COMPREHENSIVE OSTEOPATHIC MEDICAL SELF-ASSESSMENT EXAMINATION
(COMSAE) PHASE 1 FORM 116 COMPLETE PRACTICE EXAM QUESTIONS AND
ANSWERS | VERIFIED SOLUTIONS | UPDATED 2026/2027 STUDY GUIDE
Examiner/Administrator: National Board of Osteopathic Medical Examiners (NBOME)
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
COMPREHENSIVE OSTEOPATHIC
MEDICAL SELF-ASSESSMENT EXAMINATION
(COMSAE) PHASE 1 FORM 116
2026/2027 EDITION
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
COMPLETE PRACTICE EXAM
100 MULTIPLE-CHOICE QUESTIONS
EXACT OFFICIAL COUNT: 100 QUESTIONS
PASSING SCORE: 70%
TESTING TIME: 120 MINUTES
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
NBOME-STYLE OSTEOPATHIC MEDICAL ASSESSMENT || ALIGNED WITH CURRENT
COMLEX-USA LEVEL 1 BLUEPRINTS || SYSTEMS-BASED INTEGRATED BASIC SCIENCES ||
OSTEOPATHIC PRINCIPLES & PRACTICE || CLINICAL REASONING & DIAGNOSTIC
APPLICATION || 100% ORIGINAL VERIFIED STUDY MATERIAL || COMPREHENSIVE
MEDICAL BOARD PREPARATION || UPDATED PATHOLOGY, PHARMACOLOGY &
MICROBIOLOGY REVIEW || PREPARED FOR PROFESSIONAL EXAMINATION USE
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
PROFESSIONAL ACADEMIC EDITION
PREPARED FOR ADVANCED MEDICAL REVIEW
AND BOARD EXAM PREPARATION
,━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Questions 1–8 → Biochemistry & Molecular Medicine
Q1. A 6-month-old infant presents with progressive hypotonia, developmental delay,
hepatomegaly, and fasting hypoglycemia. Laboratory analysis demonstrates elevated
glycogen concentration with abnormally short outer glycogen chains. Deficiency of
which enzyme is most likely responsible for this condition?
A. Glycogen phosphorylase
B. Branching enzyme
C. Debranching enzyme
D. Glucose-6-phosphatase
Correct Answer: 🔴 C. Debranching enzyme
Explanation: 🔹 This presentation is most consistent with Glycogen Storage Disease Type
III (Cori disease), caused by deficiency of the glycogen debranching enzyme. Patients
develop accumulation of abnormal glycogen with short outer chains and experience
fasting hypoglycemia, hepatomegaly, and muscle weakness. Glycogen phosphorylase
deficiency causes McArdle disease, primarily affecting skeletal muscle. Branching enzyme
deficiency causes Andersen disease with progressive cirrhosis. Glucose-6-phosphatase
deficiency causes von Gierke disease with severe lactic acidosis and hyperuricemia.
Q2. A researcher inhibits RNA polymerase II in cultured human cells. Which cellular
process would be most directly impaired?
A. rRNA synthesis
B. tRNA synthesis
C. mRNA transcription
D. DNA replication
Correct Answer: 🔴 C. mRNA transcription
Explanation: 🔹 RNA polymerase II is responsible for synthesis of messenger RNA in
eukaryotic cells. RNA polymerase I synthesizes most rRNA, while RNA polymerase III
synthesizes tRNA and 5S rRNA. DNA replication is mediated by DNA polymerases rather
,than RNA polymerase II. Inhibition of RNA polymerase II significantly disrupts protein
synthesis due to reduced mRNA availability.
Q3. A 42-year-old man with chronic alcoholism develops confusion, ophthalmoplegia,
and gait instability. Deficiency of thiamine most directly impairs which metabolic
pathway?
A. Beta-oxidation
B. Pentose phosphate pathway
C. Citric acid cycle oxidative decarboxylation reactions
D. Glycogenolysis
Correct Answer: 🔴 C. Citric acid cycle oxidative decarboxylation reactions
Explanation: 🔹 Thiamine (vitamin B1) is a cofactor for pyruvate dehydrogenase, alpha-
ketoglutarate dehydrogenase, branched-chain ketoacid dehydrogenase, and
transketolase. Deficiency impairs oxidative decarboxylation within aerobic metabolism,
leading to neurologic dysfunction characteristic of Wernicke encephalopathy. Beta-
oxidation primarily requires carnitine and riboflavin-related cofactors. Glycogenolysis is
not thiamine-dependent.
