Glycolysis is a fundamental metabolic pathway that breaks down glucose into pyruvate, generating energy in the form of ATP. Despite being extensively studied, several misconceptions about its regulation and function persist. This article examines four statements related to glycolysis, identifies which are incorrect, and explains the biochemical principles behind them.

The Statements Under Review

A. Glycolysis is not regulated by pyruvate kinase.
B. Lactate can be an end product of glycolysis.
C. Glycolysis cannot function anaerobically.
D. In erythrocytes, the second site in glycolysis for ATP generation can be bypassed.

Our goal is to determine which combination of these statements is incorrect.

Statement A: Glycolysis Is Not Regulated by Pyruvate Kinase

This statement is incorrect. Pyruvate kinase catalyzes the final and irreversible step of glycolysis, converting phosphoenolpyruvate (PEP) to pyruvate while producing ATP. It is a key regulatory enzyme subject to allosteric control.

• Allosteric Regulation: Pyruvate kinase activity is enhanced by fructose-1,6-bisphosphate (FBP), a glycolytic intermediate, which acts as a feedforward activator. It is inhibited by ATP and alanine, signaling sufficient energy or building blocks.

• Hormonal Regulation: In the liver, pyruvate kinase is regulated by phosphorylation in response to hormonal signals like glucagon, adjusting glycolytic flux according to metabolic needs.

Thus, pyruvate kinase plays a crucial role in controlling glycolysis, contradicting statement A.

Statement B: Lactate Can Be an End Product of Glycolysis

This statement is correct. Under anaerobic or low oxygen conditions, such as in muscle cells during intense exercise or in erythrocytes, pyruvate is reduced to lactate by lactate dehydrogenase. This reaction regenerates NAD+, allowing glycolysis to continue producing ATP without oxygen.

Lactate accumulation is a well-known physiological response to anaerobic metabolism, confirming the validity of statement B.

Statement C: Glycolysis Cannot Function Anaerobically

This statement is incorrect. Glycolysis is the primary pathway for ATP production under anaerobic conditions. It does not require oxygen and can proceed as long as NAD+ is regenerated, typically through lactate or ethanol fermentation depending on the organism.

Thus, glycolysis functions efficiently in the absence of oxygen, disproving statement C.

Statement D: In Erythrocytes, the Second Site in Glycolysis for ATP Generation Can Be Bypassed

This statement is correct. Erythrocytes possess a unique metabolic adaptation known as the Rapoport-Luebering shunt, which involves the enzyme bisphosphoglycerate mutase.

• This shunt diverts 1,3-bisphosphoglycerate to 2,3-bisphosphoglycerate (2,3-BPG), bypassing the ATP-generating step catalyzed by phosphoglycerate kinase.

• The bypass allows regulation of oxygen release from hemoglobin without compromising the entire glycolytic flux.

Therefore, statement D is accurate.

Summary of Correctness

Identifying the Combination of Incorrect Statements

The incorrect statements are A and C.

Given the options:

1. A and B

2. B and D

3. C and D

4. A, C and E (E is not provided, likely a typographical error)

Since option (4) includes A and C, it best fits the requirement of containing both incorrect statements.

Conclusion

The statements A (glycolysis is not regulated by pyruvate kinase) and C (glycolysis cannot function anaerobically) are both incorrect. Pyruvate kinase is a key regulatory enzyme in glycolysis, and glycolysis can function anaerobically by regenerating NAD+ through lactate formation.

Correct answer: (4) A, C and E (assuming E is a typographical error or extraneous)