Deficiency of which enzyme results in increased 2,3-BPG levels and low glucose values in vitro?

AIIMS Delhi NO - 2017

Biochemistry & Nutrition

Hard

Appeared in: AIIMS Delhi NO - 2017

Explanation

Pyruvate kinase (PK) is the final enzyme in the glycolytic pathway in red blood cells, responsible for converting phosphoenolpyruvate to pyruvate while generating ATP.
A deficiency in PK causes a metabolic block, leading to the accumulation of upstream intermediates.
This backup results in increased levels of 2,3-bisphosphoglycerate (2,3-BPG), a molecule that helps release oxygen from hemoglobin to the tissues.
The inefficient ATP production in PK deficient cells can lead to increased glucose consumption as a compensatory mechanism, resulting in low glucose levels in stored blood samples (in vitro).

Option B: While a deficiency in phosphoglycerate kinase (PGK), an enzyme upstream of PK, can also lead to increased 2,3-BPG, it is a much rarer condition. Pyruvate kinase deficiency is the classic and more common cause of this specific metabolic profile.
Option C: Glucose-6-phosphate dehydrogenase (G6PD) is part of the hexose monophosphate (HMP) shunt, not the main glycolytic pathway. Its deficiency impairs the cell's ability to handle oxidative stress and does not directly cause accumulation of 2,3-BPG.
Option D: Hexokinase is the first enzyme in the glycolytic pathway. A deficiency at this initial step would prevent glucose from entering the pathway effectively, leading to decreased levels of all downstream intermediates, including 2,3-BPG.

Clinical Relevance

Nursing practice connection: Knowing Red blood cell metabolism and glycolytic enzyme deficiencies helps nurses interpret findings accurately and avoid errors in routine assessment, medication administration, and patient teaching.
Pyruvate kinase deficiency is the most common cause of congenital nonspherocytic hemolytic anemia.
The increased 2,3-BPG levels are a key compensatory mechanism. By shifting the oxygen-hemoglobin dissociation curve to the right, it enhances oxygen delivery to tissues, which is why patients often tolerate the anemia better than expected for their hemoglobin level.
Diagnosis involves measuring the enzyme activity in red blood cells. It's important for nurses to know that a blood sample for this test should be handled correctly, as factors like reticulocyte count can affect the results.

How to Approach the Question

First, identify the core concepts in the question: an enzyme deficiency affecting 2,3-BPG and glucose levels in red blood cells.
Recall the glycolytic pathway, the primary energy source for red blood cells. Visualize the sequence of enzymes.
Analyze the effect of a block at different points in the pathway. A block late in the pathway (like Pyruvate Kinase) will cause upstream products to accumulate.
Evaluate each option: Hexokinase is at the start, G6PD is in a different pathway, and both Phosphoglycerate Kinase and Pyruvate Kinase are in the latter half of glycolysis.
Deduce that a block at the end (Pyruvate Kinase) is the most logical cause for the accumulation of an upstream product like 2,3-BPG.
Connect the inefficient ATP production to increased glucose consumption to understand the 'low glucose in vitro' part of the question.

Concept Tested & Keywords

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