METABOLISM OF APOA-IV IN HUMANS

载脂蛋白（apo）A-IV与富含磷脂酰肌醇的 脂蛋白（TRL）和高密度脂蛋白（HDL）。 虽然它的 确切的作用知之甚少，有人建议参与 甘油三酯代谢以及胆固醇逆向转运。 ApoA-IV是一种多态性蛋白， 主要的同种型已被鉴定。 apoA-IV-2同工蛋白已被 与低甘油三酯和高密度脂蛋白水平比大多数 常见的apoA-IV-I同种蛋白。 这两种形式都进行了动力学研究， 几个受试者，包括6个apoA-IV-1/2杂合子和1个 apoA-IV-2/2纯合子。 apoA-IV-2形式具有显著的 比apoA-IV-l形式的分解代谢速率慢，并且在纯合子中， 明显变慢。 apoA-IV-2/2纯合子中的ApoA-I代谢为 正常 这为高密度脂蛋白的机制提供了新的见解 与apoA-IV-2相关的水平。 已发现ApoA-IV血浆水平与 与血浆甘油三酯水平呈负相关，而apoA-I水平与血浆甘油三酯水平呈负相关。 相关的 确定了这种关联的代谢解释 通过研究apoA-IV和apoA-I在患有糖尿病的受试者中的代谢， 与正常受试者相比。 两 外源标记的放射性示踪剂和内源标记的稳定的 使用了同位素。 在高血糖症患者中， apoA-IV的分解速率较正常人明显延迟， 尽管apoA-1催化速率增加。 因此，我们认为， 高脂血症对apoA-IV和apoA-I具有相反的作用 尽管这些载脂蛋白在 等离子体 高水平的apoA-IV水平与高水平的 甘油三酯是由于apoA-IV催化速率的延迟， 而不是增加这种载脂蛋白的合成速率。 这些研究包括20至55岁的受试者。 四十 在这些研究中，有10%的受试者是女性。 研究 包括一名非洲裔美国人，一名西班牙裔和两名亚洲受试者。

Apolipoprotein (apo) A-IV is associated with both triglyceride-rich lipoproteins (TRL) and high density lipoproteins (HDL). Though its precise role is poorly understood, it has been proposed to be involved in both triglyceride metabolism as well as reverse cholesterol transport. ApoA-IV is a polymorphic protein, and the molecular basis for all four major isoforms has been identified. The apoA-IV-2 isoprotein has been associated with lower triglyceride and higher HDL levels than the most common apoA-IV-l isoprotein. Both forms have been studied kinetically in several subjects, including six heterozygotes for apoA-IV-1/2 and one homozygote for apoA-IV-2/2. The apoA-IV-2 form has a significantly slower catabolic rate than the apoA-IV-l form, and in the homozygote was markedly slower. ApoA-l metabolism in the apoA-IV-2/2 homozygote was normal. This provides new insight into the mechanism of the higher HDL levels associated with apoA-IV-2. ApoA-IV plasma levels have been found to be positively associated with plasma triglyceride levels, whereas levels of apoA-l are inversely correlated. The metabolic explanation of this association was determined by studying the metabolism of apoA-IV and apoA-l in subjects with hypertriglyceridemia compared with normal subjects. Both exogenously-labeled radiotracers and endogenous labeling with stable isotopes were utilized. In the hypertriglyceridemic patients, the catabolic rate of apoA-IV was markedly delayed compared with normal, despite an increase in the rate of apoA-l catabolism. Hence, hypertriglyceridemia has opposite effects on apoA-IV and apoA-l catabolism, despite the close association of these apolipoproteins in plasma. The higher apoA-IV levels seen with higher levels of triglycerides are due to a delay in the rate of apoA-IV catabolism, rather than an increased synthetic rate of this apolipoprotein. These studies included subjects of age 20 to 55 years. Forty percent of the subjects in these studies were women. The studies included one African-American, one Hispanic, and two Asian subjects.