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Mol Aspects Med. 2015 Dec;46:34-45. doi: 10.1016/j.mam.2015.09.002. Epub 2015 Oct 28.

Role of glycogen phosphorylase in liver glycogen metabolism.

Author information

1
Institutes of Cellular Medicine and Ageing and Health, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. Electronic address: loranne.agius@ncl.ac.uk.

Abstract

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.

KEYWORDS:

Glucose; Glucose 6-phosphate; Glycogen targeting proteins; Insulin; Liver; PPP1R3B; PPP1R3C; Phosphorylase

PMID:
26519772
DOI:
10.1016/j.mam.2015.09.002
[Indexed for MEDLINE]

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