Rader D J, Schäfer J, Lohse P, Verges B, Kindt M, Zech L A, Steinmetz A, Brewer H B
Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Clin Invest. 1993 Aug;92(2):1009-17. doi: 10.1172/JCI116606.
Apolipoprotein (apo) A-IV is a polymorphic, intestinally derived apolipoprotein that is genetically linked to and similar in structure to apoA-I, the major apolipoprotein in high density lipoproteins (HDL). ApoA-IV plays a potentially important role in lipoprotein metabolism and reverse cholesterol transport, but its in vivo metabolism is poorly understood. In order to gain insight into factors modulating apoA-IV metabolism in humans, the in vivo kinetics of the two major human apoA-IV isoproteins apoA-IV-1 and apoA-IV-2 were investigated in normolipidemic human subjects. 131I-apoA-IV-1 and 125I-apoA-IV-2 were reassociated with autologous plasma and injected into study subjects. Analysis of the kinetic data revealed a rapid mean fractional catabolic rate (FCR) for apoA-IV-1 of 2.42 +/- 0.11 d-1. The mean production, or transport, rate of apoA-IV-1 was 16.3 +/- 1.4 mg/kg per d. Plasma apoA-IV concentrations were highly correlated with apoA-IV production rate (r = 0.84, P < 0.001) and not correlated with apoA-IV fractional catabolic rate (r = 0.25, P = NS). The mean FCR of apoA-IV-2 was 2.21 +/- 0.10 d-1. In the ten subjects in whom 131I-apoA-IV-1 and 125I-apoA-IV-2 were simultaneously injected, the FCR of apoA-IV-2 was significantly slower by paired t test (P = 0.003). The FCR of apoA-IV-2 in an apoA-IV-2/2 homozygote was only 1.49 d-1, substantially slower than in all other subjects. We conclude that: (a) apoA-IV is a rapidly catabolized apolipoprotein in humans, with a fractional catabolic rate more than 10 times greater than that of apoA-I; (b) apoA-IV has a high absolute transport rate similar to that of apoA-I; (c) plasma levels of apoA-IV are primarily determined by apoA-IV production rate in normolipidemic subjects; and (d) the fractional catabolic rate of the common variant apoA-IV-2 is slower than that of the wild-type apoA-IV-1.
载脂蛋白（apo）A-IV是一种多态性的、源自肠道的载脂蛋白，在基因上与高密度脂蛋白（HDL）中的主要载脂蛋白apoA-I相关联且结构相似。apoA-IV在脂蛋白代谢和逆向胆固醇转运中发挥着潜在的重要作用，但其体内代谢情况却知之甚少。为了深入了解调节人类apoA-IV代谢的因素，我们在血脂正常的人类受试者中研究了两种主要的人类apoA-IV同工型apoA-IV-1和apoA-IV-2的体内动力学。将131I-apoA-IV-1和125I-apoA-IV-2与自体血浆重新结合后注入研究对象体内。对动力学数据的分析显示，apoA-IV-1的平均分数分解代谢率（FCR）很快，为2.42±0.11 d-1。apoA-IV-1的平均产生率或转运率为16.3±1.4 mg/kg per d。血浆apoA-IV浓度与apoA-IV产生率高度相关（r = 0.84，P < 0.001），与apoA-IV分数分解代谢率无相关性（r = 0.25，P =无显著性差异）。apoA-IV-2的平均FCR为2.21±0.10 d-1。在同时注射131I-apoA-IV-1和125I-apoA-IV-2的10名受试者中，通过配对t检验，apoA-IV-2的FCR明显较慢（P = 0.003）。apoA-IV-2/2纯合子中apoA-IV-2的FCR仅为1.49 d-1，明显慢于所有其他受试者。我们得出以下结论：（a）apoA-IV在人类中是一种快速分解代谢的载脂蛋白，其分数分解代谢率比apoA-I高10倍以上；（b）apoA-IV具有与apoA-I相似的高绝对转运率；（c）在血脂正常的受试者中，血浆apoA-IV水平主要由apoA-IV产生率决定；（d）常见变异型apoA-IV-2的分数分解代谢率比野生型apoA-IV-1慢。
