Willis R C, Kaufman A H, Seegmiller J E
J Biol Chem. 1984 Apr 10;259(7):4157-61.
A purine nucleotide (inosinate) cycle is demonstrated with human lymphoblasts. The lymphoblast requires approximately 50 nmol of purine/10(6) cell increment. When the inosinate cycle is interrupted by the genetic, severe deficiency of either or both purine nucleoside phosphorylase (PNP) or hypoxanthine phosphoribosyltransferase (HPRT), purine accumulates in the culture medium as inosine, guanosine, deoxyinosine, and deoxyguanosine (PNP deficiency or PNP, HPRT deficiency) or hypoxanthine and guanine (HPRT deficiency). This accumulation represents an additional 25 to 32 nmol of purine which must be synthesized per 10(6) cell increment. PNP-deficient lymphoblasts have PPRibP contents characteristic of normal lymphoblasts, about 20 to 25 pmol/10(6) cells. HPRT-deficient lymphoblasts have four times higher PPRibP contents. The lymphoblast deficient for both PNP and HPRT has only a marginal elevation of PPRibP content, 1.5 times normal values. The elevated PPRibP content of HPRT-deficient cells reflects the efficient, unilateral reutilization of the ribose moiety of purine ribonucleotides and is not a cause of purine overproduction. Purine overproduction characterizing PNP-deficient lymphoblasts appears similar to overproduction from deficiency of HPRT, i.e. a break in the inosinate cycle rather than overactive de novo purine synthesis.
在人淋巴母细胞中证实了嘌呤核苷酸（次黄苷酸）循环。淋巴母细胞每增加10⁶个细胞大约需要50 nmol嘌呤。当次黄苷酸循环因嘌呤核苷磷酸化酶（PNP）或次黄嘌呤磷酸核糖转移酶（HPRT）其中之一或两者的遗传性严重缺乏而中断时，嘌呤以肌苷、鸟苷、脱氧肌苷和脱氧鸟苷（PNP缺乏或PNP、HPRT缺乏）或次黄嘌呤和鸟嘌呤（HPRT缺乏）的形式在培养基中积累。这种积累代表每增加10⁶个细胞必须额外合成25至32 nmol嘌呤。PNP缺陷的淋巴母细胞的PPRibP含量具有正常淋巴母细胞的特征，约为20至25 pmol/10⁶个细胞。HPRT缺陷的淋巴母细胞的PPRibP含量高四倍。PNP和HPRT均缺陷的淋巴母细胞的PPRibP含量仅略有升高，为正常值的1.5倍。HPRT缺陷细胞中升高的PPRibP含量反映了嘌呤核糖核苷酸核糖部分的有效、单向再利用，而不是嘌呤过量产生的原因。PNP缺陷的淋巴母细胞中特征性的嘌呤过量产生似乎与HPRT缺乏导致的过量产生相似，即次黄苷酸循环中断而非从头嘌呤合成过度活跃。
