Kaplan USMLE Step 1 – Comprehensive Board Review
with Questions and Answers with Detailed Rationales
2026/2027 | 300+ Questions Verified
1. Cell Biology
A 7-year-old boy has developmental delay, coarse facial features, and
hepatosplenomegaly. Laboratory studies show increased activity of several
lysosomal enzymes in plasma. A defect in which cellular process most likely
explains this finding?
A. Addition of mannose-6-phosphate to lysosomal enzymes
B. Addition of ubiquitin to cytosolic proteins
C. N-linked glycosylation in the rough ER
D. Fusion of secretory vesicles with the plasma membrane
E. Translocation of proteins into mitochondria
Answer: A. Addition of mannose-6-phosphate to lysosomal enzymes
Rationale: Lysosomal enzymes receive mannose-6-phosphate tags in the Golgi
apparatus, directing them to lysosomes. Failure of this process causes I-cell
disease (mucolipidosis II), characterized by lysosomal enzyme accumulation in
plasma and lysosomal dysfunction.
2. Molecular Biology
A researcher studies a mutation that changes a DNA codon from UAU to UAA
after transcription. Which type of mutation has occurred?
A. Missense
B. Nonsense
C. Silent
D. Frameshift
E. Splice-site mutation
Answer: B. Nonsense
,Rationale: UAA is a stop codon. A mutation that converts a codon encoding an
amino acid into a premature stop codon is a nonsense mutation, producing a
truncated protein.
3. Genetics
A woman with an autosomal dominant disorder is heterozygous for the disease-
causing allele. Her partner is unaffected. What is the probability that their child
will inherit the disorder?
A. 0%
B. 10%
C. 25%
D. 50%
E. 100%
Answer: D. 50%
Rationale: A heterozygous affected parent has one affected and one normal allele.
Each child independently has a 50% probability of inheriting the affected allele.
4. Biochemistry
A patient develops severe fasting hypoglycemia, lactic acidosis, hyperuricemia,
and hepatomegaly. Which enzyme is most likely deficient?
A. Fructose-1,6-bisphosphatase
B. Glucose-6-phosphatase
C. Pyruvate carboxylase
D. Glycogen phosphorylase
E. Hexokinase
Answer: B. Glucose-6-phosphatase
Rationale: This presentation is characteristic of von Gierke disease (glycogen
storage disease type I). Glucose-6-phosphatase deficiency prevents conversion of
glucose-6-phosphate to free glucose during glycogenolysis and gluconeogenesis.
,5. Biochemistry
A child develops vomiting, lethargy, and hypoglycemia after consuming fruit juice.
Laboratory testing shows increased fructose-1-phosphate. Which enzyme is
deficient?
A. Fructokinase
B. Aldolase B
C. Galactokinase
D. Hexokinase
E. Glucose-6-phosphatase
Answer: B. Aldolase B
Rationale: Hereditary fructose intolerance results from aldolase B deficiency.
Fructose-1-phosphate accumulates and traps phosphate, impairing glycogenolysis
and gluconeogenesis.
6. Biochemistry
A patient with chronic alcohol use develops confusion, ophthalmoplegia, and gait
instability. Which enzyme is most likely impaired because of vitamin deficiency?
A. Pyruvate dehydrogenase
B. Lactate dehydrogenase
C. Hexokinase
D. Glucose-6-phosphatase
E. Succinate dehydrogenase
Answer: A. Pyruvate dehydrogenase
Rationale: Thiamine (vitamin B1) deficiency impairs enzymes requiring thiamine
pyrophosphate, including pyruvate dehydrogenase, α-ketoglutarate
dehydrogenase, and transketolase. Neurologic findings suggest Wernicke
encephalopathy.
, 7. Metabolism
During prolonged fasting, the liver converts fatty acids into ketone bodies. Which
tissue cannot use ketone bodies as a significant energy source?
A. Skeletal muscle
B. Cardiac muscle
C. Brain
D. Liver
E. Renal cortex
Answer: D. Liver
Rationale: The liver produces ketone bodies but cannot use them because it lacks
thiophorase (succinyl-CoA:acetoacetate CoA transferase).
8. Biochemistry
Which enzyme catalyzes the rate-limiting step of glycolysis?
A. Hexokinase
B. Phosphofructokinase-1
C. Pyruvate kinase
D. Aldolase
E. Phosphoglycerate kinase
Answer: B. Phosphofructokinase-1
Rationale: PFK-1 converts fructose-6-phosphate to fructose-1,6-bisphosphate and
is the major rate-limiting enzyme of glycolysis. ATP inhibits it, whereas AMP and
fructose-2,6-bisphosphate activate it.
