Haney D N, Bunn H F
Proc Natl Acad Sci U S A. 1976 Oct;73(10):3534-8. doi: 10.1073/pnas.73.10.3534.
To determine the mechanism for the formation of hemoglobin A1c (Hb A1c) in vivo, we incubated human hemoglobin with glucose and metabolites of glucose. [14C]Glucose-6-phosphate (G6P) reacted readily with deoxyhemoglobin, and formed a covalent linkage. The reaction rate was considerably reduced in the presence of carbon monoxide or 2,3-diphosphoglycerate (2,3-DPG). Purified G6P hemoglobin had a lowered oxygen affinity and decreased reactivity with 2,3-DPG compared to Hb A. G6P behaved as a 2,3-DPG analog and reacted specifically at the NH2-terminal amino group of the beta chain. In contrast, the interaction of hemoglobin with glucose was much slower, and was unaffected by carbon monoxide or 2,3-DPG. Neither glucose-1-phosphate, fructose-6-phosphate, nor fructose-1,6-diphosphate formed a reaction product with hemoglobin. G6P behaves as an affinity label with the phosphate group forming electrostatic bonds at the 2,3-DPG binding site and the aldehvde group reacting with the NH2-terminal amino group of the beta chain. Thus, G6P hemoglobin may be an intermediate in the conversion of Hb A to Hb A1c.
为了确定体内血红蛋白A1c（Hb A1c）的形成机制，我们将人血红蛋白与葡萄糖及葡萄糖代谢产物一起孵育。[14C]葡萄糖-6-磷酸（G6P）很容易与脱氧血红蛋白反应，并形成共价键。在一氧化碳或2,3-二磷酸甘油酸（2,3-DPG）存在的情况下，反应速率显著降低。与Hb A相比，纯化的G6P血红蛋白的氧亲和力降低，与2,3-DPG的反应性降低。G6P表现为2,3-DPG类似物，特异性地在β链的NH2末端氨基处发生反应。相比之下，血红蛋白与葡萄糖的相互作用要慢得多，且不受一氧化碳或2,3-DPG的影响。葡萄糖-1-磷酸、果糖-6-磷酸和果糖-1,6-二磷酸均未与血红蛋白形成反应产物。G6P作为一种亲和标记物，其磷酸基团在2,3-DPG结合位点形成静电键，醛基与β链的NH2末端氨基反应。因此，G6P血红蛋白可能是Hb A转化为Hb A1c过程中的一个中间体。
