Question of the day
A 20-year-old, African-American male military recruit is about to be sent on his assignment. In preparation for his tour of duty, he is given a prophylactic dose of primaquine to prevent malaria. Several days after he begins taking the drug, he develops fatigue and hemolytic anemia. Which of the following enzymes is likely deficient?
C. Glucose-6-P dehydrogenase
D. Pyruvate kinase
E. Aldolase B
Answer- The correct answer is- C-Glucose-6-P dehydrogenase deficiency
The patient has presented with primaquine induced hemolytic anemia. Primaquine is an antimalarial drug known to trigger an attack of hemolysis in patients with underlying glucose-6-P dehydrogenase deficiency.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common disease-producing enzymopathy in humans which is inherited as an X-linked disorder. The Acute Hemolytic Anemia can develop as a result of three types of triggers: (1) fava beans, (2) infections, and (3) drugs.
The drugs that precipitate an attack of hemolytic anemia are- antibiotics, antipyretics and antimalarials
Glucose 6-phosphate dehydrogenase (G6PD) is an enzyme critical in the redox metabolism of all aerobic cells .In red cells, its role is even more critical because it is the only source of reduced nicotinamide adenine dinucleotide phosphate (NADPH), which, directly and via reduced glutathione (GSH), defends these cells against oxidative stress.
Figure- Role of G-6-P-Dehydrogenase in decomposition of H2 O2
NADPH is a required cofactor in many biosynthetic reactions which also maintains glutathione in its reduced form. Reduced glutathione acts as a scavenger for dangerous oxidative metabolites in the cell. With the help of the enzyme glutathione peroxidase, reduced glutathione converts harmful hydrogen peroxide to water (figure). G6PD deficiency is a prime example of a hemolytic anemia due to interaction between an intracorpuscular and an extracorpuscular cause, because in the majority of cases hemolysis is triggered by an exogenous agent. People deficient in glucose-6-phosphate dehydrogenase (G6PD) are not prescribed oxidative drugs, because their red blood cells undergo rapid hemolysis under this stress. Although in G6PD-deficient subjects there is a decrease in G6PD activity in most tissues, this is less marked than in red cells, and it does not seem to produce symptoms.
Identification and discontinuation of the precipitating agent is critical in cases of glucose-6-phosphate dehydrogenase (G6PD) deficiency. Most individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency do not need treatment.
Galactokinase is an enzyme of galactose metabolism. Galactokinase deficiency causes benign galactosemia and galactosuria (excessive galactose concentration in blood and urine respectively); it is not associated with hemolytic anemia.
Fructokinase is an enzyme of fructose metabolism. Its deficiency cannot cause hemolytic anemia. Its deficiency is associated with fructosuria, it is a benign condition.
Pyruvate kinase deficiency can cause hemolytic anemia, but since the patient had the attack after primaquine, so the most likely cause could be glucose-6-p dehydrogenase deficiency.
There are two isoenzymes of Aldolase- Aldolase A and B. Aldolase A is an enzyme of glycolytic pathway that catalyzes the cleavage of fructose 1, 6 bisphosphate to glyceraldehyde-3-P anddDihydroxy acetone phosphate. Aldolase B is an enzyme of fructose metabolism, its deficiency causes hereditary fructose intolerance. It is not associated with hemolytic anemia.
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