A liver sample from a rat starved for 48 hours was used to produce a culture of

Question

A liver sample from a rat starved for 48 hours was used to produce a culture of liver cells (hepatocytes). The hepatocytes were grown in the presence of the fatty acid oleate at 0.05 mmol/liter. Under these culture conditions, the concentration of intramitochondrial oxaloacetate is 5 mole/liter. When the concentration of oleate is raised to 0.5 mmol/liter the concentration of mitochondrial oxaloacetate drops to 2 mole/liter.

1) Explain this observation.
Hint: In the citric acid cycle, Acetyl-CoA react with oxaloacetate, and oxaloacetate is produced by the reversible reaction: malate + NAD+ oxaloacetate + NADH + H+

2) What is the consequence of this decrease of the concentration of mitochondrial oxaloacetate on the citric acid cycle and on the fate of acetyl-CoA?

3) Do you expect any change in the concentration of cytosolic oxaloacetate? Explain

Explanation / Answer

1. After starvation we are adding oleate it used has a energy source to the cells. It undergo oxidation and release lot of Acetyl CoA. This acetyl coA used in citric acid cycle to produce a lot of energy in mitochondria. Increase in oleate conc. increases the acetyl coA so lot of acetyl coA available to react with mitochondrial oxaloacetate to convert into citrate. So there is a decrease in conc. of mitochondrial oxaloacetate.

2. If continuous decrease in mitochondrial oxaloacetate leads to inhibition of citric acid cycle or decrease the ATP synthesis and accumulation of oxaloacetate in the cells.

3. The cytosolic oxaloacetate enter in to mitochondria and used in citric acid cycle. So concentration of cytosolic oxaloacetate would be decrease.

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