Question

Congenital defects in glycogen metabolism can have serious negative effects on human health. Below are several examples taken from box 15.4 in the text. For each example, state how glucose glycogen metabolism is likely altered from an inherited mutation to the stated enzyme (assume these mutations cause the enzymes to lose their normal function).

1. The “Type 0” glycogen storage disease (liver) is caused by glycogen synthase (GYS). Symptoms include low blood glucose, high ketone bodies, early death.
2. The “Type Ia (Von Gierke)” glycogen storage disease (liver) is caused by Glucose 6-phosphatase. Symptoms include enlarged liver and kidney failure.
3. The “Type VII (Tarui)” glycogen storage disease (muscle) is caused by PFK-1. Symptoms include muscle exercise cramps.

Please answer with explanation. Thank you!

Answer 1

Type O (Liver glycogen storage disease):

This is caused by the deficiency of glycogen synthase in the liver. This leads to accumulation glucose in the blood (hyperglycemia). Glycogen structure will be normal, but present in very little quantity. High levels of blood glucose stimulates high rate of glycolysis.

Type Ia (von Gierke’s disease):

This is caused by the deficiency of glucose-6-phosphatase in the liver. This enzyme catalyses the last step of glycogenolysis/gluconeogenesis (conversion of glucose-6-phsophate to glucose) leading to release of free glucose into bloodstream. Lack of glucose-6-phosphatase leads to build-up of glucose-6-phosphate which in turn enters glycogenesis. Glucose-6-phosphate (G6P) also stimulates glycogen synthase activity. This disease also causes hypoglycaemia as the glucose units derived from glycogen are not able to enter the blood stream.

Type VII (Tarui’s disease):

This disease is caused by the deficiency of phosphofructokinase (PFK) in the muscle. This is a glycolytic enzyme converting fructose-6-phsophate (F6P) into fructose-1,6-bisphosphate. Lack of PFK leads to accumulation of F6P and G6P which leads to increased glycogenesis via glycogen synthase. In this disease, there is an accumulation of glycogen in the muscle.