Carabaza A, Ricart M D, Mor A, Guinovart J J, Ciudad C J
Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, Bellaterra, Spain.
J Biol Chem. 1990 Feb 15;265(5):2724-32.
The mechanism for glycogen synthesis stimulation produced by adenosine, fructose, and glutamine has been investigated. We have analyzed the relationship between adenine nucleotides and glycogen metabolism rate-limiting enzymes upon hepatocyte incubation with these three compounds. In isolated hepatocytes, inhibition of AMP deaminase with erythro-9-(2-hydroxyl-3nonyl)adenine further increases the accumulation of AMP and the activation of glycogen synthase and phosphorylase by fructose. This ketose does not increase cyclic AMP or the activity of cyclic AMP-dependent protein kinase. Adenosine raises AMP and ATP concentration. This nucleotide also activates glycogen synthase and phosphorylase by covalent modification. The correlation coefficient between AMP and glycogen synthase activity is 0.974. Nitrobenzylthioinosine, a transport inhibitor of adenosine, blocks (by 50%) the effect of the nucleoside on AMP formation and glycogen synthase but not on phosphorylase. 2-Chloroadenosine and N6-phenylisopropyladenosine, nonmetabolizable analogues of adenosine, activate phosphorylase (6-fold) without increasing the concentration of adenine nucleotides or the activity of glycogen synthase. Cyclic AMP is not increased by adenosine in hepatocytes from starved rats but is in cells from fed animals. [Ethylenebis (oxyethylenenitrilo)]tetraacetic acid (EGTA) blocks by 60% the activation of phosphorylase by adenosine but not that of glycogen synthase. Glutamine also increases AMP concentration and glycogen synthase and phosphorylase activities, and these effects are blocked by 6-mercaptopurine, a purine synthesis inhibitor. Neither adenosine nor glutamine increases glucose 6-phosphate. It is proposed that the observed efficient glycogen synthesis from fructose, adenosine, and glutamine is due to the generation of AMP that activates glycogen synthase probably through increases in synthase phosphatase activity. It is also concluded that the activation of phosphorylase by the above-mentioned compounds can be triggered by metabolic changes.
已对腺苷、果糖和谷氨酰胺刺激糖原合成的机制进行了研究。我们分析了在肝细胞与这三种化合物共同孵育时，腺嘌呤核苷酸与糖原代谢限速酶之间的关系。在分离的肝细胞中，用赤藓红-9-(2-羟基-3-壬基)腺嘌呤抑制AMP脱氨酶可进一步增加AMP的积累以及果糖对糖原合酶和磷酸化酶的激活作用。这种酮糖不会增加环磷酸腺苷（cAMP）或cAMP依赖性蛋白激酶的活性。腺苷可提高AMP和ATP的浓度。这种核苷酸还通过共价修饰激活糖原合酶和磷酸化酶。AMP与糖原合酶活性之间的相关系数为0.974。腺苷转运抑制剂硝基苄基硫代肌苷可阻断（50%）核苷对AMP形成和糖原合酶的作用，但对磷酸化酶无此作用。2-氯腺苷和N6-苯异丙基腺苷是腺苷的不可代谢类似物，它们可激活磷酸化酶（6倍），但不会增加腺嘌呤核苷酸的浓度或糖原合酶的活性。饥饿大鼠的肝细胞中，腺苷不会增加cAMP，但喂食动物的细胞中会增加。[乙二胺双(氧亚乙基腈)]四乙酸（EGTA）可阻断腺苷对磷酸化酶60%的激活作用，但对糖原合酶无此作用。谷氨酰胺也会增加AMP浓度以及糖原合酶和磷酸化酶的活性，而嘌呤合成抑制剂6-巯基嘌呤可阻断这些作用。腺苷和谷氨酰胺均不会增加6-磷酸葡萄糖。有人提出，观察到的由果糖、腺苷和谷氨酰胺高效合成糖原是由于生成了AMP，其可能通过增加合酶磷酸酶活性来激活糖原合酶。还得出结论，上述化合物对磷酸化酶的激活可能由代谢变化引发。
