A 30-year-old man presents to the emergency department with shortness of breath and dark urine for the last 1 day. He has recently returned from a vacation in Southeast Asia. He was prescribed medications by the local doctor for urinary tract infection. Vital signs are within normal limits are normal except for a heart rate of 115 beats/minute. Physical examination is unremarkable except for tachycardia. Laboratory studies show hemoglobin of 8 g/dL, normal mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC), elevated lactate dehydrogenase (LDH), and increased urine urobilinogen. Peripheral smear is notable for bite cells.
Which of the following enzymes is affected by the cofactor deficiency in this patient?
E) Glutathione reductase
The patient is presenting with acute hemolytic anemia that is most likely precipitated by an antibiotic containing a sulfa group (e.g., nitrofurantoin, trimethoprim-sulfamethoxazole) prescribed for his urinary tract infection. Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency have low levels of G6PD, an enzyme that protects red blood cells from oxidative stress, leading to increased hemolysis in situations of stress. G6PD deficiency leads to decreased synthesis of NADPH and glutathione from the pentose phosphate pathway. Red blood cells contain relatively high concentrations of reduced glutathione (GSH), thereby protecting against oxidant injury. Under normal circumstances, GSH levels are restored by glutathione reductase which catalyzes the reduction of oxidized glutathione to GSH. This reaction requires the NADPH generated by G6PD. In patients with G6PD deficiency, hemolysis often results from exposure to oxidative stress such as infection, sulfonamide drugs, acidosis, and fava beans.
Answer choice A: Glutamate decarboxylase, is incorrect. Glutamate decarboxylase is an enzyme that catalyzes the conversion of glutamate to GABA and carbon dioxide. Glutamate decarboxylase uses pyridoxal-phosphate (PLP) as a cofactor and not NADPH.
Answer choice B: Glutamate oxaloacetate decarboxylase, is incorrect. This enzyme metabolizes glutamate and ammonia into glutamine. This enzyme does no need NADPH.
Answer choice C: Glutaminase, is incorrect. Glutaminase is an amidohydrolase enzyme that generates glutamate from glutamine which is important for many cell cycles (e.g., Kreb cycle, urea cycle). NADPH is not necessary for this enzyme to work.
Answer choice D: Glutathione peroxidase, is incorrect. Glutathione peroxidase catalyzes the reduction of various hydroperoxides (e.g., H2O2) to H2O via
oxidation of reduced glutathione without the need for NADPH directly.
Key Learning Point
Red blood cells contain relatively high concentrations of reduced glutathione (GSH), thereby protecting against oxidant injury. Under normal circumstances, GSH levels are restored by glutathione reductase which catalyzes the reduction of oxidized glutathione to GSH. This reaction requires the NADPH generated by G6PD. In patients with G6PD deficiency, hemolysis often results from exposure to oxidative stress such as infection, sulfonamide drugs, acidosis, and fava beans.
