Regulatory phosphorylation event of phosphoglucomutase 1 tunes its activity to regulate glycogen metabolism

Abstract

Regulation of glycogen metabolism is of vital importance in organisms of all three kingdoms of life. Although the pathways involved in glycogen synthesis and degradation are well known, many regulatory aspects around the metabolism of this polysaccharide remain undeciphered. Here, we used the unicellular cyanobacterium Synechocystis as a model to investigate how glycogen metabolism is regulated in nitrogen-starved dormant cells, which entirely rely on glycogen catabolism to resume growth upon nitrogen repletion. We identified phosphoglucomutase 1 (PGM1) as a key regulatory point in glycogen metabolism, and post-translational modification as an essential mechanism for controlling its activity. We could show that PGM1 is phosphorylated ata residue in the regulatory latch domain (Ser 47) during nitrogen starvation, which inhibits its activity. Inactivation of PGM1 by phosphorylation at Ser 47 prevents premature degradation of the glycogen stores and appears to be essential for survival of Synechocystis in the dormant state. Remarkably, this regulatory mechanism seems to be evolutionary conserved in PGM1 enzymes, from bacteria to humans.

Impact of the carbon flux regulator protein pirC on ethanol production in engineered cyanobacteria

“…In addition to ethanol, we also quantified several key metabolites to get an impression about the impact of ethanol production on the entire carbon and nitrogen metabolism in the different strains. Glycogen represents the major high molecular mass carbon storage and becomes particularly accumulated under excess carbon supply, i.e., under high CO 2 conditions ( Eisenhut et al, 2007 ) or after strong nitrogen limitations ( Doello et al, 2022 ). When grown at 250 μmol photons m −2 s −1 , only cells of the WT accumulated substantial amounts of glycogen, whereas the ethanol-producing strains WT 219 and ∆ pirC 219 were virtually free of glycogen ( Figure 5A ).…”

Effect of chronic heat stress on the carbonylation of glycolytic enzymes in breast muscle and its correlation with the growth performance of broilers

“…PGM1 is the major evolutionary conserved enzyme in catalyzing glycogen catalysis. Its carbonylation by heat exposure may induce further dephosphorylation at peripheral residues via conformational change, which accelerates glycogenolysis ( Doello et al, 2022 ). TPI is responsible for the net gain of glycolysis-derived ATP by catalyzing the interconversion between glyceraldehyde-3-phosphate ( GA3P ) and dihydroxyacetone phosphate ( DHAP ) ( Olivares-Illana et al, 2017 ).…”

Glycogen synthesis prevents metabolic imbalance and disruption of photosynthetic electron transport from photosystem II during transition to photomixotrophy in Synechocystis sp. PCC 6803

“…G1P is then coupled with ATP to produce ADP‐glucose by ADP‐glucose pyrophosphorylase (AGP), which is used by glycogen synthase(s) (GlgA) to elongate the glycogen chains (Ball & Morell, 2003; Cifuente et al ., 2019). Strains deficient in either AGP or PGM, which contain null or reduced glycogen levels, respectively, are viable under permissive conditions (Gründel et al ., 2012; Doello et al ., 2022; Ortega‐Martínez et al ., 2023).…”