Case 1:
Pyruvate Kinase (PK) catalyzes the rate-limiting, ATP-generating step of glycolysis in
which phosphoenolpyruvate (PEP) is converted to pyruvate. Multiple isoenzymes of
pyruvate kinase exist in mammals: type L, which is found in the liver and kidneys; type
R, which is expressed in erythrocytes; type M1, which is found in tissues such as muscle
and brain; and type M2, which is present in self renewing cells such as embryonic and
adult stem cells.
1. Under normal conditions, describe all the waysin which pyruvate kinase isregulated
in the cell?
Many types of cancer cells are predominantly glycolytic and over express the
oncoprotein MYC. Interestingly, the classical oncoprotein MYC has been found to
promote preferential expression of pyruvate kinase type M2 over pyruvate kinase
type M1.
The isoform M2 is characteristically found in a low activity state and is ineffective at
promoting glycolysis (When compared to pyruvate kinase type L or type M1).
2. Thislogic seems counter intuitive for a glycolytic tissue. What isthe rationale for this
mechanism and what other pathways may cancer cells be diverting substrate to?
Case 2:
A 16-year-old female is recently diagnosed with a deficiency of muscle glycogen
phosphorylase. She and her family are concerned and ask the following questions.
Based on what you know about skeletal muscle glycogenolysis and muscle metabolism,
please respond to each question with a thoughtful answer that describes the
metabolism in these various scenarios in language that your patient will understand,
while also being sure to include the role of the relevant metabolic pathways, specific
enzymes, and stimulus for their activity:
1. I’m notsure I understand the issue. Can you explain how muscle glycogen is used
normally during exercise?
2. I really like to take long walks; will Istill be able to do this with my friends?
3. As a result of this deficiency, will I need to get up at night to eat to maintain my blood
glucose levels?
4. Do I need to worry about producing excessive lactate during intense anaerobic
exercise?
