Muscle Glycogen Phosphorylase and Its Functional Partners in Health and Disease.

Glycogen phosphorylase (PG) is a key enzyme taking part in the first step of glycogenolysis. Muscle glycogen phosphorylase (PYGM) differs from other PG isoforms in expression pattern and biochemical properties. The main role of PYGM is providing sufficient energy for muscle contraction. However, it is expressed in tissues other than muscle, such as the brain, lymphoid tissues, and blood. PYGM is important not only in glycogen metabolism, but also in such diverse processes as the insulin and glucagon signaling pathway, insulin resistance, necroptosis, immune response, and phototransduction. PYGM is implicated in several pathological states, such as muscle glycogen phosphorylase deficiency (McArdle disease), schizophrenia, and cancer. Here we attempt to analyze the available data regarding the protein partners of PYGM to shed light on its possible interactions and functions. We also underline the potential for zebrafish to become a convenient and applicable model to study PYGM functions, especially because of its unique features that can complement data obtained from other approaches.

GPH1 is involved in glycerol accumulation in the three-dimensional networks of the nematode-trapping fungus Arthrobotrys oligospora.

Turgor is very important for the invasive growth of fungal pathogens. Glycerol, a highly osmotic solvent, is considered to play an important role in turgor generation. The nematophagous fungus Arthrobotrys oligospora mainly lives as a saprophyte. In the presence of nematodes, A. oligospora enters the parasitic stage by forming three-dimensional networks (traps) to capture nematodes. In A. oligospora, we found that glycerol accumulated during nematode-induced trap formation. We demonstrated that deleting gph1, which encodes glycogen phosphorylase, decreased the glycerol content, compared with that of a wild-type strain. Although the number of traps induced by nematodes was not affected in the Δgph1 mutant, the capture rate was lower. Meanwhile, deleting gph1 also affected the growth rate and conidiation capacity of the fungus. These results indicate that glycerol derived from GPH1 is essential for the full virulence of A. oligospora against nematodes.

Respiration accumulates Calvin cycle intermediates for the rapid start of photosynthesis in Synechocystis sp. PCC 6803.

We tested the hypothesis that inducing photosynthesis in cyanobacteria requires respiration. A mutant deficient in glycogen phosphorylase (∆GlgP) was prepared in Synechocystis sp. PCC 6803 to suppress respiration. The accumulated glycogen in ΔGlgP was 250-450% of that accumulated in wild type (WT). The rate of dark respiration in ΔGlgP was 25% of that in WT. In the dark, P700(+) reduction was suppressed in ΔGlgP, and the rate corresponded to that in (2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone)-treated WT, supporting a lower respiration rate in ∆GlgP. Photosynthetic O2-evolution rate reached a steady-state value much slower in ∆GlgP than in WT. This retardation was solved by addition of d-glucose. Furthermore, we found that the contents of Calvin cycle intermediates in ∆GlgP were lower than those in WT under dark conditions. These observations indicated that respiration provided the carbon source for regeneration of ribulose 1,5-bisphosphate in order to drive the rapid start of photosynthesis.

Oxidative stress and chronological aging in glycogen-phosphorylase-deleted yeast.

Chronological aging in yeast resembles aging in mammalian, postmitotic tissues. Such chronological aging begins with entrance into the stationary phase after the nutrients are exhausted. Many changes in metabolism take place at this moment, and survival in this phase strongly depends on oxidative-stress resistance. In this study, hypo- and hyperglycogenic phenotypes of Saccharomyces cerevisiae strains with deletions of carbohydrate-metabolism enzymes were selected, and a comparison of their chronological longevities was made. Stress sensitivity, ROS, and apoptosis markers during aging were analyzed in the emerged candidates. Among the strains that accumulated greater amounts of glycogen, the deletion of glycogen phosphorylase, gph1delta, was unique in showing a shortened life span, stress intolerance, and higher levels of ROS during its survival. The transcription of superoxide dismutase genes during survival was three- to fourfold lower in gph1delta. Extra copies of SOD1/2 counteracted the stress sensitivity and the accelerated aging of gph1delta. In conclusion, the lack of gph1 produced a rapidly aging strain, which could be attributed, at least in part, to the weakened stress resistance associated with the decreased expression of both SODs. Gph1p seems to be a candidate in a scenario that could link early metabolic changes with other targets of the stress response during stationary-phase survival.

A 1-year-old infant with McArdle disease associated with hyper-creatine kinase-emia during febrile episodes.

A 14-month-old girl was hospitalized due to repeated hyper-creatine kinase (CK)-emia during pyrexia. Mild hypotonia was observed, but other physical and neurological findings were unremarkable. The serum CK level was normal at rest or normothermia. Open muscle biopsy was performed on the rectus femoris, and showed glycogen storage and complete lack of phosphorylase activity histochemically and biochemically, establishing the diagnosis of McArdle disease. The diagnosis of McArdle disease in early infancy is uncommon. Until this study there have been no reports of clinical symptoms or muscle biopsy findings for McArdle disease in early childhood. This disease must be considered when transient hyper-CKemia is observed in infants, even if glycogen storage is unremarkable as compared with adult cases.