Complete deficiency of erythrocyte type isozyme of AMP deaminase in human

人红细胞型AMP脱氨酶同工酶完全缺乏

• 批准号: 60571084
• 负责人: OGASAWARA Nobuaki
• 金额: $ 1.09万
• 依托单位: Institute for Developmental Research, Aichi Prefectural Colony
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60571084/
• 关键词: Deficiency; Erythrocyte; AMP deaminase; Human; 完全欠損; 酵素欠損; プリン代謝

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

人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>），肝型（L）和肌肉型（M）。1978年Fishbein等报道了红细胞AMP脱氨酶同工酶M缺乏症。他们都很健康，没有血液系统疾病。血清尿酸水平略低于对照组。为了排除红细胞糖酵解缺陷，测定了缺陷个体红细胞的2，3-二磷酸甘油酸（DPG）和ATP含量。DPG含量与对照值无明显差异。AMP脱氨酶缺陷细胞中的ATP水平明显更高;平均而言，缺陷细胞中的水平高50%。代谢研究表明，腺嘌呤核苷酸在缺陷细胞中降解较慢，这些缺陷细胞在维持腺嘌呤核苷酸库方面更有效。缺陷 ...更多信息 半胱氨酸只存在于红细胞型同工酶中，而单核细胞和血小板具有同工酶L，AMP脱氨酶活性正常。在已知的AMP脱氨酶同工酶中，<E_2>它在<E_1>动力学和免疫学性质上与之非常相似。红细胞AMP脱氨酶完全缺乏者，两者均<E_1>缺乏<E_2>。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的分子机制，从缺乏的个体建立了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，但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，很明显，缺乏是作为一个常染色体隐性遗传性状。突变基因的频率惊人地高，在日本、首尔和台北，约30个人口中有一个杂合子，导致约3,600个人口中有一个完全缺乏。然而，根据个人来文，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

项目成果

N. Ogasawara: Plenum, Purine and pyrimidine metabolism in man V (ed. W.L.Nyhan et al.). Deficiency of erythrocyte type isozyme of AMP deaminase in human, 123-127 (1986)

N. Ogasawara：Man V 中的静压、嘌呤和嘧啶代谢（W.L.Nyhan 等编辑）。

小笠原信明: Human Genetics. 75. 15-18 (1987)

小笠原信明：人类遗传学。75. 15-18 (1987)

小笠原信明: "Deficiency of erythrocyte type isozyme of AMP deaminase in human(in Purine and Pyrimidine Metabolism in Man V)" Plenum, 5 (1986)

Nobuaki Ogasawara：“人类 AMP 脱氨酶红细胞型同工酶缺乏症（在人类 V 中的嘌呤和嘧啶代谢）”全会，5 (1986)