Complete deficiency of erythrocyte type isozyme of AMP deaminase in human

人体内存在多种组织特异性AMP脱氨酶同工酶。它们是红细胞型（< e_1>, < e_2>），肝脏型(L)和肌肉型(M)。同工酶M缺乏症是由Fishbein等人于1978年报道的。我们发现6例红细胞AMP脱氨酶完全缺乏症。他们都很健康，没有血液病。与对照组相比，血清尿酸水平略低。为了排除红细胞糖酵解缺陷，测定了缺陷个体红细胞中2,3-二磷酸甘油酸（DPG）和ATP的含量。DPG含量与对照组无明显差异。AMP脱氨酶缺陷细胞中ATP水平明显升高；缺陷细胞的水平平均高出50%。代谢研究表明，缺陷细胞中腺嘌呤核苷酸的降解速度较慢，这些缺陷细胞在维持腺嘌呤核苷酸库方面更有效。红细胞型同工酶缺陷较多；具有同工酶L的单核细胞和血小板显示正常水平的AMP脱氨酶活性。在已知的AMP脱氨酶同工酶中，<E_2>在动力学和免疫学性质上与<E_1>非常相似。红细胞AMP脱氨酶完全缺乏的受试者均缺乏<E_1>和<E_2>。这些结果表明这两种同工酶是同一基因的产物。为了进一步研究这种酶缺乏症的分子机制，我们利用缺酶个体建立了EB病毒转化的b淋巴母细胞系。正常细胞系表达红细胞型同工酶，而来自缺陷个体的细胞系不表达红细胞型同工酶。从熟悉的研究来看，很明显该缺陷是作为常染色体隐性性状遗传的。突变基因的频率高得惊人，在日本、首尔和台北，大约30个人群中有一个杂合子，导致大约3600个人群中有一个完全缺失。然而，根据个人通讯，在比利时和以色列没有发现杂合子。因此，这种缺陷可能只在东方人中常见。少

There are multiple tissue specific AMP deaminase isozymes in human. They are erythrocyte type ( <E_1> , <E_2> ), liver type (L) and muscle type (M). The deficiency of isozyme M was reported in 1978 by Fishbein et al.We have found six individuals with complete deficiency of erythrocyte AMP deaminase. They are all healthy and have no hematological disorders. Serum uric acid levels were slightly lower comparing to the control. In order to exclude an erythrocyte glycolysis defect, 2,3-diphosphoglycerate (DPG) and ATP contents of the erythrocyte from the deficient individuals were determined. There was no distinct difference in DPG content from the control value. ATP levels were apparently higher in the AMP deaminase deficient cells; on average, the level is 50 % higher in the deficient cells. Metabolic studies indicated the slower degradation of adenine nucleotide in deficient cells and these deficient cells are rather more efficient in maintaining the adenine nucleotide pool. The deficien … More cy is only in erythrocyte type isozyme; monomuclear cells and platelets, which have isozyme L, show normal level of AMP deaminase activity. Of the known AMP deaminase isozymes, <E_2> is very similar to <E_1> in kinetic and immnological properties. The subjects with complete deficiency of erythrocyte AMP deaminase lack both <E_1> and <E_2> . These results indicate that these two isozymes are the product of the same gene. To study on the molecular mechanism of this enzyme deficiency in future, EB virus transformed B-lymphoblast cell lines were established from the deficient individuals. Normal cell lines express erythrocyte type isozyme, but the cell lines derived from the deficient individuals do not express erythrocyte type isozyme. From the familiar study, it is evident the deficiency is inherited as an autosomal recessive trait. The frequency of the mutant gene is surprisingly high, one heterozygote in about 30 of the population in Japan, Seoul and Taipei, resulting in one complete deficiency in about 3,600 population. However, according to the personal communications no heterozygote was found in Belgium and Israel. Therfore, this deficiency may be only common in oriental people. Less