From the Research
To prepare for the USMLE Step 1 biochemistry exam, it's essential to practice with relevant questions that cover various biochemical pathways and their disorders. Here are five practice questions with answers to help with your preparation:
- Question 1: A 3-month-old boy presents with vomiting, lethargy, and metabolic acidosis during a febrile illness. Laboratory studies show elevated blood ammonia levels and orotic aciduria. Which enzyme deficiency is most likely responsible for this presentation? Answer: The patient likely has ornithine transcarbamylase (OTC) deficiency, the most common urea cycle disorder, as noted in various studies on metabolic disorders 1, 2.
- Question 2: A patient with alcoholism develops Wernicke encephalopathy. Which enzyme is most directly affected by thiamine deficiency in this condition? Answer: Pyruvate dehydrogenase complex is directly affected by thiamine deficiency in Wernicke encephalopathy, as thiamine pyrophosphate is a cofactor for this enzyme complex, linking glycolysis to the TCA cycle, a crucial step in energy metabolism 3.
- Question 3: A newborn screening test reveals elevated phenylalanine levels. Which metabolic pathway is defective in this patient? Answer: The patient has phenylketonuria (PKU), caused by deficiency of phenylalanine hydroxylase, which normally converts phenylalanine to tyrosine, a defect that can lead to severe neurological manifestations if not treated promptly 4.
- Question 4: A 45-year-old man presents with recurrent kidney stones and gout. Laboratory studies show hyperuricemia. Which enzyme defect would explain increased de novo purine synthesis? Answer: Glucose-6-phosphatase deficiency (von Gierke disease) would explain increased de novo purine synthesis leading to hyperuricemia, as seen in patients with glycogen storage diseases, highlighting the importance of glucose metabolism in purine synthesis 2.
- Question 5: A patient with Lesch-Nyhan syndrome presents with self-mutilation, choreoathetosis, and hyperuricemia. Which enzyme is deficient? Answer: Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency causes Lesch-Nyhan syndrome, an X-linked recessive disorder that impairs purine salvage, leading to increased de novo purine synthesis and subsequent hyperuricemia, emphasizing the role of purine metabolism in neurological disorders 1. Practicing with these types of questions and understanding the underlying biochemical pathways and their clinical implications is crucial for success on the USMLE Step 1 exam.