Q.3 Which of the following enzyme is inhibited by citrate in Kreb’s cycle?
I. Phospho-fructo kinase II (PFKII)
2. Aldolase
3. Pynrcate kinase
4. Phosphoglycerate mutase (PGM)
Correct Answer: 1 (Phospho-fructo kinase II (PFKII))
Citrate, an early intermediate in the Krebs cycle (also called the TCA or citric acid cycle), acts as a feedback inhibitor to regulate energy metabolism. It signals high energy status and inhibits key glycolytic enzymes outside the Krebs cycle to prevent unnecessary glucose breakdown. This question tests understanding of citrate’s allosteric regulation linking the Krebs cycle to glycolysis.
Option Analysis
Phospho-fructo kinase II (PFKII)
PFKII (also called PFK-2) synthesizes fructose-2,6-bisphosphate (F2,6BP), a potent activator of PFK1 in glycolysis. Citrate directly inhibits PFKII, reducing F2,6BP levels and slowing glycolysis when Krebs cycle intermediates accumulate, indicating ample energy. This is the precise match for citrate inhibition relevant to Krebs cycle regulation.
Aldolase
Aldolase cleaves fructose-1,6-bisphosphate into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate during glycolysis. It lacks allosteric sites for citrate and is not regulated by Krebs cycle intermediates like citrate.
Pyruvate Kinase
Pyruvate kinase catalyzes the final glycolysis step, converting phosphoenolpyruvate to pyruvate. It is allosterically inhibited by ATP but not directly by citrate; indirect effects via reduced F2,6BP occur, but citrate does not bind it.
Phosphoglycerate Mutase (PGM)
PGM interconverts 3-phosphoglycerate and 2-phosphoglycerate in glycolysis. It operates via a phosphohistidine mechanism without known citrate inhibition.
The enzyme inhibited by citrate in Krebs cycle regulation is a key concept in biochemistry, especially for competitive exams like GATE Life Sciences. Citrate, the first product of the Krebs cycle (TCA cycle), acts as an allosteric inhibitor to fine-tune cellular energy balance. This article breaks down the MCQ options, explains the mechanism, and highlights why Phospho-fructo kinase II (PFKII) is the correct choice.
Understanding Citrate’s Role
In the Krebs cycle, citrate forms when acetyl-CoA condenses with oxaloacetate via citrate synthase. High citrate levels signal abundant energy (high NADH/ATP), triggering feedback inhibition on upstream pathways like glycolysis. This prevents overload and diverts resources to storage or biosynthesis.
Why PFKII is Inhibited by Citrate
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PFKII Function: PFKII produces fructose-2,6-bisphosphate (F2,6BP), which allosterically activates PFK1—the rate-limiting glycolysis enzyme.
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Inhibition Mechanism: Citrate binds PFKII, reducing F2,6BP synthesis. This deactivates PFK1, slowing glycolysis and linking Krebs cycle status to glucose flux.
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Biological Relevance: Essential for fed-state regulation; high citrate from active Krebs cycle curbs glycolysis to favor fat synthesis.
Visual Aid: Imagine citrate as a “brake pedal” on glycolysis—pressing it via PFKII stops unnecessary sugar breakdown when the cell’s “energy tank” (Krebs intermediates) is full.
Why Other Enzymes Fail
| Enzyme | Role in Glycolysis | Citrate Inhibition? | Reason |
|---|---|---|---|
| Aldolase | Splits F-1,6-BP to trioses | No | No allosteric site for citrate. |
| Pyruvate Kinase | PEP to pyruvate (final step) | Indirect/No | Inhibited by ATP; citrate affects via F2,6BP drop. |
| Phosphoglycerate Mutase | 3-PG to 2-PG | No | Phosphotransfer enzyme, unregulated by citrate. |
| PFKII (Correct) | Makes F2,6BP activator | Yes | Direct allosteric inhibition. |
This table clarifies misconceptions—only PFKII fits perfectly.
Exam Tips for GATE Life Sciences
Focus on regulatory enzymes: Citrate inhibits PFK1/PFK2 (glycolysis), PDH, and isocitrate dehydrogenase (Krebs). Practice PYQs linking cycles for scoring in Biochemistry section.
