A 31-year-old man comes to the office for a routine checkup. He has no significant medical problems and does not take any medications. The patient works as a fitness trainer and lifts weights recreationally. He has been consuming carbohydrate-rich food prior to his weightlifting sessions and claims that it increases muscle strength. A literature review shows that the rate of glycogenolysis within myocytes increases several hundredfold during active skeletal muscle contraction. Which of the following substances is most likely responsible for increasing the reaction rate during active contraction?

Question

A 31-year-old man comes to the office for a routine checkup.  He has no significant medical problems and does not take any medications.  The patient works as a fitness trainer and lifts weights recreationally.  He has been consuming carbohydrate-rich food prior to his weightlifting sessions and claims that it increases muscle strength.  A literature review shows that the rate of glycogenolysis within myocytes increases several hundredfold during active skeletal muscle contraction.  Which of the following substances is most likely responsible for increasing the reaction rate during active contraction?

Quizplus · Accepted Answer

11ec160b_36b7_d05f_9249_f3df32fc6e84_MD0001_00 Glycogen is broken down by the enzyme glycogen phosphorylase, which is regulated through phosphorylation (active state) and dephosphorylation (inactive state). Phosphorylase kinase (PK) is the enzyme responsible for the phosphorylation of glycogen phosphorylase, whereas phosphoprotein phosphatase catalyzes its dephosphorylation. PK is regulated differently in liver than in muscles. Glycogen stored in the liver is used to maintain blood glucose levels during the fasting state, whereas glycogen in the muscles is used to provide energy for muscle contraction. In the liver, PK is activated primarily through the binding of epinephrine and glucagon to G_s protein-coupled receptors, which increases cAMP concentrations and causes phosphorylation of PK (via protein kinase A). Skeletal muscle lacks glucagon receptors, but muscle PK can still be phosphorylated in response to an epinephrine-induced increase in cAMP concentrations. However, increased intracellular calcium is a more powerful activator of muscle PK. Release of sarcoplasmic calcium stores following neuromuscular acetylcholine stimulation allows for synchronization of skeletal muscle contraction and glycogen breakdown, providing the energy necessary for anaerobic muscle contraction. (Choices A and D) Phosphorylated glycogen phosphorylase (active form) is allosterically inhibited by ATP and glucose-6-phosphate in both liver and muscle cells. Increased intracellular ATP levels help to decrease the rate of glycogenolysis upon cessation of active muscle contraction. (Choice C) Although increased cAMP stimulates muscle glycogen breakdown via the action of epinephrine on beta-1 adrenergic receptors, it is not responsible for synchronization of active muscle contraction and glycogen breakdown. (Choice E) Lactate is produced in tissues during anaerobic glycolysis, such as in muscles during strenuous exercise as a result of relatively hypoxic conditions. The lactate produced by the muscles can be converted to glucose in the liver via gluconeogenesis. Educational objective: Synchronization of glycogen degradation with skeletal muscle contraction occurs due to release of sarcoplasmic calcium following neuromuscular stimulation. Increased intracellular calcium causes activation of phosphorylase kinase, stimulating glycogen phosphorylase to increase glycogenolysis. __________ References: Muscle glycogenolysis. Regulation of the cyclic interconversion of phosphorylase a and phosphorylase b. (http://www.ncbi.nlm.nih.gov/pubmed/1899238)

A 31-Year-Old Man Comes to the Office for a Routine