Biosc

1000

Sample Problems Lecture 15

1. Why is it advantageous to have the synthesis and the degradation of glycogen
controlled by different enzymes?

Because glycogen synthetic and degradative pathways both occur in the
cytoplasm, having these processes controlled by different enzymes prevents a
useless cycle of breaking down newly made glycogen. To prevent this futile
cycling, the rate limiting enzymes in each pathway are controlled allosterically
and coordinately. Thus, allosteric modulators that activate glycogen
phosphorylase and inactivate glycogen synthase allowing metabolic flux to
proceed in one direction.

2. Glycogen catabolism releases glucose-1-phosphate, the substrate used by the
first enzyme in the synthetic pathway; what prevents a futile cycling of
glucose into and out of glycogen?

In order for the glucose-1-phosphate to be re-made into glucogen, it must be
converted into UDP-glucose by a reaction that is coupled to glycogen synthase. If
glycogen synthase activity is reduced then the necessary release and hydrolysis of
pyrophosphate is also decreased, effectively preventing the synthetic reactions.

3. Which condition, a muscle phosphorylase deficiency or a muscle glycogen
synthase activity deficiency, do you think would easier to treat?

A glycogen synthase deficiency because the glucose that enters muscle does not
become trapped as glycogen and could be used by the tissue or
dephosphorylated and released back into circulation. Dietary control would be
much simpler because the issue is making sure enough glucose is present in
circulation. A phosphorylase activity defect would allow gluocse to accumulate
in muscle and liver as glycogen without an easy way to make in available.

4. Allosteric modulators act by binding to the enzyme whereas covalent
modification (phosphorylation) is catalytic process which do you think
provides a more rapid change in metabolic flux?

Covalent modification, because once an enzyme becomes phosphorylated (and
activated for example) will maintain that level of activity until the phosphate
is removed. An allosteric modulator can easily diffuse out of its binding site on
the enzyme, so its activation of inhibition tends to be more transient.
Furthermore, changes to enzyme activity through phophorylation are
enzymatic processes, so many enzymes can be activated as a result of a single
signal. This accounts for the rapidity of the process, one activated enzyme can
produce hundreds of enzymes producing thousands of products whereas one
allowsteric modulator can only affect one enzyme as it produces its product.

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