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Before even telling you what G6PD is or why it’s significant, you need to know this:
| A USMLE question writer’s obsession: G6PD deficiency is X-linked recessive. |
Ok cool. Now that that’s out of the way, the reason the USMLE gives a fuck about G6PD is because it’s used to generate NADPH.
Why is NADPH important? Because it’s production ultimately leads to the mopping up of free radicals and the neutralizing of oxidizing agents and H2O2.
| Presence of G6PD → means NADPH production → ↑ protection against oxidizing agents + H2O2 |
Adding an extra piece of info, NADPH helps convert oxidized glutathione into reduced glutathione. The latter is a reducing agent that neutralizes oxidizing agents.
| Oxidizing agents = damage DNA = bad
Reducing agents = neutralize oxidizing agents → therefore good Presence of G6PD → production of NADPH → more reduced glutathione → more (H2O2 → H2O) |
In turn, G6PD deficiency can lead to hemolysis secondary to oxidative stress.
| Sulfa drugs (e.g., furosemide, sulfonamides, sulfonylureas) are notorious for causing hemolysis in G6PD. |
Questions classically mention an African-American boy with decreased hematocrit after receiving a drug (e.g., dapsone, primaquine, sulfonamides).
But hemolysis can also occur with consumption of fava beans (favism).
| Questions also love to you to know bite cells and Heinz bodies are characteristic of G6PD deficiency.
Heinz bodies = denatured/oxidized hemoglobin inside RBCs Bite cells (degmacytes) = RBCs with tiny, semicircular pieces missing that are formed when the spleen removes the Heinz body but allows the rest of the RBC to remain in the circulation. These RBCs nevertheless have decreased lifespan. |
The reduced lifespan of a bite cell RBC = ↑ RBC turnover = ↑ resistance to malaria.
| G6PD deficiency and sickle cell trait/disease both confer resistance to malaria because shorted RBC lifespan → impedance of malaria lifecycle |
The last factoid:
| Two most common causes of hemolytic anemia secondary to enzyme deficiency: 1) G6PD deficiency; 2) Pyruvate kinase deficiency |
Pyruvate kinase is the last enzyme of glycolysis (PEP → pyruvate). ATP is produced in this step.
Pyruvate kinase deficiency → decreased ATP → decreased RBC Na/K ATPase activity → Na builds up inside RBC → RBC swelling + lysis.
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