Case Study 1 Carbohydrate Metabolism

You are a doctor specializing in disorders of metabolic enzymes. An 18-year-old man

has been referred to you. He is experiencing muscular pain and tightness during
physical exertion, especially in the cold. This was making it difficult for him to do
activities of daily life and to stay employed. He also suffers from muscular cramps in
his legs when hes at rest. He has previously been diagnosed with hemolytic
anemia. Urine tests are negative and he has not noticed any changes in urine color.
You perform an ischemic exercise test, having him contract the muscle of the
forearm while restricting blood flow with a blood pressure cuff. You take blood
samples following the exercise every 30 seconds for 5 minutes. The results of this
test show normal hemoglobin and blood glucose levels, but decreased levels of
blood lactate when compared to a healthy adult performing the same test. A muscle
biopsy shows normal levels of muscle glycogen and glucose. However, it shows
levels of glucose-6 phosphate that are much lower than normal. Diagnose him with
a deficiency of a metabolic enzyme.
1. What is hemolytic anemia and what are some possible causes?
Hemolytic anemia is the breakdown of red blood cells before their normal life
span. This disease can be inherited or acquired. Possible causes include sickle
cell anemia, thalassemias, hereditary spherocytosis, glucose-6-phosphate
dehydrogenase deficiency, pyruvate kinase deficiency, immune or
autoimmune hemolytic anemia.
2. What type(s) of carbohydrate metabolism occur(s) in red blood cells?
Anaerobic glycolysis is the sole carbohydrate metabolism in erythrocytes.
3. Is this patient experiencing a disorder affecting anaerobic or aerobic
metabolism?
The patient is experiencing a disorder affecting anaerobic metabolism.
4. You decide to perform assays to check the activity of one or more
metabolic enzymes in the red blood cells. Which enzyme(s) would
you check, and why?
I would check the enzymes of glycolysis because the citric acid cycle,
electron transport chain, and oxidative phosphorylation do not occur under
anaerobic metabolism and therefore their enzymes would have no effect on
red blood cells.
5. Based on your knowledge of metabolic pathways and intermediates,
what enzyme is most likely involved in this patients disorder?
Hexokinase
6. What is the role of this enzyme in carbohydrate metabolism?
Hexokinase phosphorylates glucose to glucose-6-phosphate in the skeletal
muscle tissues.

7. Would you expect the liver to be able to metabolize carbohydrate

normally? Muscle? Why or why not?
The liver would be able to metabolize carbohydrate because it uses the
enzyme glucokinase to metabolize carbohydrates. The muscle would not be
able to metabolize carbohydrates because it uses hexokinase to metabolize
glucose to glucose-6-phosphate. This is the first reaction in glycolysis and
needs to occur in the Cori Cycle for anaerobic energy.