Q.38

In ‘Futile Cycle’ chemical energy is dissipated as heat due to two opposite biochemical

reactions. Which of the following biochemical reaction(s) is/are a part of ‘Futile Cycle’?

(A) Glucose  Glucose-6-phosphate

(B) Fructose-6-phosphate  Fructose-1,6-bisphosphate

(C) Glucose-6-phosphate  Fructose-6-phosphate

(D) 1,3-bisphosphoglycerate  3-phosphoglycerate

Futile Cycle in Biochemistry: Key Reactions and Exam Insights

Futile cycles, also known as substrate cycles, occur when opposing enzymatic reactions run simultaneously, dissipating ATP as heat without net metabolic progress. In glycolysis and gluconeogenesis, specific irreversible steps form these cycles, with the correct answer being option (B) Fructose-6-phosphate ↔ Fructose-1,6-bisphosphate.

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What is a Futile Cycle?

Futile cycles involve forward and reverse reactions catalyzed by different enzymes, consuming ATP and generating heat to regulate metabolite levels. The classic example pairs phosphofructokinase-1 (PFK-1) in glycolysis with fructose-1,6-bisphosphatase (FBPase-1) in gluconeogenesis, yielding net ATP hydrolysis: ATP + H₂O → ADP + Pᵢ + heat. These cycles prevent simultaneous pathway activation, enabling precise control via allosteric regulators like fructose-2,6-bisphosphate.

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Correct Answer: Option (B)

Fructose-6-phosphate converts to fructose-1,6-bisphosphate via PFK-1 (glycolysis, ATP-dependent), while the reverse uses FBPase-1 (gluconeogenesis, hydrolytic). Simultaneous activity wastes energy as heat, exemplifying the futile cycle in carbohydrate metabolism. This pair is a textbook case due to their irreversible nature and regulatory importance.

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Analysis of All Options

• (A) Glucose ↔ Glucose-6-phosphate: This reversible reaction, catalyzed by glucokinase/hexokinase (forward) and glucose-6-phosphatase (reverse), forms another futile cycle at glycolysis/gluconeogenesis entry. It dissipates ATP but is less emphasized than PFK/FBPase in standard contexts.

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• (B) Fructose-6-phosphate ↔ Fructose-1,6-bisphosphate: Correct, as detailed above; primary futile cycle example with strong heat dissipation potential.

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• (C) Glucose-6-phosphate ↔ Fructose-6-phosphate: Catalyzed by reversible phosphoglucose isomerase; lacks opposing irreversible enzymes, so not a futile cycle.

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• (D) 1,3-bisphosphoglycerate ↔ 3-phosphoglycerate: Involves phosphoglycerate kinase (reversible ATP-related step); true futile cycle exists here with gluconeogenic bypass via phosphoglycerate mutase/bisphosphoglycerate mutase, but less canonical than (B).

  Option	Reaction Pair	Forms Futile Cycle?	Key Enzymes
  A	Glucose ↔ G6P	Yes (bypass pair)	Glucokinase, G6Pase

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  B	F6P ↔ F1,6BP	Yes (primary)	PFK-1, FBPase-1

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  C	G6P ↔ F6P	No (reversible)	Phosphoglucose isomerase

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  D	1,3BPG ↔ 3PG	Partial (bypass)	PGK, mutases

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