Gopher A, Vaisman N, Mandel H, Lapidot A
Department of Isotope Research, Weizmann Institute of Science, Rehovot, Israel.
Proc Natl Acad Sci U S A. 1990 Jul;87(14):5449-53. doi: 10.1073/pnas.87.14.5449.
An inborn deficiency in the ability of aldolase B to split fructose 1-phosphate is found in humans with hereditary fructose intolerance (HFI). A stable isotope procedure to elucidate the mechanism of conversion of fructose to glucose in normal children and in HFI children has been developed. A constant infusion of D-[U-13C]fructose was given nasogastrically to control and to HFI children. Hepatic fructose conversion to glucose was estimated by examination of 13C NMR spectra of plasma glucose. The conversion parameters in the control and HFI children were estimated on the basis of doublet/singlet values of the plasma beta-glucose C-1 splitting pattern as a function of the rate of fructose infusion (0.26-0.5 mg/kg per min). Significantly lower values (approximately 3-fold) for fructose conversion to glucose were obtained for the HFI patients as compared to the controls. A quantitative determination of the metabolic pathways of fructose conversion to glucose was derived from 13C NMR measurement of plasma [13C]glucose isotopomer populations. The finding of isotopomer populations of three adjacent 13C atoms at glucose C-4 (13C3-13C4-13C5) suggests that there is a direct pathway from fructose, by-passing fructose-1-phosphate aldolase, to fructose 1,6-bisphosphate. The metabolism of fructose by fructose-1-phosphate aldolase activity accounts for only approximately 50% of the total amount of hepatic fructose conversion to glucose. It is suggested that phosphorylation of fructose 1-phosphate to fructose 1,6-bisphosphate by 1-phosphofructokinase occurs in human liver (and intestine) when fructose is administered nasogastrically; 47% and 27% of the total fructose conversion to glucose in controls and in HFI children, respectively, takes place by way of this pathway. In view of the marked decline by 67% in synthesis of glucose from fructose in HFI subjects found in this study, the extent of [13C]glucose formation from a "trace" amount (approximately 20 mg/kg) of [U-13C]fructose infused into the patient can be used as a safe and noninvasive diagnostic test for inherent faulty fructose metabolism.
遗传性果糖不耐受（HFI）患者体内存在醛缩酶B分解1-磷酸果糖能力的先天性缺陷。现已开发出一种稳定同位素方法，用于阐明正常儿童和HFI儿童中果糖转化为葡萄糖的机制。通过鼻胃管向对照组和HFI儿童持续输注D-[U-13C]果糖。通过检测血浆葡萄糖的13C NMR谱来估计肝脏中果糖向葡萄糖的转化。根据血浆β-葡萄糖C-1分裂模式的双峰/单峰值作为果糖输注速率（0.26 - 0.5 mg/kg每分钟）的函数，来估计对照组和HFI儿童的转化参数。与对照组相比，HFI患者果糖转化为葡萄糖的值显著降低（约3倍）。通过对血浆[13C]葡萄糖异构体群体的13C NMR测量，定量测定了果糖转化为葡萄糖的代谢途径。在葡萄糖C-4处发现三个相邻13C原子的异构体群体（13C3 - 13C4 - 13C5）表明，存在一条从果糖直接绕过1-磷酸果糖醛缩酶到1,6-二磷酸果糖的途径。通过1-磷酸果糖醛缩酶活性进行的果糖代谢仅占肝脏中果糖转化为葡萄糖总量的约50%。有人提出，当通过鼻胃管给予果糖时，人肝脏（和肠道）中1-磷酸果糖激酶将1-磷酸果糖磷酸化为1,6-二磷酸果糖；在对照组和HFI儿童中，分别有47%和27%的果糖转化为葡萄糖是通过这条途径进行的。鉴于本研究中发现HFI受试者中果糖合成葡萄糖的量显著下降67%，向患者输注“微量”（约20 mg/kg）[U-13C]果糖后[13C]葡萄糖的生成程度可作为一种安全、无创的固有果糖代谢缺陷诊断测试。
