COMSAE Phase 1 200 Questions with Answers & Rationales
QUESTIONS created for self-study and exam preparation, covering core COMSAE Phase 1 / COMLEX-USA
Level 1 basic science domains (biochemistry, genetics, microbiology/immunology, pathology, physiology,
anatomy, behavioral science, pharmacology, and osteopathic principles & practice).
Covers the core basic-science domains tested on COMSAE Phase 1 / COMLEX-USA Level 1: biochemistry, genetics,
microbiology/immunology, general & neoplastic pathology, physiology (cardio, respiratory, renal/acid-base, endocrine, GI),
anatomy (musculoskeletal, cardiothoracic, neuroanatomy), behavioral science, pharmacology (cardiovascular/autonomic,
CNS, antimicrobials), biostatistics/epidemiology, and osteopathic principles & practice (OMM, viscerosomatics).
Biochemistry & Molecular Biology
1. A deficiency of the enzyme responsible for converting phenylalanine to tyrosine causes which condition?
A. Alkaptonuria
B. Phenylketonuria (PKU)
C. Albinism
D. Homocystinuria
Correct Answer: B
Rationale: Phenylalanine hydroxylase deficiency causes PKU, leading to phenylalanine accumulation and intellectual
disability if untreated.
2. Which vitamin deficiency is classically associated with megaloblastic anemia and neurologic symptoms (subacute
combined degeneration)?
A. Vitamin B1 (thiamine)
B. Vitamin B12 (cobalamin)
C. Vitamin B6 (pyridoxine)
D. Vitamin C
Correct Answer: B
Rationale: B12 deficiency impairs DNA synthesis (megaloblastic anemia) and myelin maintenance, causing neurologic
deficits distinct from folate deficiency.
3. The rate-limiting enzyme of glycolysis is:
A. Hexokinase
B. Phosphofructokinase-1 (PFK-1)
C. Pyruvate kinase
D. Aldolase
Correct Answer: B
Rationale: PFK-1 catalyzes the committed, rate-limiting step of glycolysis and is allosterically regulated by ATP, AMP,
and citrate.
4. A patient with a deficiency in glucose-6-phosphate dehydrogenase (G6PD) is at risk for hemolysis when exposed to
oxidative stress because G6PD is essential for generating:
A. ATP
B. NADPH to maintain reduced glutathione
C. NADH
D. Acetyl-CoA
Correct Answer: B
Rationale: G6PD generates NADPH via the pentose phosphate pathway, which maintains glutathione in its reduced form
to protect RBCs from oxidative damage.
5. Which type of collagen is primarily found in bone?
A. Type I
B. Type II
, C. Type III
D. Type IV
Correct Answer: A
Rationale: Type I collagen is the most abundant type and predominates in bone, skin, and tendons.
6. A mutation causing a defect in fibrillin-1 is associated with which connective tissue disorder?
A. Ehlers-Danlos syndrome
B. Marfan syndrome
C. Osteogenesis imperfecta
D. Alport syndrome
Correct Answer: B
Rationale: Marfan syndrome results from fibrillin-1 mutations, affecting connective tissue integrity in the aorta, lens, and
skeleton.
7. The Lineweaver-Burk plot is used to determine which enzyme kinetic parameters?
A. pH optimum only
B. Km and Vmax
C. Temperature optimum
D. Molecular weight
Correct Answer: B
Rationale: The double-reciprocal Lineweaver-Burk plot linearizes Michaelis-Menten kinetics, allowing determination of
Km and Vmax.
8. A competitive enzyme inhibitor characteristically causes which change in kinetic parameters?
A. Increased Km, unchanged Vmax
B. Decreased Vmax, unchanged Km
C. Both Km and Vmax decrease
D. No change in either parameter
Correct Answer: A
Rationale: Competitive inhibitors increase apparent Km (more substrate needed to reach half-max velocity) but Vmax is
unchanged since it can be overcome with excess substrate.
9. Which amino acid is the precursor for serotonin synthesis?
A. Tyrosine
B. Tryptophan
C. Phenylalanine
D. Histidine
Correct Answer: B
Rationale: Tryptophan is hydroxylated and decarboxylated to form serotonin (5-HT).
10. A defect in the urea cycle enzyme ornithine transcarbamylase (OTC deficiency) results in accumulation of which
substance?
A. Ammonia
B. Phenylalanine
C. Homocysteine
D. Galactose
Correct Answer: A
Rationale: OTC deficiency, the most common urea cycle disorder, impairs ammonia detoxification, leading to
hyperammonemia.