Q4. A patient develops severe hemolytic anemia after taking primaquine for malaria
prophylaxis. Laboratory studies reveal Heinz bodies and bite cells. Which enzyme
deficiency most likely predisposed this patient to hemolysis?
A. Pyruvate kinase
B. Glucose-6-phosphate dehydrogenase
C. Hexokinase
D. Lactate dehydrogenase
Correct Answer: 🔴 B. Glucose-6-phosphate dehydrogenase
Explanation: 🔹 G6PD deficiency reduces the ability of erythrocytes to generate NADPH
through the pentose phosphate pathway, impairing glutathione regeneration and
increasing oxidative susceptibility. Primaquine is a classic oxidative stressor capable of
, precipitating hemolysis. Heinz bodies represent denatured hemoglobin, while bite cells
result from splenic macrophage removal of damaged hemoglobin.
Q5. A mutation leads to substitution of valine for glutamic acid at the sixth position of
the beta-globin chain. Which change in protein structure is primarily responsible for
the resulting disease manifestation?
A. Loss of quaternary structure
B. Increased alpha-helix formation
C. Hydrophobic polymerization under low oxygen conditions
D. Disruption of peptide bond formation
Correct Answer: 🔴 C. Hydrophobic polymerization under low oxygen conditions
Explanation: 🔹 Sickle cell disease results from a missense mutation causing hydrophobic
valine substitution. Under deoxygenated conditions, hemoglobin S polymerizes,
distorting red blood cells into sickled shapes that cause vaso-occlusion and hemolysis.
Peptide bonds remain intact, and quaternary structure is not entirely lost. The disease
specifically arises from abnormal intermolecular interactions during deoxygenation.
Q6. A patient with hypercholesterolemia is treated with a medication that
competitively inhibits HMG-CoA reductase. Which compound is directly reduced as a
consequence?
A. Mevalonate
B. Acetyl-CoA
C. Farnesyl pyrophosphate
D. Squalene
Correct Answer: 🔴 A. Mevalonate
Explanation: 🔹 HMG-CoA reductase converts HMG-CoA to mevalonate, the rate-
limiting step in cholesterol synthesis. Statins inhibit this enzyme and thereby decrease
intracellular cholesterol production. Farnesyl pyrophosphate and squalene are
downstream intermediates. Acetyl-CoA participates earlier in metabolism and is not
directly reduced by statin therapy.
(COMSAE) PHASE 1 FORM 116 COMPLETE PRACTICE EXAM QUESTIONS AND
ANSWERS | VERIFIED SOLUTIONS | UPDATED 2026/2027 STUDY GUIDE
Examiner/Administrator: National Board of Osteopathic Medical Examiners (NBOME)
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
COMPREHENSIVE OSTEOPATHIC
MEDICAL SELF-ASSESSMENT EXAMINATION
(COMSAE) PHASE 1 FORM 116
2026/2027 EDITION
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
COMPLETE PRACTICE EXAM
100 MULTIPLE-CHOICE QUESTIONS
EXACT OFFICIAL COUNT: 100 QUESTIONS
PASSING SCORE: 70%
TESTING TIME: 120 MINUTES
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
NBOME-STYLE OSTEOPATHIC MEDICAL ASSESSMENT || ALIGNED WITH CURRENT
COMLEX-USA LEVEL 1 BLUEPRINTS || SYSTEMS-BASED INTEGRATED BASIC SCIENCES ||
OSTEOPATHIC PRINCIPLES & PRACTICE || CLINICAL REASONING & DIAGNOSTIC
APPLICATION || 100% ORIGINAL VERIFIED STUDY MATERIAL || COMPREHENSIVE
MEDICAL BOARD PREPARATION || UPDATED PATHOLOGY, PHARMACOLOGY &
MICROBIOLOGY REVIEW || PREPARED FOR PROFESSIONAL EXAMINATION USE
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
PROFESSIONAL ACADEMIC EDITION
PREPARED FOR ADVANCED MEDICAL REVIEW
AND BOARD EXAM PREPARATION
,━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Questions 1–8 → Biochemistry & Molecular Medicine
Q1. A 6-month-old infant presents with progressive hypotonia, developmental delay,
hepatomegaly, and fasting hypoglycemia. Laboratory analysis demonstrates elevated
glycogen concentration with abnormally short outer glycogen chains. Deficiency of
which enzyme is most likely responsible for this condition?
