An inherited molecular lesion of erythrocyte pyruvate kinase. Identification of a kinetically aberrant isozyme associated with premature hemolysis.
An inherited molecular lesion of erythrocyte pyruvate kinase. Identification of a kinetically aberrant isozyme associated with premature hemolysis.
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红细胞丙酮酸激酶的遗传性分子损伤。
DOI：
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发表时间：
1968
影响因子：
15.9
通讯作者：
Ross McINTymE
中科院分区：
文献类型：
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作者：
D. Paglia;William N. VALENIrNE;M. Baughan;DENs R. Meilr;C. Reed;Ross McINTymE
已注意到遗传性溶血性贫血的非典型病例，其临床和生化符合红细胞激酶（PK）缺陷型贫血，但通过常规测定程序发现存在明显足量的红细胞PK活性。四个这样的异常情况下，发生在两个无关的家庭，调查。红细胞含有丙酮酸激酶（PK（2））的动力学异常同工酶。米氏常数的病理同工酶相对于磷酸烯醇丙酮酸超过10倍以上的控制值，但没有动力学异常是明显的第二基板，腺苷二磷酸。PK（2）的最适pH值比野生型酶（PK（1））低近1U。同工酶的功能稳定性也存在显著差异。白细胞未受影响。家族研究揭示了通常类型的定量PK缺乏的父系杂合性。临床正常的母系亲属和一些兄弟姐妹表现出红细胞PK动力学和反应特征的中间偏差，与正常PK（1）和动力学异常PK（2）共存一致。先证者的溶血性贫血似乎需要同时遗传控制PK（2）产生的基因及其推测的等位基因，从而导致定量PK缺乏。这两种遗传缺陷都追溯到三代，两种情况下的缺陷基因显然都存在于常染色体上。建议对PK测定技术进行修订，因为PK（2）的催化无效性仅在低底物浓度下表现出来，因此在常规测定中使用的相对较高的磷酸烯醇丙酮酸水平下无法检测到。
Atypical cases of heritable hemolytic anemia have been noted that conform clinically and biochemically to anemias of the pyruvatekinase (PK)-deficient type, except for the presence of apparently adequate quantities of erythrocyte-PK activity by the usual assay procedure. Investigations of four such anomalous cases, occurring in two unrelated families, are presented. Erythrocytes contained a kinetically aberrant isozyme of pyruvate kinase (PK(2)). Michaelis constants for the pathologic isozyme relative to phosphoenolpyruvate were over 10-fold greater than control values, but no kinetic abnormality was evident for the second substrate, adenosine diphosphate. PK(2) exhibited a pH optimum almost 1 U lower than the wild enzyme form (PK(1)). Significant differences were also evident in the functional stabilities of the isozymes. Leukocytes were unaffected. Family studies revealed paternal heterozygosity for quantitative PK deficiency of the usual type. Clinically normal maternal relatives and some siblings demonstrated intermediate deviations in erythrocyte-PK kinetics and reaction characteristics compatible with coexistence of normal PK(1) and kinetically abnormal PK(2). Hemolytic anemia in the propositi appeared to require simultaneous inheritance of the gene governing PK(2) production and its presumed allele resulting in quantitative PK deficiency. Both genetic defects were traced through three generations, the defective gene in both instances apparently resident on autosomes.A revision of the PK assay technique is suggested, since catalytic inefficiency of PK(2) was manifested only at low substrate concentrations and was therefore undetectable at the relatively high phosphoenolpyruvate levels employed in the conventional assay.