Genetics
11. A disease with 100% penetrance affecting only heterozygotes, passed from an affected parent to roughly half of
offspring, follows which inheritance pattern?
, A. Autosomal recessive
B. Autosomal dominant
C. X-linked recessive
D. Mitochondrial
Correct Answer: B
Rationale: Autosomal dominant conditions affect heterozygotes and are transmitted to approximately 50% of offspring
when one parent is affected.
12. A condition in which only sons of a carrier mother are affected, and affected fathers never pass the disease to sons,
follows which inheritance pattern?
A. Autosomal dominant
B. Autosomal recessive
C. X-linked recessive
D. Mitochondrial (maternal)
Correct Answer: C
Rationale: X-linked recessive conditions affect males more often (only one X needed); affected fathers pass the mutant
allele to daughters (carriers), not sons.
13. Down syndrome (trisomy 21) most commonly results from:
A. Robertsonian translocation
B. Meiotic nondisjunction (typically maternal meiosis I)
C. Deletion
D. Mitotic nondisjunction only
Correct Answer: B
Rationale: Most cases of trisomy 21 arise from nondisjunction during maternal meiosis I, with incidence increasing with
maternal age.
14. A trinucleotide repeat expansion disorder that demonstrates 'anticipation' (earlier onset/increased severity in
successive generations) is:
A. Cystic fibrosis
B. Huntington disease
C. Sickle cell disease
D. Tay-Sachs disease
Correct Answer: B
Rationale: Huntington disease is caused by a CAG repeat expansion, and anticipation occurs due to further repeat
expansion during spermatogenesis.
15. Genomic imprinting explains why deletion of the same chromosomal region (15q11-13) causes different syndromes
depending on parent of origin. Deletion of the paternal copy causes:
A. Angelman syndrome
B. Prader-Willi syndrome
C. Down syndrome
D. Turner syndrome
Correct Answer: B
Rationale: Loss of the paternally expressed genes in this region causes Prader-Willi syndrome; loss of the maternal copy
causes Angelman syndrome.
16. A karyotype of 45,X in a phenotypic female with short stature and streak ovaries is consistent with:
A. Klinefelter syndrome
B. Turner syndrome
C. Down syndrome
D. Fragile X syndrome
Correct Answer: B
Rationale: Turner syndrome (45,X) presents with short stature, webbed neck, and gonadal dysgenesis (streak ovaries).
, 17. A 47,XXY karyotype in a phenotypic male is characteristic of:
A. Turner syndrome
B. Klinefelter syndrome
C. Edwards syndrome
D. Patau syndrome
Correct Answer: B
Rationale: Klinefelter syndrome (47,XXY) presents with testicular atrophy, gynecomastia, and infertility due to the extra
X chromosome.
18. Mitochondrial disorders are transmitted through which inheritance pattern?
A. Only from the father
B. Only from the mother (maternal inheritance)
C. Equally from both parents
D. Autosomal dominant only
Correct Answer: B
Rationale: Mitochondrial DNA is inherited exclusively from the mother via the oocyte cytoplasm, so mitochondrial
disorders show maternal inheritance.
19. A disease that appears to 'skip generations' but affects both males and females roughly equally, requiring two
carrier parents, is best explained by:
A. Autosomal dominant inheritance
B. Autosomal recessive inheritance
C. X-linked dominant inheritance
D. Y-linked inheritance
Correct Answer: B
Rationale: Autosomal recessive conditions typically require two carrier parents and can appear to skip generations since
carriers are usually unaffected.
20. Which technique is used to detect large chromosomal deletions, duplications, or translocations?
A. PCR only
B. Karyotyping/cytogenetic analysis (or FISH)
C. ELISA
D. Western blot
Correct Answer: B
Rationale: Karyotyping and FISH (fluorescence in situ hybridization) are used to visualize chromosomal structural
abnormalities.
Microbiology & Immunology
21. Gram-positive bacteria are distinguished from gram-negative bacteria primarily by differences in:
A. Presence of a nucleus
B. Cell wall structure (thick peptidoglycan layer retaining crystal violet)
C. Presence of flagella
D. Genome size
Correct Answer: B
Rationale: Gram-positive organisms have a thick peptidoglycan layer that retains the crystal violet-iodine complex,
appearing purple on Gram stain.
