Question

Leigh syndrome is a progressive brain disease that first manifests in individuals between the ages of 6-36 months. Most patients with Leigh syndrome die at a young age. Individuals with Leigh syndrome have a defect in their mitochondrial function.

About 15% of individuals with Leigh syndrome carry mutations in their SURF1 genes.  The SURF1 gene is located on the long arm of chromosome 9 and encodes a protein that is essential for assembling one of the respiratory chain complexes, complex IV, located in the inner mitochondrial membrane.

a. Consider the following processes. Would each occur at a higher rate, lower rate or normal ratein a person with Leigh syndrome compared to a person without the syndrome? Explain briefly (4 pts)

Glycolysis

Pyruvate oxidation

Citric Acid cycle

  

ATP production by ATP synthase

b. Patients with Leigh syndrome may also suffer effects from acidosis, characterized by low pH in body tissues and blood. Why would patients with Leigh syndrome have acidosis? Explain briefly (2 pts)

c. Some metabolic disorders can be alleviated by giving the patient a specialized diet. Fats are broken down to fatty acids & glycerol in the liver, and through a process, beta-oxidation into acetyl CoA. If glucose and fat sources are depleted, amino acids can also be converted into molecules that can enter the TCA cycle. Would a low-carbohydrate, high-protein and high-fat diet help individuals with Leigh syndrome? Explain briefly. (2 pts)

Answer 1

Answer a.

Glycolysis- will occur at normal rate since this disease does not hamper any of the emzyme steps in glycolysis because it does not occur in mitochondria

Pyruvate oxidation- will occure at a slower rate because of deficient pyruvate dehydrogenase enzyme. Pyruvate will not get converted to Acetyl CoA

Citric acid cycle- will occur at slower rate due to non availability of sufficient pyruvate

Answer b. Patients with this disease have accumulation of pyruvate in their body which causes acidosis. This is due to impaired pyruvate dehydrogensa enzyme which is not able to convert pyruvate to acetyl CoA.

ANswer c. Yes, a high protein, high fat and low carbohydrate diet will help alleviate the symptoms. Fatty acids and amino acids can get into TCA cycle by converting through other processes which do not involve pyruvate dehydrogenase. Patient should be given low carbohydrate diet since they are unable to utilise glucose for energy generation.