Muscle Metabolism Flashcards
Primary purposes of skeletal muscle
Contraction to perform work (must make ATP), return plasma glucose levels to homeostasis following a carbohydrate meal
Skeletal muscle response to a carbohydrate meal
Insulin binds insulin receptor, GLUT-4 goes to cell surface to bind glucose, then glucose-6-phosphate can be stored as glycogen (when ATP levels are sufficient) or used in glycolysis/TCA/ETC to make ATP
Endocrine hormonal response to carbohydrate meal
Fasted state: Glucose low, insulin low, glucagon high
Fed state: Glucose high, insulin high, glucagon low
Fuel source during exercise and fasting
Muscle glycogen used for the first hour or so, then blood-borne fatty acids and glucose can be used
Muscle metabolism during fasting or exercise with glycogen
Epinephrine binds receptor on cell to activate the phosphorylation of glycogen into glucose-6-phopshate with the coactivation of AMP and Ca2+ to continue through glycolysis/TCA/ETC and produce ATP, in anaerobic conditions, lactate is made from pyruvate
Muscle metabolism during fasting or exercise without glycogen
Fatty acids utilized using a FATP and converted into fatty acyl-CoA, then in the mitochondrial outer membrane is bound by carnitine to take into inner membrane, where it is turned back into FA-CoA and then into acetyl-CoA through beta oxidation for use in the TCA/ETC to make ATP
Normal liver and muscle function
Liver can make and store glycogen from glucose and then release when needed to go to the muscles as glucose, which can also make and store glycogen, or can use the glucose in glycolysis/TCA/ETC to create ATP
Glycogen storage disease basic mechanism - hepatic type
Liver cannot turn glycogen into glucose anymore, resulting in low blood glucose
Glycogen storage disease basic mechanism - myopathic type
Glycogen cannot be metabolized in muscle so no ATP can be made in the absence of glucose, leading to low energy output
Enzyme deficient in von Gierke’s disease
Glucose-6-phosphatase
Enzyme deficient in Cori’s disease
Glycogen debrancher
Enzyme deficient in McArdle disease
Muscle glycogen phosphorylase
Enzyme deficient in Hers’ disease
Liver glycogen phosphorylase
Enzyme deficient in Pompe’s disease
Acid maltase (alpha 1,4-glucosidase)
Hepatic forms of glycogen storage diseases
Von Gierke’s, Cori’s, Hers’
Muscle forms of glycogen storage diseases
Pompe’s, McArdle’s
Von Gierke’s clinical presentation
Massive hepatomegaly, short stature, failure to thrive, severe hypoglycemia, retinal lesions
Von Gierke’s laboratory findings
Increased lactate, pyruvate, triglycerides, cholesterol, uric acid in serum, decreased enzyme activity of increased glycogen levels on liver biopsy
Cori’s clinical presentation
Similar presentation as von Gierke’s but less severe (hepatomegaly, short stature, hypoglycemia, retinal lesions)
Cori’s laboratory findings
Normal lactate and uric acid, cholesterol, triglycerides in serum, can only be diagnosed with enzyme assay
Hers’ clinical presentation
Mild hepatomegaly, mild hypoglycemia
Hers’ laboratory findings
Minimal, increased liver glycogen
Pompe’s clinical presentation
Massive cardiomegaly, hypotonia, early death from cardiorespiratory failure, milder forms in adults
Pompe’s laboratory findings
Increased CPK levels
McArdle’s clinical presentation
Exercise-induced muscle pain and cramps, rhabdomyolysis
McArdle’s laboratory findings
Increased CPK with episodes, no blood lactate with exercise, increased glycogen and decreased enzyme activity on muscle biopsy