22. Toxic shock syndrome is classically associated with exotoxin production by which organism?
A. Streptococcus pneumoniae
B. Staphylococcus aureus (TSST-1)
C. Escherichia coli
D. Clostridium difficile
Correct Answer: B
QUESTIONS created for self-study and exam preparation, covering core COMSAE Phase 1 / COMLEX-USA
Level 1 basic science domains (biochemistry, genetics, microbiology/immunology, pathology, physiology,
anatomy, behavioral science, pharmacology, and osteopathic principles & practice).
Covers the core basic-science domains tested on COMSAE Phase 1 / COMLEX-USA Level 1: biochemistry, genetics,
microbiology/immunology, general & neoplastic pathology, physiology (cardio, respiratory, renal/acid-base, endocrine, GI),
anatomy (musculoskeletal, cardiothoracic, neuroanatomy), behavioral science, pharmacology (cardiovascular/autonomic,
CNS, antimicrobials), biostatistics/epidemiology, and osteopathic principles & practice (OMM, viscerosomatics).
Biochemistry & Molecular Biology
1. A deficiency of the enzyme responsible for converting phenylalanine to tyrosine causes which condition?
A. Alkaptonuria
B. Phenylketonuria (PKU)
C. Albinism
D. Homocystinuria
Correct Answer: B
Rationale: Phenylalanine hydroxylase deficiency causes PKU, leading to phenylalanine accumulation and intellectual
disability if untreated.
2. Which vitamin deficiency is classically associated with megaloblastic anemia and neurologic symptoms (subacute
combined degeneration)?
A. Vitamin B1 (thiamine)
B. Vitamin B12 (cobalamin)
C. Vitamin B6 (pyridoxine)
D. Vitamin C
Correct Answer: B
Rationale: B12 deficiency impairs DNA synthesis (megaloblastic anemia) and myelin maintenance, causing neurologic
deficits distinct from folate deficiency.
3. The rate-limiting enzyme of glycolysis is:
A. Hexokinase
B. Phosphofructokinase-1 (PFK-1)
C. Pyruvate kinase
D. Aldolase
Correct Answer: B
Rationale: PFK-1 catalyzes the committed, rate-limiting step of glycolysis and is allosterically regulated by ATP, AMP,
and citrate.
4. A patient with a deficiency in glucose-6-phosphate dehydrogenase (G6PD) is at risk for hemolysis when exposed to
oxidative stress because G6PD is essential for generating:
A. ATP
B. NADPH to maintain reduced glutathione
C. NADH
D. Acetyl-CoA
Correct Answer: B
Rationale: G6PD generates NADPH via the pentose phosphate pathway, which maintains glutathione in its reduced form
to protect RBCs from oxidative damage.
5. Which type of collagen is primarily found in bone?
A. Type I
B. Type II
, C. Type III
D. Type IV
Correct Answer: A
Rationale: Type I collagen is the most abundant type and predominates in bone, skin, and tendons.
6. A mutation causing a defect in fibrillin-1 is associated with which connective tissue disorder?
A. Ehlers-Danlos syndrome
B. Marfan syndrome
C. Osteogenesis imperfecta
D. Alport syndrome
Correct Answer: B
Rationale: Marfan syndrome results from fibrillin-1 mutations, affecting connective tissue integrity in the aorta, lens, and
skeleton.
7. The Lineweaver-Burk plot is used to determine which enzyme kinetic parameters?
A. pH optimum only
B. Km and Vmax
C. Temperature optimum
D. Molecular weight
Correct Answer: B
Rationale: The double-reciprocal Lineweaver-Burk plot linearizes Michaelis-Menten kinetics, allowing determination of
Km and Vmax.
8. A competitive enzyme inhibitor characteristically causes which change in kinetic parameters?
A. Increased Km, unchanged Vmax
B. Decreased Vmax, unchanged Km
C. Both Km and Vmax decrease
D. No change in either parameter
Correct Answer: A
Rationale: Competitive inhibitors increase apparent Km (more substrate needed to reach half-max velocity) but Vmax is
unchanged since it can be overcome with excess substrate.
9. Which amino acid is the precursor for serotonin synthesis?
A. Tyrosine
B. Tryptophan
C. Phenylalanine
D. Histidine
Correct Answer: B
Rationale: Tryptophan is hydroxylated and decarboxylated to form serotonin (5-HT).
10. A defect in the urea cycle enzyme ornithine transcarbamylase (OTC deficiency) results in accumulation of which
substance?
A. Ammonia
B. Phenylalanine
C. Homocysteine
D. Galactose
Correct Answer: A
Rationale: OTC deficiency, the most common urea cycle disorder, impairs ammonia detoxification, leading to
hyperammonemia.
