In: Biology
A patient has glycogen storage disease. They are 2 months old. She is hypoglycemic despite being fed every two hours. When epinephrine is administered, why is there is an increase in blood lactate?
Glycogen storage disease type I (GSD-I; Von Gierke disease) is an autosomal recessive inborn error of carbohydrate metabolism caused by defects of the glucose-6-phosphatase (G6Pase) complex. G6Pase catalyzes the hydrolysis of glucose-6-phosphate (G6P) to glucose and phosphate in the terminal steps of gluconeogenesis and glycogenolysis. The genes responsible for GSD I include are G6Pase and G6P transporter genes. G6Pase deficiency results in excessive accumulation of glycogen in the liver and kidney, leading to progressive hepatomegaly and renal enlargement. As in liver glucose is formed by lactate, but because glucose is not formed, lactate amount increases. Lactic acidosis (high lactic acid) occurs as lactate generated during hepatic glycolysis cannot be converted to glucose. Epinephrine is responsible for glycogen breakdown into G1P but as G6Pase is mutated instead of glucose, lactate is produced, cause increase in lactate concentration and thus lactic acidosis.
The decrease in glucose level in blood cause hypoglycemia and leads to the elevation of plasma glucagon levels, activating glycogen phosphorylase.The activation promotes the further elevation of G6P levels, resulting in a decrease of intrahepatic phosphate that inhibits AMP deaminase. This decrease stimulates AMP deaminase, resulting in the degradation of adenine nucleotides and consequent overproduction of uric acid. Lactic acidosis and ketonemia also decreases renal uric acid excretion by stimulation of uric acid reabsorption.