9. Biochemistry
A patient has hemolytic anemia after exposure to an oxidizing medication. Which
metabolic pathway normally protects erythrocytes from oxidative damage?
with Questions and Answers with Detailed Rationales
2026/2027 | 300+ Questions Verified
1. Cell Biology
A 7-year-old boy has developmental delay, coarse facial features, and
hepatosplenomegaly. Laboratory studies show increased activity of several
lysosomal enzymes in plasma. A defect in which cellular process most likely
explains this finding?
A. Addition of mannose-6-phosphate to lysosomal enzymes
B. Addition of ubiquitin to cytosolic proteins
C. N-linked glycosylation in the rough ER
D. Fusion of secretory vesicles with the plasma membrane
E. Translocation of proteins into mitochondria
Answer: A. Addition of mannose-6-phosphate to lysosomal enzymes
Rationale: Lysosomal enzymes receive mannose-6-phosphate tags in the Golgi
apparatus, directing them to lysosomes. Failure of this process causes I-cell
disease (mucolipidosis II), characterized by lysosomal enzyme accumulation in
plasma and lysosomal dysfunction.
2. Molecular Biology
A researcher studies a mutation that changes a DNA codon from UAU to UAA
after transcription. Which type of mutation has occurred?
A. Missense
B. Nonsense
C. Silent
D. Frameshift
E. Splice-site mutation
Answer: B. Nonsense
,Rationale: UAA is a stop codon. A mutation that converts a codon encoding an
amino acid into a premature stop codon is a nonsense mutation, producing a
truncated protein.
3. Genetics
A woman with an autosomal dominant disorder is heterozygous for the disease-
causing allele. Her partner is unaffected. What is the probability that their child
will inherit the disorder?
A. 0%
B. 10%
C. 25%
D. 50%
E. 100%
Answer: D. 50%
Rationale: A heterozygous affected parent has one affected and one normal allele.
Each child independently has a 50% probability of inheriting the affected allele.
4. Biochemistry
A patient develops severe fasting hypoglycemia, lactic acidosis, hyperuricemia,
and hepatomegaly. Which enzyme is most likely deficient?
A. Fructose-1,6-bisphosphatase
B. Glucose-6-phosphatase
C. Pyruvate carboxylase
D. Glycogen phosphorylase
E. Hexokinase
Answer: B. Glucose-6-phosphatase
Rationale: This presentation is characteristic of von Gierke disease (glycogen
storage disease type I). Glucose-6-phosphatase deficiency prevents conversion of
glucose-6-phosphate to free glucose during glycogenolysis and gluconeogenesis.
,5. Biochemistry
A child develops vomiting, lethargy, and hypoglycemia after consuming fruit juice.
Laboratory testing shows increased fructose-1-phosphate. Which enzyme is
deficient?
A. Fructokinase
B. Aldolase B
C. Galactokinase
D. Hexokinase
E. Glucose-6-phosphatase
Answer: B. Aldolase B
Rationale: Hereditary fructose intolerance results from aldolase B deficiency.
Fructose-1-phosphate accumulates and traps phosphate, impairing glycogenolysis
and gluconeogenesis.
6. Biochemistry
A patient with chronic alcohol use develops confusion, ophthalmoplegia, and gait
instability. Which enzyme is most likely impaired because of vitamin deficiency?
A. Pyruvate dehydrogenase
B. Lactate dehydrogenase
C. Hexokinase
D. Glucose-6-phosphatase
E. Succinate dehydrogenase
Answer: A. Pyruvate dehydrogenase
Rationale: Thiamine (vitamin B1) deficiency impairs enzymes requiring thiamine
pyrophosphate, including pyruvate dehydrogenase, α-ketoglutarate
dehydrogenase, and transketolase. Neurologic findings suggest Wernicke
encephalopathy.
, 7. Metabolism
During prolonged fasting, the liver converts fatty acids into ketone bodies. Which
tissue cannot use ketone bodies as a significant energy source?
A. Skeletal muscle
B. Cardiac muscle
C. Brain
D. Liver
E. Renal cortex
Answer: D. Liver
Rationale: The liver produces ketone bodies but cannot use them because it lacks
thiophorase (succinyl-CoA:acetoacetate CoA transferase).
8. Biochemistry
Which enzyme catalyzes the rate-limiting step of glycolysis?
A. Hexokinase
B. Phosphofructokinase-1
C. Pyruvate kinase
D. Aldolase
E. Phosphoglycerate kinase
Answer: B. Phosphofructokinase-1
Rationale: PFK-1 converts fructose-6-phosphate to fructose-1,6-bisphosphate and
is the major rate-limiting enzyme of glycolysis. ATP inhibits it, whereas AMP and
fructose-2,6-bisphosphate activate it.
9. Biochemistry
A patient has hemolytic anemia after exposure to an oxidizing medication. Which
metabolic pathway normally protects erythrocytes from oxidative damage?