A. Glycogen phosphorylase
B. Branching enzyme
C. Debranching enzyme
D. Glucose-6-phosphatase
Correct Answer: 🔴 C. Debranching enzyme
Explanation: 🔹 This presentation is most consistent with Glycogen Storage Disease Type
III (Cori disease), caused by deficiency of the glycogen debranching enzyme. Patients
develop accumulation of abnormal glycogen with short outer chains and experience
fasting hypoglycemia, hepatomegaly, and muscle weakness. Glycogen phosphorylase
deficiency causes McArdle disease, primarily affecting skeletal muscle. Branching enzyme
deficiency causes Andersen disease with progressive cirrhosis. Glucose-6-phosphatase
deficiency causes von Gierke disease with severe lactic acidosis and hyperuricemia.
Q2. A researcher inhibits RNA polymerase II in cultured human cells. Which cellular
process would be most directly impaired?
A. rRNA synthesis
B. tRNA synthesis
C. mRNA transcription
D. DNA replication
Correct Answer: 🔴 C. mRNA transcription
Explanation: 🔹 RNA polymerase II is responsible for synthesis of messenger RNA in
eukaryotic cells. RNA polymerase I synthesizes most rRNA, while RNA polymerase III
synthesizes tRNA and 5S rRNA. DNA replication is mediated by DNA polymerases rather
,than RNA polymerase II. Inhibition of RNA polymerase II significantly disrupts protein
synthesis due to reduced mRNA availability.
Q3. A 42-year-old man with chronic alcoholism develops confusion, ophthalmoplegia,
and gait instability. Deficiency of thiamine most directly impairs which metabolic
pathway?
A. Beta-oxidation
B. Pentose phosphate pathway
C. Citric acid cycle oxidative decarboxylation reactions
D. Glycogenolysis
Correct Answer: 🔴 C. Citric acid cycle oxidative decarboxylation reactions
Explanation: 🔹 Thiamine (vitamin B1) is a cofactor for pyruvate dehydrogenase, alpha-
ketoglutarate dehydrogenase, branched-chain ketoacid dehydrogenase, and
transketolase. Deficiency impairs oxidative decarboxylation within aerobic metabolism,
leading to neurologic dysfunction characteristic of Wernicke encephalopathy. Beta-
oxidation primarily requires carnitine and riboflavin-related cofactors. Glycogenolysis is
not thiamine-dependent.
Q4. A patient develops severe hemolytic anemia after taking primaquine for malaria
prophylaxis. Laboratory studies reveal Heinz bodies and bite cells. Which enzyme
deficiency most likely predisposed this patient to hemolysis?
A. Pyruvate kinase
B. Glucose-6-phosphate dehydrogenase
C. Hexokinase
D. Lactate dehydrogenase
Correct Answer: 🔴 B. Glucose-6-phosphate dehydrogenase
Explanation: 🔹 G6PD deficiency reduces the ability of erythrocytes to generate NADPH
through the pentose phosphate pathway, impairing glutathione regeneration and
increasing oxidative susceptibility. Primaquine is a classic oxidative stressor capable of
, precipitating hemolysis. Heinz bodies represent denatured hemoglobin, while bite cells
result from splenic macrophage removal of damaged hemoglobin.
Q5. A mutation leads to substitution of valine for glutamic acid at the sixth position of
the beta-globin chain. Which change in protein structure is primarily responsible for
the resulting disease manifestation?
A. Loss of quaternary structure
B. Increased alpha-helix formation
C. Hydrophobic polymerization under low oxygen conditions
D. Disruption of peptide bond formation
Correct Answer: 🔴 C. Hydrophobic polymerization under low oxygen conditions
Explanation: 🔹 Sickle cell disease results from a missense mutation causing hydrophobic
valine substitution. Under deoxygenated conditions, hemoglobin S polymerizes,
distorting red blood cells into sickled shapes that cause vaso-occlusion and hemolysis.
Peptide bonds remain intact, and quaternary structure is not entirely lost. The disease
specifically arises from abnormal intermolecular interactions during deoxygenation.
Q6. A patient with hypercholesterolemia is treated with a medication that
competitively inhibits HMG-CoA reductase. Which compound is directly reduced as a
consequence?
A. Mevalonate
B. Acetyl-CoA
C. Farnesyl pyrophosphate
D. Squalene
Correct Answer: 🔴 A. Mevalonate
Explanation: 🔹 HMG-CoA reductase converts HMG-CoA to mevalonate, the rate-
limiting step in cholesterol synthesis. Statins inhibit this enzyme and thereby decrease
intracellular cholesterol production. Farnesyl pyrophosphate and squalene are
downstream intermediates. Acetyl-CoA participates earlier in metabolism and is not
directly reduced by statin therapy.
