Question

A man is given antibiotics to treat a urinary tract infection and develops an episode of red blood cell lysis. Further studies show weakness of the plasma membrane and Heinz bodies (collections of oxidized hemoglobin). Which of the following enzymes is most likely defective in this patient? (A) Fructose-1,6-bisphosphatase (B) Glucose-6-phosphate dehydrogenase (C) Hexokinase (D) Pyruvate kinase

Short answer

B) Glucose-6-phosphate dehydrogenase

Step-by-step solution

Identify Symptoms

The patient developed red blood cell lysis, showing weakness in the plasma membrane and Heinz bodies.

Link Symptoms to Biochemical Pathways

Heinz bodies are formed due to oxidized hemoglobin, indicating an issue with maintaining redox balance within red blood cells.

Determine Enzyme Role

Among the given options, glucose-6-phosphate dehydrogenase (G6PD) plays a crucial role in the pentose phosphate pathway, which maintains the redox state in red blood cells by producing NADPH. NADPH is necessary to prevent oxidative damage.

Identify the Correct Enzyme Defect

A defect in G6PD leads to reduced NADPH production, making red blood cells more susceptible to oxidative damage and subsequently forming Heinz bodies.

Key concepts

Red Blood Cell Lysis

Red blood cell lysis means the breaking down of red blood cells. This causes the release of hemoglobin into the blood. This process can be triggered by various factors, including infections, medications, and inherited conditions. Key signs of red blood cell lysis include fatigue, shortness of breath, and anemia. It's crucial to understand that red blood cell lysis disrupts oxygen transport in the body.

When red blood cells break down too quickly, the body can't produce new cells fast enough to replace them. This leads to symptoms like paleness and jaundice. Continuous breakdown can also cause serious complications like kidney damage and heart problems.

Heinz Bodies

Heinz bodies are clumps of damaged hemoglobin found inside red blood cells. They form when hemoglobin is exposed to oxidative stress, making it denature and precipitate. These bodies appear as small dark spots when viewed under a microscope. The presence of Heinz bodies is a key indicator of oxidative stress within red blood cells.

Conditions like G6PD deficiency and certain medications can lead to the formation of Heinz bodies. They compromise the integrity of red blood cells, making them more prone to lysis. In a lab test, identifying Heinz bodies can help diagnose various underlying health issues related to red blood cell damage.

NADPH

NADPH, which stands for nicotinamide adenine dinucleotide phosphate, is a crucial molecule in protecting cells from oxidative damage. It acts as a reducing agent, helping to maintain the balance of antioxidants in the body. In red blood cells, NADPH is necessary for the production of glutathione, an important antioxidant.

Without adequate NADPH, cells cannot defend against oxidative stress, leading to damage and cell death. In the context of G6PD deficiency, the lack of NADPH means that red blood cells are especially vulnerable to oxidative damage, resulting in symptoms like red blood cell lysis and the presence of Heinz bodies.

Pentose Phosphate Pathway

The pentose phosphate pathway (PPP) is a metabolic pathway parallel to glycolysis. It mainly serves to generate NADPH and ribose-5-phosphate, which are essential for cellular processes. The PPP is crucial in red blood cells since these cells rely on it to produce NADPH.

In the context of G6PD deficiency, the inability to produce sufficient NADPH via the PPP makes red blood cells more susceptible to oxidative stress. The PPP is not just limited to red blood cells; it is active in all cells and critical for the synthesis of nucleotides and nucleic acids.

Oxidative Damage

Oxidative damage occurs when there is an imbalance between the production of free radicals and the body's ability to neutralize them with antioxidants. Free radicals are molecules with unpaired electrons, making them highly reactive. They can damage cells, proteins, and DNA, leading to various diseases.

In the context of red blood cells, oxidative damage can weaken the cell membrane and lead to conditions like red blood cell lysis. The body usually uses antioxidants like glutathione to counteract oxidative damage, but this process depends on NADPH. In G6PD deficiency, the reduced production of NADPH hampers the ability to neutralize oxidative stress, resulting in increased cell damage and the formation of Heinz bodies.