1.

Patients with von Gierke's disease (type I glycogen storage disease) have a deficiency of glucose-
6-phosphatase. One of the most prominent symptoms of the disease is a protruding abdomen
due to an enlarged liver. Explain why the liver is enlarged in patients with von Gierke's disease.

Hepatomegaly, or having an enlarged liver is common in patients with von gierke’s

disease due to fat and glycogen deposition in the liver. This accumulation of glycogen and fat in
the liver is caused by the deficiency of the enzyme G6Pase or G6PT (Glucose-6-Phosphate
Translocase). G6PT is responsible for the translocation of G6P from the cytoplasm into the ER
lumen. The G6Pase-G6PT complex must catalyze the final step of glycogenolysis and
gluconeogenesis in order to produce glucose.

2. During even mild exertion, individuals with McArdle’s disease experience painful muscle cramps
due to a genetic defect in glycogen phosphorylase, the enzyme that breaks down glycogen. Yet
the muscles in these individuals contain normal amounts of glycogen. What did this observation
tell researchers about the pathways for glycogen degradation and glycogen synthesis?

For patients with McArdle disease, basically their muscles cannot make use of the
energy in the body. For a normal muscle to work well, it must have a constant supply of glucose.
Glucose is stored in a form of energy storage called glycogen, and normally, the body can break
down glycogen so that glucose can be used (steady supply), Researchers found out that people
with McArdle’s Disease is missing an enzyme called myophosphorylase, which is an enzyme that
breaks down glycogen, it is one of the glycogen phosphorylases that breaks down glycogen and
it is specific to muscle cells where it breaks down glycogen into glucose-1-phosphate.

3. Cancer cells have elevated levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH),

which may account for the high rate of glycolysis seen in cancer cells. The compound
methylglyoxal has been shown to inhibit GAPDH in cancer cells but not in normal cells. This
observation may lead to the development of rapid screening assays for cancer cells and to the
development of drugs for treatment of cancerous tumors.
a. What mechanisms might be responsible for the elevated levels of GAPDH in cancer cells?
b. Why might methylglyoxal inhibit GAPDH in cancer cells but not in normal cells?

a. GAPDH was initially known to be a housekeeping gene and a glycolytic enzyme. As a

glycolytic enzyme, GADPH participates in cancer cell proliferation because cancer
cells uses aerobic glycolysis as their main metabolic pathway in relation with cell
proliferation.
b. Methylglyoxal is one of the most powerful glycating agents as it is extremely
reactive especially with compounds that are present in cancer cells with
upregulated GADPH such as in hypoxia or CICD. It does not interact with normal
cells that have normal pathways.
4. A patient seeks treatment because her metabolic rate is twice normal and her temperature is
elevated. A biopsy revealed that her muscle mitochondria are structurally unusual and not
subject to normal respiratory controls. Electron transport takes place regardless of the
concentration of ADP.
a. What is the P:O ratio (compared to normal) of NADH that enters the electron transport chain
in the mitochondria of this patient?
b. Why are the patient’s metabolic rate and temperature elevated?
c. Will the patient be able to carry out strenuous exercise?

a. For every two electrons that go through a substrate, there is ATP. The P:O ratio
describes the number of phosphates that is affixed to the ATP every cycle. Using
NADH as the electron donor, then the P:O would be 2:3. If the metabolic rate of the
patient is twice than normal, the P:O would probably increase too.
b. For a person to generate energy and maintain the body temperature, the source of
the energy (mitochondria) has to generate more heat endothermically and they
operate at a temperature higher than normal. A person with an abnormal muscle
mitochondria would naturally have an increased metabolic rate, and it can be
expected that with an increase metabolic rate, the body temperature would also
increase.
c. It would be difficult and strenuous for the patient to perform strenuous exercise as
it will require the production of energy and increased activity in the mitochondria,
increasing the temperature of the patient more than normal.
5. The standard free energy change (ΔG°’) for hydrolysis of phosphoenolpyruvate is -61.9 kJ/mol.
The standard free energy change (ΔG°’) for ATP hydrolysis is -30.5kJ/mol.
a. What is the standard free energy change for the pyruvate kinase reaction: ADP +
phosphoenolpyruvate → ATP + pyruvate
b. What is the equilibrium constant for this reaction?
c. Assuming the intracellular concentrations of [ATP] and [ADP] remain fixed at 8mM and 1mM,
respectively, what will be the ratio of [pyruvate]/[phosphoenolpyruvate] when the pyruvate
kinase reaction reaches equilibrium?

a. ADP+phospoenolpyruvate->ATP+pyruvate
deltaG= -61.9+31.5
deltaG=-31.4 kj/mol
b. deltaG=-RTlnK
-31400=-(8.314)(298)lnK
K=e^(-31400/(8.314)(298))
K=3.19x10^5
[ ATP ] { pyruvate ] [ 8 ] { pyruvate ]
c. K= = =3.19 x 105
{ adp } { PEP } { 1 } { PEP }
Pyruvate/pep=39,875