Parker N F, Jack I, Van Der Weyden M B
J Lab Clin Med. 1982 May;99(5):731-9.
To evaluate the importance of altered pyrimidine synthesis in the relationship between immune dysfunction and deficiency of ADA, this pathway has been evaluated in normal and ADA-deficient human lymphoblasts. Adenosine and deoxyadenosine effect comparable reductions of radiolabeled bicarbonate incorporation in uridine nucleosides of both normal and deficient cells, with this effect being more prolonged in deficient cells. In ADA-deficient lymphoblasts this altered pyrimidine metabolism is accompanied by reduced intracellular concentrations of PP-ribose-P with adenosine but not deoxyadenosine. The altered PP-ribose-P levels are accompanied by orotic acid accumulation, but this block does not fully account for the net reduction in uridine nucleotide synthesis. This suggests interference of the pyrimidine pathway at another locus, possibly by altered carbamyl phosphate synthetase activity. The mechanism for deoxyadenosine-mediated inhibition is obscure. Despite the demonstrable adenosine- and deoxyadenosine-mediated alterations of pyrimidine metabolism, these changes are not accompanied by marked interference of cell growth for both normal and ADA-deficient lymphoblasts. These data support the hypothesis that altered pyrimidine metabolism is not the basis for the immune disorder in patients with deficiency of ADA.
为了评估嘧啶合成改变在免疫功能障碍与腺苷脱氨酶（ADA）缺乏之间关系中的重要性，已在正常和ADA缺乏的人淋巴母细胞中对该途径进行了评估。腺苷和脱氧腺苷对正常细胞和缺陷细胞尿苷核苷中放射性标记的碳酸氢盐掺入有类似程度的降低作用，且这种作用在缺陷细胞中持续时间更长。在ADA缺乏的淋巴母细胞中，这种嘧啶代谢改变伴随着细胞内PP - 核糖 - P与腺苷而非脱氧腺苷浓度的降低。PP - 核糖 - P水平的改变伴随着乳清酸积累，但这种阻断并不能完全解释尿苷核苷酸合成的净减少。这表明嘧啶途径在另一个位点受到干扰，可能是由于氨基甲酰磷酸合成酶活性改变。脱氧腺苷介导的抑制机制尚不清楚。尽管已证实腺苷和脱氧腺苷介导了嘧啶代谢的改变，但这些变化并未对正常和ADA缺乏的淋巴母细胞的细胞生长产生明显干扰。这些数据支持这样的假设，即嘧啶代谢改变不是ADA缺乏患者免疫紊乱的基础。
