Hellerstein M K, Greenblatt D J, Munro H N
Proc Natl Acad Sci U S A. 1986 Sep;83(18):7044-8. doi: 10.1073/pnas.83.18.7044.
Recent studies have questioned the efficiency with which administered glucose generates hepatic glycogen through the direct nonrecycling route compared with the indirect route from glucose recycled through glycolysis followed by gluconeogenesis. Using fasted and refed rats, we examined the relative access of infused [1-3H]- and [U-14C]glucose by way of these two pathways to liver glycogen and to hepatic glucuronic acid, the latter recovered from the urine as the glucuronide conjugated with administered acetaminophen. In fasted animals and during early refeeding, extensive dilution of administered [3H]- and [14C]glucose recovered in glycogen showed that 60-70% of the labeled glucose had undergone recycling by the indirect route. As refeeding progressed with substantial glycogen deposition, the contribution of the recycling pathway to glycogen and glucuronic acid diminished considerably. Thus, there is a shift in pathways of hepatic glucose utilization as liver glycogen accumulates. Consequently, the ratio of 3H/14C in glucuronic acid was closely correlated with the glycogen content of the liver at sacrifice, indicating that this ratio may prove useful as a noninvasive indicator of liver glycogen concentration. Since glycogen and glucuronic acid are derived by single reactions from UDP-glucose, they should show a common labeling pattern with 3H and 14C under various nutritional conditions. However, detailed analysis of their labeling patterns showed a striking divergence, implying that there must be compartmentation of the UDP-glucose pools leading to each of these end products, either because they are made in separate compartments within the same cell or because each is made in different hepatocyte populations. We favor the former explanation because galactose secreted in glycoproteins shows 3H and 14C labeling patterns similar to those of glucuronic acid conjugated with acetaminophen, and both of these conjugations occur in the endoplasmic reticulum of the liver, whereas most glycogen is present in the cytosol.
与通过糖酵解再经糖异生循环利用的葡萄糖的间接途径相比，近期的研究对经直接非循环途径给予的葡萄糖生成肝糖原的效率提出了质疑。我们使用禁食和再喂食的大鼠，通过这两条途径研究了输注的[1-³H]-和[U-¹⁴C]葡萄糖进入肝糖原和肝葡萄糖醛酸的相对情况，后者作为与给予的对乙酰氨基酚结合的葡萄糖醛酸从尿液中回收。在禁食动物和再喂食早期，糖原中回收的给予的[³H]-和[¹⁴C]葡萄糖大量稀释，表明60 - 70%的标记葡萄糖通过间接途径进行了循环利用。随着再喂食的进行以及糖原大量沉积，循环途径对糖原和葡萄糖醛酸的贡献显著减少。因此，随着肝糖原的积累，肝脏葡萄糖利用途径发生了转变。结果，葡萄糖醛酸中³H/¹⁴C的比值与处死时肝脏的糖原含量密切相关，表明该比值可能作为肝糖原浓度的一种非侵入性指标。由于糖原和葡萄糖醛酸由UDP - 葡萄糖通过单一反应生成，在各种营养条件下它们应呈现³H和¹⁴C的共同标记模式。然而，对它们标记模式的详细分析显示出显著差异，这意味着导致这些终产物的UDP - 葡萄糖池必定存在区室化，要么是因为它们在同一细胞内的不同区室中合成，要么是因为它们在不同的肝细胞群体中合成。我们倾向于前一种解释，因为糖蛋白中分泌的半乳糖呈现出与对乙酰氨基酚结合的葡萄糖醛酸相似的³H和¹⁴C标记模式，并且这两种结合都发生在肝脏的内质网中，而大多数糖原存在于细胞质中。
