Question

McArdle Disease (glycogen storage disease 5) is caused by mutations in the phosphorylase enzyme in muscle. The symptoms are muscle cramps, pain, and fatigue during strenuous exercise. A) An ischemic exercise test is often used as part of the diagnostic process. This test measures lactate in the blood but is not always specific for McArdle. Explain why lactate might be a good diagnostic measurement for this disease and how its production is regulated in muscle in a normal person versus a McArdle patient. B) A patient is undergoing an ischemic exercise test and is fed 13C glucose prior to the test and then blood is drawn after the test. Explain how the following substrates would be labeled 1) alpha-ketoglutarate, 2) glucose 3) ribose, and 4) alanine. C) in patients with McArdle would you expect electron chain activity to increase, decrease, or remain the same in the muscle cell if the person is at rest? exercising?

Answer 1

Solution :

McArdle disease is an inherited disorder caused by an inability to break down a complex sugar called glycogen in muscle cells It was known as Glycogen storage disease

A)For this McArdle disease an ischemic exercise test is often used as part of the diagnostic process by measuring the amount of lactate. In this disorder glycogenolysis is stopped and then breakdown of glycogen to glucose is not processed. Monocarboxylate transporter MCT1 is used to up regulate in muscles as a result of high levels of lactate in the muscles and low level of lactate in the serum of the patient results in muscles glycolytic block.

B)The splitting up of glucose molecule into 3 carbon pyruvate is known to be glycolysis, and the product obtained in the glycolysis is coverted to alpha keto glutarate , then entering into the krebs cycle carrying the carbon. This carbon is incorporated in ribose when it enters the pentose phosphate pathway . Alanine remains unlabelled. this is considered to be an ischemic test.

C).In Mc Ardles disease the glucose production in absent due to decreased absence of glycogen phoshorylase enzyme. ETC utilises a source of energy for ATP generation. Hence electron transport chain activity remains same and patients derive energy by fatty acid oxidationduring rest,Muscle cells need energy i.e., ATP for contraction and relaxation. in this condition people breathe leads to heavily to rise the blood flow by bringing more glucose to blood, then By ETC more ATP is generated by glucose metabolism.