COMLEX-USA Level 1 questions with correct answers 2026
Question (multiple-choice)
Correct Answer in Bold
Rationale in italics
COMLEX-USA Level 1 Practice Exam
General Principles & Biochemistry
1. A newborn presents with vomiting, lethargy, and hyperammonemia. Which
enzyme deficiency is most likely?
A. Ornithine transcarbamylase
B. Pyruvate dehydrogenase
C. Phenylalanine hydroxylase
D. Homogentisate oxidase
Answer: A. Ornithine transcarbamylase
This is the most common urea cycle disorder; X-linked, leading to inability to
eliminate ammonia.
2. Which amino acid is the precursor for serotonin?
A. Phenylalanine
B. Tyrosine
C. Tryptophan
D. Histidine
Answer: C. Tryptophan
Serotonin is synthesized from tryptophan via hydroxylation and
decarboxylation.
3. A patient develops lactic acidosis after receiving metformin. Which process
is most directly impaired?
A. Glycolysis
B. Gluconeogenesis
, C. Glycogenolysis
D. Lipolysis
Answer: B. Gluconeogenesis
Metformin inhibits hepatic gluconeogenesis, leading to increased lactate
accumulation.
4. Which vitamin deficiency is associated with megaloblastic anemia and
elevated methylmalonic acid?
A. Folate
B. Vitamin B6
C. Vitamin B12
D. Vitamin C
Answer: C. Vitamin B12
B12 deficiency causes megaloblastic anemia with neurologic symptoms and
high methylmalonic acid.
5. The rate-limiting enzyme of glycolysis is:
A. Hexokinase
B. Phosphofructokinase-1
C. Pyruvate kinase
D. Glucose-6-phosphatase
Answer: B. Phosphofructokinase-1
PFK-1 is the key regulatory enzyme of glycolysis, inhibited by ATP and
citrate.
Microbiology
6. A college student develops meningitis with a petechial rash. The most likely
organism is:
A. Streptococcus pneumoniae
B. Neisseria meningitidis
C. Listeria monocytogenes
D. Haemophilus influenzae type b
, Answer: B. Neisseria meningitidis
Causes meningitis in young adults with characteristic petechial rash due to
endotoxin.
7. Which bacteria produces toxin that inactivates elongation factor-2?
A. Clostridium tetani
B. Corynebacterium diphtheriae
C. Bordetella pertussis
D. Vibrio cholerae
Answer: B. Corynebacterium diphtheriae
The diphtheria toxin inhibits EF-2, blocking protein synthesis.
8. Which virus is most associated with congenital sensorineural hearing loss?
A. Rubella
B. Cytomegalovirus
C. Varicella
D. Parvovirus B19
Answer: B. Cytomegalovirus
CMV is the leading viral cause of congenital sensorineural hearing loss.
9. A patient with HIV develops pneumonia with ground-glass opacities on
chest x-ray. The likely pathogen is:
A. Pneumocystis jirovecii
B. Mycobacterium tuberculosis
C. Aspergillus fumigatus
D. Histoplasma capsulatum
Answer: A. Pneumocystis jirovecii
Pneumocystis causes opportunistic pneumonia with diffuse ground-glass
infiltrates.
Question (multiple-choice)
Correct Answer in Bold
Rationale in italics
COMLEX-USA Level 1 Practice Exam
General Principles & Biochemistry
1. A newborn presents with vomiting, lethargy, and hyperammonemia. Which
enzyme deficiency is most likely?
A. Ornithine transcarbamylase
B. Pyruvate dehydrogenase
C. Phenylalanine hydroxylase
D. Homogentisate oxidase
Answer: A. Ornithine transcarbamylase
This is the most common urea cycle disorder; X-linked, leading to inability to
eliminate ammonia.
2. Which amino acid is the precursor for serotonin?
A. Phenylalanine
B. Tyrosine
C. Tryptophan
D. Histidine
Answer: C. Tryptophan
Serotonin is synthesized from tryptophan via hydroxylation and
decarboxylation.
3. A patient develops lactic acidosis after receiving metformin. Which process
is most directly impaired?
A. Glycolysis
B. Gluconeogenesis
, C. Glycogenolysis
D. Lipolysis
Answer: B. Gluconeogenesis
Metformin inhibits hepatic gluconeogenesis, leading to increased lactate
accumulation.
4. Which vitamin deficiency is associated with megaloblastic anemia and
elevated methylmalonic acid?
A. Folate
B. Vitamin B6
C. Vitamin B12
D. Vitamin C
Answer: C. Vitamin B12
B12 deficiency causes megaloblastic anemia with neurologic symptoms and
high methylmalonic acid.
5. The rate-limiting enzyme of glycolysis is:
A. Hexokinase
B. Phosphofructokinase-1
C. Pyruvate kinase
D. Glucose-6-phosphatase
Answer: B. Phosphofructokinase-1
PFK-1 is the key regulatory enzyme of glycolysis, inhibited by ATP and
citrate.
Microbiology
6. A college student develops meningitis with a petechial rash. The most likely
organism is:
A. Streptococcus pneumoniae
B. Neisseria meningitidis
C. Listeria monocytogenes
D. Haemophilus influenzae type b
, Answer: B. Neisseria meningitidis
Causes meningitis in young adults with characteristic petechial rash due to
endotoxin.
7. Which bacteria produces toxin that inactivates elongation factor-2?
A. Clostridium tetani
B. Corynebacterium diphtheriae
C. Bordetella pertussis
D. Vibrio cholerae
Answer: B. Corynebacterium diphtheriae
The diphtheria toxin inhibits EF-2, blocking protein synthesis.
8. Which virus is most associated with congenital sensorineural hearing loss?
A. Rubella
B. Cytomegalovirus
C. Varicella
D. Parvovirus B19
Answer: B. Cytomegalovirus
CMV is the leading viral cause of congenital sensorineural hearing loss.
9. A patient with HIV develops pneumonia with ground-glass opacities on
chest x-ray. The likely pathogen is:
A. Pneumocystis jirovecii
B. Mycobacterium tuberculosis
C. Aspergillus fumigatus
D. Histoplasma capsulatum
Answer: A. Pneumocystis jirovecii
Pneumocystis causes opportunistic pneumonia with diffuse ground-glass
infiltrates.