Genetics
11. A disease with 100% penetrance affecting only heterozygotes, passed from an affected parent to roughly half of
offspring, follows which inheritance pattern?
, A. Autosomal recessive
B. Autosomal dominant
C. X-linked recessive
D. Mitochondrial
Correct Answer: B
Rationale: Autosomal dominant conditions affect heterozygotes and are transmitted to approximately 50% of offspring
when one parent is affected.
12. A condition in which only sons of a carrier mother are affected, and affected fathers never pass the disease to sons,
follows which inheritance pattern?
A. Autosomal dominant
B. Autosomal recessive
C. X-linked recessive
D. Mitochondrial (maternal)
Correct Answer: C
Rationale: X-linked recessive conditions affect males more often (only one X needed); affected fathers pass the mutant
allele to daughters (carriers), not sons.
13. Down syndrome (trisomy 21) most commonly results from:
A. Robertsonian translocation
B. Meiotic nondisjunction (typically maternal meiosis I)
C. Deletion
D. Mitotic nondisjunction only
Correct Answer: B
Rationale: Most cases of trisomy 21 arise from nondisjunction during maternal meiosis I, with incidence increasing with
maternal age.
14. A trinucleotide repeat expansion disorder that demonstrates 'anticipation' (earlier onset/increased severity in
successive generations) is:
A. Cystic fibrosis
B. Huntington disease
C. Sickle cell disease
D. Tay-Sachs disease
Correct Answer: B
Rationale: Huntington disease is caused by a CAG repeat expansion, and anticipation occurs due to further repeat
expansion during spermatogenesis.
15. Genomic imprinting explains why deletion of the same chromosomal region (15q11-13) causes different syndromes
depending on parent of origin. Deletion of the paternal copy causes:
A. Angelman syndrome
B. Prader-Willi syndrome
C. Down syndrome
D. Turner syndrome
Correct Answer: B
Rationale: Loss of the paternally expressed genes in this region causes Prader-Willi syndrome; loss of the maternal copy
causes Angelman syndrome.
16. A karyotype of 45,X in a phenotypic female with short stature and streak ovaries is consistent with:
A. Klinefelter syndrome
B. Turner syndrome
C. Down syndrome
D. Fragile X syndrome
Correct Answer: B
Rationale: Turner syndrome (45,X) presents with short stature, webbed neck, and gonadal dysgenesis (streak ovaries).
, 17. A 47,XXY karyotype in a phenotypic male is characteristic of:
A. Turner syndrome
B. Klinefelter syndrome
C. Edwards syndrome
D. Patau syndrome
Correct Answer: B
Rationale: Klinefelter syndrome (47,XXY) presents with testicular atrophy, gynecomastia, and infertility due to the extra
X chromosome.
18. Mitochondrial disorders are transmitted through which inheritance pattern?
A. Only from the father
B. Only from the mother (maternal inheritance)
C. Equally from both parents
D. Autosomal dominant only
Correct Answer: B
Rationale: Mitochondrial DNA is inherited exclusively from the mother via the oocyte cytoplasm, so mitochondrial
disorders show maternal inheritance.
19. A disease that appears to 'skip generations' but affects both males and females roughly equally, requiring two
carrier parents, is best explained by:
A. Autosomal dominant inheritance
B. Autosomal recessive inheritance
C. X-linked dominant inheritance
D. Y-linked inheritance
Correct Answer: B
Rationale: Autosomal recessive conditions typically require two carrier parents and can appear to skip generations since
carriers are usually unaffected.
20. Which technique is used to detect large chromosomal deletions, duplications, or translocations?
A. PCR only
B. Karyotyping/cytogenetic analysis (or FISH)
C. ELISA
D. Western blot
Correct Answer: B
Rationale: Karyotyping and FISH (fluorescence in situ hybridization) are used to visualize chromosomal structural
abnormalities.
Microbiology & Immunology
21. Gram-positive bacteria are distinguished from gram-negative bacteria primarily by differences in:
A. Presence of a nucleus
B. Cell wall structure (thick peptidoglycan layer retaining crystal violet)
C. Presence of flagella
D. Genome size
Correct Answer: B
Rationale: Gram-positive organisms have a thick peptidoglycan layer that retains the crystal violet-iodine complex,
appearing purple on Gram stain.
22. Toxic shock syndrome is classically associated with exotoxin production by which organism?
A. Streptococcus pneumoniae
B. Staphylococcus aureus (TSST-1)
C. Escherichia coli
D. Clostridium difficile
Correct Answer: B
