中。S447X - Stop脂蛋白脂肪酶是该酶最常见的多态性,影响约20%的人群,伴有空腹甘油三酯正常或降低,且冠心病(CAD)发病率可能较低。乳糜微粒和残余颗粒清除延迟现已被确认为CAD的一个危险因素。
目前,已对12名携带S447X - Stop的血脂正常受试者和13名无突变的年龄及性别匹配的对照受试者的乳糜微粒代谢进行了评估。采用双标记乳糜微粒样乳剂法评估乳糜微粒代谢。将用胆固醇油酸酯(14C - CE)和三[9,10 - 3H]油酸酯(3H - Tg)标记的乳剂静脉注射,通过在60分钟内采血并进行放射性计数来测定标记物的衰变曲线。
与非携带者相比,S447X携带者中标记物的分数清除率(FCR,min(-1))无差异(3H - Tg的FCR分别为0.035±0.019和0.030±0.009;14C - CE的FCR分别为0.008±0.007和0.009±0.007)。
由3H - Tg乳剂监测的乳糜微粒血管内脂解和由14C - CE乳剂监测的残余颗粒清除,并未因这种具有重大人群影响的多态性的存在而改变。