Free Online USMLE Step 1 Questions and Answers 2

4. A 7-day-old neonate born to a 28-year-old woman is brought to the office due to progressive lethargy, vomiting, and poor feeding. The mother reports an uneventful pregnancy and perinatal course. She exclusively breastfeeds the
infant and has no medical problems in any of her other children. On examination, the infant is somnolent and dehydrated with decreased muscle tone. Laboratory studies reveal metabolic acidosis with an elevated anion gap,
ketosis, and hypoglycemia. Further evaluation reveals a markedly elevated propionic acid level due to defective conversion of propionyl-CoA to methylmalonyl-CoA. This patient is most likely unable to use which of the following amino acids for energy production?

A. Alanine
B. Aspartate
C. Glutamate
D. Lysine
E. Phenylalanine
F. Valine

Correct Answer: F

Answer Explanation:

(Choice A) Alanine transaminase catalyzes the transfer of an amino group from alanine to a-ketoglutarate, generating pyruvate that can be used for gluconeogenesis.
(Choice 8) Aspartate is a nonessential amino acid; it can be converted into oxaloacetate for use in the TCA cycle by aspartate transaminase.
(Choice C) Glutamate is deaminated by glutamate dehydrogenase to form the TCA cycle intermediate aketoglutarate.
(Choice D) Lysine and leucine are essential amino acids that are strictly ketogenic. They are metabolized into acetyl-CoA, which is a precursor for ketone bodies.
(Choice E) Phenylalanine is converted to tyrosine by the enzyme phenylalanine hydroxylase. Tyrosine is further converted into fumarate (TCA cycle intermediate) and acetoacetate (ketone body).

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5. As part of a research study investigating enzymatic activity in both normal and diseased liver tissue, hepatocytes are isolated from biopsy samples obtained from patients undergoing routine care at a local tertiary referral center.
The cells are homogenized and centrifuged to remove membrane components and organelles. Following subsequent rounds of centrifugation, the remaining supernatant contains only cytosol and cytosolic proteins.
Activity of which of the following enzymes will most likely be detectable in the supernatant of healthy liver cells?

A. 3-Hydroxy-3-methylglutaryl-CoA lyase
B. Omithine transcarbamylase
C. Pyruvate carboxylase
D. Succinate dehydrogenase
E. Transketolase

Correct Answer: E

Answer Explanation:

(Choice A) 3-Hydroxy-3-methylglutaryl-CoA (HMG CoA) lyase is a mitochondrial enzyme necessary for ketogenesis. It is also responsible for metabolism of the ketogenic amino acid, leucine.
(Choice B) Ornithine transcarbamylase catalyzes the combination of ornithine and carbamoyl phosphate to form citrulline in the urea cycle. This reaction occurs within the mitochondria.
(Choice C) Pyruvate carboxylase catalyzes the initial step in gluconeogenesis by converting pyruvate to oxaloacetate. This enzyme requires biotin as a cofactor, and functions within the mitochondria.
(Choice D) Succinate dehydrogenase is a TCA cycle enzyme that converts succinate to fumarate. It is an inner mitochondrial membrane protein and functions as part of the electron transport chain.

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6. A 43-year-old man prospecting for gold in Arizona becomes stuck in the desert after his truck breaks down. He brought a large supply of water
with him but only a few granola bars as food. After 3 days, he is able to flag down a passing vehicle and obtain transportation to the nearest settlement. During this ordeal, his liver begins to synthesize large quantities of glucose from source molecules such as alanine, lactate, and glycerol. As part of this
process, phosphoenolpyruvate is formed from oxaloacetate in a reaction that requires a specific nucleoside triphosphate as a cofactor. Which of the following reactions directly synthesizes this cofactor?

A. A
B. B
C. C
D. D
E. E
F. F
G. G
H. H

Correct Answer: E

Answer Explanation:

The majority of ATP used for cellular processes is generated by the oxidation of acetate in the tricarboxylic acid (TCA) cycle. The enzymes of the TCA cycle are located in the mitochondria and generate reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2) (Choices C, D , F, and H). These molecules drive the process of oxidative phosphorylation, which converts their reducing potential into high-energy ATP via the electron transport chain.
ATP can also be generated by substrate-level phosphorylation, which involves the direct transfer of a phosphate group from a reactive intermediate to a nucleotide diphosphate (eg, ADP, GDP). Succinyl-CoA synthetase converts succinyl-CoA to succinate and uses the high-energy thioester present in succinyl-CoA to drive GTP synthesis. This GTP can then be used to transphosphorylate ADP to ATP, or rt may be utilized by specific GTPhydrolyzing enzymes, such as phosphoenolpyruvate c-arboxykinase (converts oxaloacetate to phosphoenolpyruvate during gluconeogenesis).

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