Nuttall F Q, Gilboe D P, Gannon M C, Niewoehner C B, Tan A W
Section of Endocrinology, Metabolism, Veterans Administration Medical Center, Minneapolis, Minnesota 55417.
Am J Med. 1988 Nov 28;85(5A):77-85. doi: 10.1016/0002-9343(88)90400-7.
The glycogen synthase-mediated reaction is rate-limiting for glycogen synthesis in the liver. Glycogen synthase has been purified essentially to homogeneity and has been shown to be a dimer composed of identical subunits. It is regulated by a phosphorylation-dephosphorylation mechanism, catalyzed by kinases and a phosphatase. The subunits of synthase D, the most phosphorylated form, each contain approximately 17 phosphates. The subunits of synthase I, the least phosphorylated form, each contain 14 phosphates. Thus, during the transition between these two forms, a net of three phosphoryl groups is added or removed. In synthase D, six of the phosphates are alkali-labile. In synthase I, three of the phosphates are alkali-labile. Therefore, all of the phosphorylation sites important in the interconversion of these two forms are alkali-labile (attached to serine or threonine residues). In short-term experiments using isolated hepatocytes, [32P]phosphate was only incorporated into the alkali-labile sites and the phosphate in these sites was shown to turn over rapidly. Glucose addition, which is known to reduce the proportion of synthase in the D form when assayed kinetically, also reduced the [32P]phosphate content. Glucagon addition, which increases the proportion of synthase in the D form, increased it. These changes do not appear to be site-specific. Ingestion or administration of fructose, or galactose, as well as glucose, result in a shift in synthase equilibrium in favor of the less phosphorylated forms. Possible mechanisms by which synthase phosphatase activity may be increased after ingestion of glucose or fructose, and thus shift the equilibrium in favor of the less phosphorylated forms, are discussed. The mechanism by which galactose may stimulate the phosphatase reaction is completely unknown.
糖原合酶介导的反应是肝脏中糖原合成的限速步骤。糖原合酶已基本上纯化至同质，并已证明是由相同亚基组成的二聚体。它通过激酶和磷酸酶催化的磷酸化-去磷酸化机制进行调节。合酶D是磷酸化程度最高的形式，其亚基每个含有约17个磷酸基团。合酶I是磷酸化程度最低的形式，其亚基每个含有14个磷酸基团。因此，在这两种形式之间的转变过程中，净增加或去除了三个磷酰基。在合酶D中，六个磷酸基团对碱不稳定。在合酶I中，三个磷酸基团对碱不稳定。因此，这两种形式相互转化中重要的所有磷酸化位点对碱都不稳定（连接到丝氨酸或苏氨酸残基上）。在使用分离的肝细胞进行的短期实验中，[32P]磷酸盐仅掺入对碱不稳定的位点，并且这些位点中的磷酸盐显示出快速周转。添加葡萄糖在动力学测定时已知会降低合酶D形式的比例，同时也降低了[32P]磷酸盐含量。添加胰高血糖素会增加合酶D形式的比例，使其升高。这些变化似乎不是位点特异性的。摄入或给予果糖、半乳糖以及葡萄糖都会导致合酶平衡向磷酸化程度较低的形式转变。讨论了摄入葡萄糖或果糖后合酶磷酸酶活性可能增加从而使平衡向磷酸化程度较低的形式转变的可能机制。半乳糖刺激磷酸酶反应的机制完全未知。
