In a recent study of 269 GSD-V patients, 39.4% reported no previous episodes of myoglobinuria and 6.8% had normal CK even with fixed muscle weakness, so an absence of myoglobinuria and normal CK should not rule out the possibility of the disease.As skeletal muscle relies predominantly on glycogenolysis for the first few minutes as it transitions from rest to activity, as well as throughout high-intensity aerobic activity and all anaerobic activity, individuals with GSD-V experience during exercise: sinus tachycardia, tachypnea, muscle fatigue and pain, during the aforementioned activities and time frames. Patients may exhibit a “second wind” phenomenon. This is characterized by the patients better tolerance for aerobic exercise such as walking and cycling after approximately 10 minutes. This is attributed to the combination of increased blood flow and the ability of the body to find alternative sources of energy, like fatty acids and proteins. In the long term, patients may exhibit kidney failure due to the myoglobinuria, and with age, patients may exhibit progressively increasing weakness and substantial muscle loss.Younger people may display unusual symptoms, such as difficulty in chewing, swallowing or utilizing normal oral motor functions. A number of comorbidities were found in GSD-V patients at a higher rate than found in the general population, including (but not limited to): hypertension (17%), endocrine diseases (15.7%), muskuloskeletal/rheumatic disease (12.9%), hyperuricemia/gout (11.6%), gastrointestinal diseases (11.2%), neurological disease (10%), respiratory disease (9.5%), and coronary artery disease (8.3%).
The interactions of several amino acids in myophosphorylases structure are known. Ser-14 is modified by phosphorylase kinase during activation of the enzyme. Lys-680 is involved in binding the pyridoxal phosphate, which is the active form of vitamin B6, a cofactor required by myophosphorylase. By similarity, other sites have been estimated: Tyr-76 binds AMP, Cys-109 and Cys-143 are involved in subunit association, and Tyr-156 may be involved in allosteric control. Function
Myophosphorylase is the form of the glycogen phosphorylase found in muscle that catalyses the following reaction:((1→4)-alpha-D-glucosyl) (n) + phosphate = ((1→4)-alpha-D-glucosyl) (n-1) + alpha-D-glucose 1-phosphate
Failure of this enzyme ultimately impairs the operation of ATPases. This is due to the lack of normal pH fall during exercise, which impairs the creatine kinase equilibrium and exaggerates the rise of ADP. Pathophysiology
Myophosphorylase is involved in the breakdown of glycogen to glucose for use in muscle. The enzyme removes 1,4 glycosyl residues from outer branches of glycogen and adds inorganic phosphate to form glucose-1-phosphate. Ordinarily, the removal of 1,4 glycosyl residues by myophosphorylase leads to the formation of glucose-1-phosphate during glycogen breakdown and the polar, phosphorylated glucose cannot leave the cell membrane and so is marked for intracellular catabolism. In McArdles Disease, deficiency of myophosphorylase leads to accumulation of intramuscular glycogen and a lack of glucose-1-phosphate for cellular fuel. Myophosphorylase exists in the active form when phosphorylated. The enzyme phosphorylase kinase plays a role in phosphorylating glycogen phosphorylase to activate it and another enzyme, protein phosphatase-1, inactivates glycogen phosphorylase through dephosphorylation.