All of the following statements about glycolytic enzymes are true EXCEPT:

Question

Accepted Answer

D. Aldolase catalyzes the cleavage of fructose-1,6-bisphosphate into two three-carbon sugars without requiring any cofactor. ## Analysis of Glycolytic Enzyme Properties

### Correct Statements (Options 0, 1, 2)

**Key Point:** Hexokinase exhibits product inhibition by glucose-6-phosphate, a classic feedback mechanism that prevents excessive phosphorylation when G6P levels are high.

**High-Yield:** Phosphofructokinase-1 (PFK-1) is the primary rate-limiting step of glycolysis and is activated by AMP (and ADP), signaling low energy status — this is a fundamental regulatory principle.

**Key Point:** Pyruvate kinase is inhibited by both ATP (high energy signal) and acetyl-CoA (abundant biosynthetic precursor), preventing futile glucose breakdown when energy is abundant.

### The Incorrect Statement (Option 3)

**Warning:** Aldolase does NOT catalyze a simple cleavage reaction. It is a **Class I aldolase** (in animals) that requires a **Schiff base intermediate** formed between the ketone group of fructose-1,6-bisphosphate and a lysine residue in the enzyme's active site. This is a covalent catalytic mechanism, not a cofactor-independent cleavage.

**Mnemonic:** **AAAA** = **Aldolase Activates via Amino acid (Schiff base)**. The Schiff base is the critical intermediate.

### Comparison of Aldolase Mechanisms

| Feature | Class I Aldolase (Animals) | Class II Aldolase (Bacteria) |
|---------|---------------------------|------------------------------|
| Cofactor requirement | None (covalent Schiff base) | Zn²⁺ metal ion |
| Mechanism | Lysine residue forms imine | Metal coordinates substrate |
| Intermediate | Schiff base (carbinoamine) | Zn-enamine |

**Clinical Pearl:** Deficiency of aldolase B (fructose-1-phosphate aldolase) causes hereditary fructose intolerance, not a glycolysis defect per se, but demonstrates the physiologic importance of this enzyme family.

[cite:Lehninger Principles of Biochemistry 8e Ch 14]

Answer

A. Hexokinase is inhibited by its product glucose-6-phosphate

Answer

B. Phosphofructokinase-1 is the rate-limiting enzyme of glycolysis and is activated by AMP

Answer

C. Pyruvate kinase is a regulatory enzyme that is inhibited by acetyl-CoA and ATP

All of the following statements about glycolytic enzymes are true EXCEPT:

Explanation

Analysis of Glycolytic Enzyme Properties

Correct Statements (Options 0, 1, 2)

The Incorrect Statement (Option 3)

Comparison of Aldolase Mechanisms

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Feature	Class I Aldolase (Animals)	Class II Aldolase (Bacteria)
Cofactor requirement	None (covalent Schiff base)	Zn²⁺ metal ion
Mechanism	Lysine residue forms imine	Metal coordinates substrate
Intermediate	Schiff base (carbinoamine)	Zn-enamine