Question

You demonstrate that fluoride ion inhibits the conversion of 2-phosphoglycerate to phosphoenolpyruvate and that elevated levels of fluoride ion completely abolished glycolysis in the cultured normal liver cells. However, you still detected 14CO2 production when the normal liver cells were incubated with 14C-1 labeled glucose. You also test cultured liver cells obtained from a South African patient who suffers from jaundice (a yellow discoloration of skin and sclera due to too much bilirubin), kidney failure, hemoglobinuria (aggregation of oxidized hemoglobin), and hemolysis. The patient's liver cells produce 14C-3 labeled pyruvate and 14CO2 when incubated with 14C-1 labeled glucose in the absence of fluoride ion. However, radiolabeled 14CO2 was not produced when the same cells were incubated with 14C-1 labeled glucose in the presence of high levels of fluoride ion. Explain the metabolic basis for the results from both types of cultured hepatocytes

Answer 1

ANSWER :-

1. Fluoride is considered as a potential inhibitor of the enzyme Enolase. Enolase is the enzyme involved in Glycolysis which helps in the conversion of the substrate 2-Phosphoglycerate to Phosphoenolpyruvate. The enzyme is associated by co-factors like Magnesium ion.
2. At the second carbon position, the substrate 2-Phosphoglycerate shows presence of phosphate ion which is supported by the activity of Magnesium ion which helps to bring about confirmational changes as well as catalysis reaction.
3. Two magnesium ions are involved in which one is associated with bringing about confirmational changes in the enzyme structure and the second one attached to the Enzyme-substrate complex and hence is called as the catalytic factor associated with the enzyme activity.
4. Fluoride ion plays an important role in forming a link between the incoming magnesium ion and the Phosphate ion of the substrate which inhibits binding of magnesium and thus inhibits the enzyme activity of Enolase. Hence, this is the reason why radiolabelled CO2 production was not associated as simultaneous steps did not happen with respect to production of pyruvate and hence carbon dioxide output was not considered.

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