IN VIVO LABILITY OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE IN GDA- AND GDMEDITERRANEAN DEFICIENCY
IN VIVO LABILITY OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE IN GDA- AND GDMEDITERRANEAN DEFICIENCY
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DOI：
10.1172/jci105786
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发表时间：
1968-01-01
影响因子：
15.9
通讯作者：
AMOROSI, EL
中科院分区：
文献类型：
--
作者：
PIOMELLI, S;CORASH, LM;AMOROSI, EL
G6 PD水平的降低可能是由于合成速率降低、催化效率较低的酶的合成、不稳定性增加或组合机制所致。为了检验不稳定性增加的假设，通过含有平均年龄逐渐增加的红细胞的组分中活性下降的斜率，测量了3组个体（对照组、Gd（[长划线]），A-雄性和Gd（[长划线]），地中海雄性）体内酶的下降速率。这些组分通过在不含污染血小板和白细胞的红细胞悬浮液的不连续密度梯度上超离心获得。还测量了丙酮酸激酶（另一种年龄依赖性酶）的体内下降速率，发现3组非常相似。G6 PD的体内下降遵循指数速率，对照的半衰期为62天，GD（[长破折号]），A-红细胞的半衰期为13天。正常网织红细胞中的活性估计为9.7 U，Gd（[长破折号]）、A（长破折号]网织红细胞中的活性估计为8.8 U。这些估计值通过直接测量从极度网织红细胞增多症患者中分离的网织红细胞得到证实。在Gd（-）中，仅在网织红细胞中显示地中海红细胞活性，估计平均为1.4 U。下降速度非常快，以至于在成熟红细胞中检测不到活性。这些数据表明，G6 PD缺乏的GdA-和Gd地中海变体的结果从不同程度的体内不稳定的异常酶。
A decreased level of G6PD might result from decreased rate of synthesis, synthesis of an enzyme of lower catalytic efficiency, increased lability, or a combined mechanism. To test the hypothesis of increased lability, the rate of decline of the enzyme in vivo was measured in 3 groups of individuals, controls, Gd([long dash]),A-males, and Gd([long dash]), Mediterranean males, by the slope of decline of activity in fractions containing eryth-ocytes of progressively increasing mean age. These fractions were obtained by ultracentrifugation on a discontinuous density gradient of erythrocyte suspensions free of contaminating platelets and leukocytes. The rate of in vivo decline of pyruvate kinase (another age de pendent enzyme) was also measured and found very similar in the 3 groups. The in vivo decline of G6PD followed an exponential rate, with a half-life of 62 days for controls and 13 days for GD([long dash]),A- erythro-cytes. The activity in normal reticulocytes was estimated at 9.7 U and in Gd([long dash]),A[long dash]reticulocytes at 8.8 U. These estimates were confirmed by direct measurements in reticulocytes isolatedfrompatients with extreme reticulocytosis. In Gd(-),Mediterranean erythrocytes activity could be demonstrated only in reticulocytes, which were estimated to average 1.4 U. The rate of decline is so extreme that no activity could be detected in mature erythrocytes. These data suggest that the G6PD deficiency of both the GdA- and the GdMediterranean variant results from different degrees of in vivo instability of the abnormal enzyme.