Galactose Metabolism Lecture Notes PDF

Lippincott’s illustrated reviews Lecture 24 Galactose Metabolism 1  Specific Objectives By the end of this lecture students can be able to: Explain the metabolic pathway of galactose. Discuss the main disorders in galactose meta...

Lippincott’s illustrated reviews Lecture 24 Galactose Metabolism 1  Specific Objectives By the end of this lecture students can be able to: Explain the metabolic pathway of galactose. Discuss the main disorders in galactose metabolism. 2  Galactose Metabolism The main source of galactose is lactose (milk sugar) which upon hydrolysis by galactosidase (Lactase) will produce glucose and galactose. The glucose will enter the glycolysis. Galactose then will be phosphorylated to galactose-1-phosphate by the enzyme galactokinase. ATP is the P donor 3  Galactose Metabolism G  UDP-Galactose Formation Galactose-1-phosphate (can’t enter glycolytic pathway unless it is 1st converted to UDP-galactose) will transferred to UTP to produce UDP-galactose. This occurs as an exchange reaction, in which UMP is removed from UDP-glucose (leaving behind Glucose-1-Phosphate), & is then transferred to the galactose 1-Phosphate, producing UDP-galactose. 5  UDP-Galactose Formation The enzyme which catalyzes this reaction is galactose 1- phosphate uridyl transferase  This reaction will produce glucose -1-P hosphate and UDP- galactose, the former will get into glycolsis after its conversion into glucose-6-P hosphate by glucomutase. The UDP-galactose will have two fates: 1. It can be used to number of synthetic pathways to synthesis different type of glycoproteins, or lactose and others. 2. It can be epimerized into UDP-glucose by the enzyme UDP- Galactose-4-epimerase CH2 OH CH2 OH O O OH H H [NAD+ ] H H H O O OH H OH H H O P UMP UDP-Galactose- OH O P UMP 4-Epimerase O– O – H OH H OH UDP-Galactose UDP-Glucose 6 Disorder of Galactose Metabolism 7  Galactosemia  Galactosemia (Cataracts, Mental Retardation, and Death)  Primary Cause Defect in Galactose-1-Phosphate Uridyl Transferase  Mechanism Accumulation of Toxic by-Products  Treatment Galactose-free diet Galactosemia  Reversal of all symptoms except mental retardation 8  Cataracts in Galactosemia  Cataract occurs due to accumulation of galactose inside the cells  Leading to its reduction to galactitol  Which upon accumulation will induce osmotic swelling and galactosemic cataract H O C CH2OH H C OH H C OH NAD(P)H NAD(P)+ HO C H HO C H HO C H HO C H H C OH H C OH CH2OH CH2OH Galactose Galactitol 9 Summary 10 Reference Book: Champe, P. C., Harvey, R. A. and Ferrier, D. R., 2005. Biochemistry “Lippincott’s Illustrated Reviews”, 5th or 6th Edition 11