Main Menu

High concentration of galactose-1-phosphate inhibits phospho glucomutase, the enzyme that converts glucose-6-P to glucose-1-P. How can this inhibition account forhypoglycemia and jaundice that accompany galactose-1-P uridyl transferase deficiency in Classical Galactosemia?

Inhibition of Phosphoglucomutase by galactose-1-P results in hypoglycemia due to interference in formation of UDP glucose (Glycogen precursor) and also in the degradation of glycogen back to glucose-6-p.

In the process of Glycogen degradation, 90% of glycogen is converted to Glucose-1-p by the action of Phosphorylase while 10% of the glycogen is degraded to free glucose by debranching enzyme  through its amyloglycosidase component at the branch point. Glucose-1-P gets converted to glucose-6-p by Phosphoglucomutase and  then finally to free glucose by glucose-6 phosphatase so as to contribute to blood glucose level.

In galactosemia (See figure-), due to accumulated Galactose-1-p when Phosphoglucomutase is inhibited less glucose-6-p is formed and hence less free glucose is formed to be exported from liver. Thus stored glycogen is only 10%efficient in raising blood glucose level and hence hypoglycemia results. UDP glucose levels are reduced, because glucose-1-p is required for the formation of UDP glucose. 

Hence in the absence of Phosphoglucomutase activity,glucose-6-p (derived from the activity of glucokinase or from gluconeogenesis),can not be converted to glucose-1-p. This prevents the formation of UDP glucuronic acid which is required to convert bilirubin to bilirubin diglucuronide form for transport in to bile. Bilirubin accumulates in tissues causing jaundice.

Figure-showing inhibition of phosphoglucomutase and Uridyl Transferase by Galactose-1-P
Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

One Response to Hypoglycemia and Jaundice in Galactosemia

  • Dear Students, here you need to revise your concepts of glycogen synthesis, degradation and also the initial steps of Uronic acid pathway till the formation of UDP glucuronic acid so as to understand better the logic explained here.We have done all in detail in the class and hence i do not feel the need to explain again.