HW Lecture #22: Glycogen Metabolism

Pg. 464 (Study Exercises 1, 2, 5) see back of book for answer to Problems 9 and 10 and explanation for #10 below:

1. Metabolic sources of G6P: Glucose (via hexokinase); glycogen (via glycogen phosphorylase and phosphoglucomutase). Metabolic products of G6P are pyruvate (via glycolysis), ribose-5-phosphate (via pentose phosphate pathway) and glucose (via glucose-6-phosphatase found only in the liver).
2. The structure of glycogen (highly branched glucose residues linked by alpha (1-4) glycosidic linkages relates to function because; i. The alpha (1-4) glycosidic linkages cause the molecule to coil, which makes it pack well and makes it more water soluble); ii. Branches provide many free non-reducing ends for glycogen phophorylase to cleave glucose residues and rapidly mobilize glucose molecules; iii. Storing glucose as big molecules of glycogen, rather than many small molecules of glucose decreases total osmotic pressure. If glucose were stored as individual molecules you would need to carry a lot more water with it to balance the osmotic pressure.

5. A phosphorylation/dephosphorylation system allows for more sensitive regulation of a metabolic process than a simple allosteric system because ii. phosphorylation can be regulated by signalling molecules such as hormones and neurotransmitters and ii. Phosphorylation allows for amplication if one phosphorylated molecule phosphorylates 3 molecules, which then phosphorylates 3 more molecules etc.

AND

10). A sample of glycogen from a patient with liver disease is incubated with Pi, normal glycogen phosphorylase, and normal debranching enzyme. The ratio of G1P to glucose formed in this reaction mixture is 100 (where 10 is normal). What is the patients most probable enzymatic deficiency?

The book (and many students’ answers) read: "The deficiency is in branching enzyme (Type IV glycogen storage disease). The high ratio of G1P to glucose indicates abnormally long chains of alpha (1-4) linked residues with few alpha (1-6) linked branch points (the normal ratio is 10).

Does this make sense? A good explanation is as follows:

Glycogen phosphorylase releases a glucose unit only if it is at least 5 units away from a branch point.

Glycogen (n units) + Pi à Glycogen (n-1 units) + G1P

The high ratio of G1P/glucose suggests that the main chain of glycogen has few branches. This means it can be "phosphorylysed" readily (generating lots of G1P), without having to wait around for the debranching enzyme to do its job. A deficiency in branching enzyme results in long unbranched chains. So, a high G1P/glucose ratio is consistent with a deficiency in branching enzyme. Interestingly liver dysfunction resulting from this disease may be caused by a "foreign body" immune reaction to the abnormal glycogen. Victims rarely survive past the age of 4 years because of liver dysfunction (pg. 448).