Institutes of Cellular Medicine and Ageing and Health, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Mol Aspects Med. 2015 Dec;46:34-45. doi: 10.1016/j.mam.2015.09.002. Epub 2015 Oct 28.
Liver glycogen is synthesized after a meal in response to an increase in blood glucose concentration in the portal vein and endocrine and neuroendocrine signals, and is degraded to glucose between meals to maintain blood glucose homeostasis. Glycogen degradation and synthesis during the diurnal cycle are mediated by changes in the activities of phosphorylase and glycogen synthase. Phosphorylase is regulated by phosphorylation of serine-14. Only the phosphorylated form of liver phosphorylase (GPa) is catalytically active. Interconversion between GPa and GPb (unphosphorylated) is dependent on the activities of phosphorylase kinase and of phosphorylase phosphatase. The latter comprises protein phosphatase-1 in conjunction with a glycogen-targeting protein (G-subunit) of the PPP1R3 family. At least two of six G-subunits (GL and PTG) expressed in liver are involved in GPa dephosphorylation. GPa to GPb interconversion is dependent on the conformational state of phosphorylase which can be relaxed (R) or tense (T) depending on the concentrations of allosteric effectors such as glucose, glucose 6-phosphate and adenine nucleotides and on the acetylation state of lysine residues. The G-subunit, GL, encoded by PPP1R3B gene is expressed at high levels in liver and can function as a phosphorylase phosphatase and a synthase phosphatase and has an allosteric binding site for GPa at the C-terminus which inhibits synthase phosphatase activity. GPa to GPb conversion is a major upstream event in the regulation of glycogen synthesis by glucose, its downstream metabolites and extracellular signals such as insulin and neurotransmitters.
肝糖原在餐后会合成，以响应门静脉中血糖浓度的增加以及内分泌和神经内分泌信号，并且在两餐之间会降解为葡萄糖，以维持血糖稳态。昼夜节律中糖原的降解和合成是通过磷酸化酶和糖原合酶活性的变化来介导的。磷酸化酶受丝氨酸-14 的磷酸化调节。只有磷酸化的肝磷酸化酶（GPa）形式具有催化活性。GPa 与 GPb（未磷酸化）之间的相互转化依赖于磷酸化酶激酶和磷酸化酶磷酸酶的活性。后者由蛋白磷酸酶-1 与 PPP1R3 家族的糖原靶向蛋白（G 亚基）组成。在肝脏中表达的六个 G 亚基（GL 和 PTG）中的至少两个参与了 Ga 的去磷酸化。GPa 到 GPb 的相互转化依赖于磷酸化酶的构象状态，该状态可以根据别构效应物（如葡萄糖、葡萄糖 6-磷酸和腺嘌呤核苷酸）的浓度以及赖氨酸残基的乙酰化状态而松弛（R）或紧张（T）。由 PPP1R3B 基因编码的 G 亚基 GL 在肝脏中高表达，可作为磷酸化酶磷酸酶和糖原合酶磷酸酶发挥作用，并且在 C 末端具有与 Ga 的别构结合位点，该结合位点抑制了合酶磷酸酶的活性。Ga 到 GPb 的转化是葡萄糖及其下游代谢物以及细胞外信号（如胰岛素和神经递质）调节糖原合成的主要上游事件。
