Lecture 38 Flashcards
What is the structure of glycogen composed of?
1) Glycogen is a polysaccharide in which glucosyl residues are joined by glycosidic links
2) The major linkage between glucosyl residues are alpha 1 -> 4 with branch points in the chain that are alpha 1 -> 6 and occur at an average spacing of 8 to 12 alpha 1 -> 4 links
What is the function of glycogen and where does it function?
1) Glycogen serves as a storage form of carbohydrate
2) In a well fed individual the concentration per gram tissue is highest in the liver, but the glycogen in liver can be depleted by a 24 hour fast
3) Glycogen is less readily depleted in muscle and there is more total glycogen in muscle than in any other tissue of the body
4) Brain has a very low glycogen concentration. The brain is largely dependent upon circulating glucose for the carbohydrate that it requires
How is glycogen synthesized?
1) Glucose-6-phosphate is converted to Glucose 1-phosphate in a reversible reaction catalyzed by phosphoglucomutase
2) Glucose 1-phosphate + UTP (uridylyltransferase) –> UDP-glucose + pyrophosphate catalyzed by UDP-glucose pyrophosphorylase
3) Glycogen synthase catalyzes the transfer of glucose from UDP-glucose to glycogen with the formation of an alpha 1 –> 4 link
4) Branch points are formed by glycogen branching enzyme (amylo 1-4 –> 1-6 transglucosylase)
How is glycogen broken down?
1) Alpha 1 –> 4 links in glycogen are broken by a phosphorolytic cleavage that requires inorganic phosphate and produces glucose 1-phosphate. The reaction is catalyzed by the enzyme glycogen phosphorylase
2) Branch points are cleaved by a hydrolytic reaction that produces free glucose and is catalyzed by glycogen debranching enzyme. This enzyme also has a transferase activity that can transfer a small oligosaccharide near a branch point to a longer alpha 1 -> 4 linked chain
What is lactose?
Lactose is a disaccharide consisting of galactose and glucose with a beta 1-4 glycosidic linkage
Can lactose be absorbed from the intestinal tract?
No
How can lactose be digested?
Digestion of lactose requires the hydrolysis of lactose to galactose and glucose catalyzed by the enzyme lactase
What causes lactose intolerance?
Insufficient lactase activity causes lactose intolerance in which intestinal bacteria metabolize lactose to acids and carbon dioxide (acids and carbon dioxide can cause intestinal disturbances/irritability)
What is the function of galactokinase?
It phosphorylates galactose in the 1C position to form Galactose 1-phosphate
What occurs in galactokinase deficiency?
1) This causes galactosemia and galactosuria
2) This also causes galactitol accumulation if galactose is present in the diet
What are characteristics of classic galactosemia?
1) Uridyltransferase deficiency
2) Autosomal recessive disorder
3) It causes galactosemia and galactosuria, vomiting, diarrhea, & jaundice
4) Accumulation of galactose 1-phosphate and galactitol in nerve, lens, liver, & kidney tissue causes liver damage, severe mental retardation, & cataracts
5) Antenatal diagnosis is possible by chorionic villus sampling
6) Therapy: Rapid diagnosis and removal of galactose (therefore, lactose) from the diet
Where does aldose reductase function?
The enzyme is present in the liver, kidney, retina, lens, nerve tissue, seminal vesicles, & ovaries
What does aldose reductase do?
Aldose reductase converts galactose to galactitol by oxidizing NADPH –> NADP+
Is aldose reductase physiologically important?
It is physiologically unimportant in galactose metabolism unless galactose levels are high (as in galactosemia)
What can elevated levels of galactitol cause?
Elevated levels of galactitol can cause cataracts
