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
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
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
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
National Board of Osteopathic Medical Examiners || ALIGNED WITH CURRENT
OSTEOPATHIC LICENSING BLUEPRINTS || BASIC SCIENCES AND CLINICAL
INTEGRATION || OSTEOPATHIC MANIPULATIVE MEDICINE REVIEW || COMPREHENSIVE
MEDICAL BOARD PREPARATION || 100% ORIGINAL VERIFIED PRACTICE CONTENT ||
CLINICAL REASONING AND APPLICATION-BASED ASSESSMENT || PREPARED FOR
PROFESSIONAL OSTEOPATHIC MEDICAL EXAMINATION USE || UPDATED FOR
CURRENT COMLEX-USA STANDARDS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
PROFESSIONAL STUDY EDITION
PREPARED FOR ADVANCED BOARD REVIEW
,━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Questions 1–10 — Biochemistry, Physiology & Cellular Medicine
Q1. A 22-year-old medical student participates in a prolonged fasting study. After 48
hours without caloric intake, laboratory evaluation demonstrates increased ketone
body production. Which enzyme is primarily responsible for regulating the rate-
limiting step of ketogenesis in hepatic mitochondria?
A. Acetyl-CoA carboxylase
B. HMG-CoA synthase
C. Pyruvate dehydrogenase
D. Carnitine palmitoyltransferase I
Correct Answer: 🔴 B. HMG-CoA synthase
Explanation: 🔹 HMG-CoA synthase catalyzes the rate-limiting step in ketogenesis by
converting acetyl-CoA into HMG-CoA within hepatic mitochondria. During prolonged
fasting, fatty acid oxidation increases, generating excess acetyl-CoA that is diverted into
ketone body production. Acetyl-CoA carboxylase is involved in fatty acid synthesis, not
ketogenesis. Pyruvate dehydrogenase links glycolysis to the TCA cycle and is inhibited
during fasting. Carnitine palmitoyltransferase I regulates fatty acid entry into
mitochondria but does not directly control ketone synthesis.
Q2. A 58-year-old man with chronic hypertension develops left ventricular
hypertrophy. Which cellular adaptation most directly explains the increased myocardial
wall thickness?
A. Hyperplasia of cardiac myocytes
B. Metaplasia of myocardial tissue
C. Hypertrophy through increased sarcomere synthesis
D. Dysplasia caused by pressure overload
Correct Answer: 🔴 C. Hypertrophy through increased sarcomere synthesis
Explanation: 🔹 Cardiac myocytes are permanent cells with minimal regenerative
capacity; therefore, chronic pressure overload results in hypertrophy rather than
hyperplasia. Increased sarcomere production enlarges individual myocytes, increasing
,ventricular wall thickness. Metaplasia refers to replacement of one mature cell type by
another and is not characteristic of myocardium. Dysplasia represents disordered growth
commonly associated with neoplasia rather than physiologic adaptation.
Q3. A patient with severe chronic diarrhea develops metabolic acidosis. Arterial blood
gas analysis reveals a decreased bicarbonate level. Which compensatory physiologic
response is expected?
A. Increased respiratory rate resulting in decreased PaCO₂
B. Decreased aldosterone secretion
C. Increased renal hydrogen retention
D. Reduced minute ventilation causing hypercapnia
Correct Answer: 🔴 A. Increased respiratory rate resulting in decreased PaCO₂
Explanation: 🔹 Metabolic acidosis stimulates peripheral chemoreceptors, leading to
compensatory hyperventilation and reduced arterial carbon dioxide concentration. This
respiratory compensation helps normalize pH. Decreased aldosterone would worsen acid
retention. Increased renal hydrogen retention is inappropriate because kidneys should
excrete more hydrogen ions. Reduced ventilation would increase PaCO₂ and exacerbate
acidosis.
Q4. A researcher investigates oxygen delivery in peripheral tissues. A rightward shift of
the oxygen-hemoglobin dissociation curve would most likely occur under which
condition?
A. Decreased temperature
B. Reduced 2,3-BPG concentration
C. Increased hydrogen ion concentration
D. Carbon monoxide exposure
Correct Answer: 🔴 C. Increased hydrogen ion concentration
Explanation: 🔹 Increased hydrogen ion concentration lowers hemoglobin affinity for
oxygen through the Bohr effect, shifting the dissociation curve to the right and
promoting oxygen unloading in tissues. Decreased temperature and reduced 2,3-BPG
, shift the curve leftward, increasing oxygen affinity. Carbon monoxide also shifts
remaining hemoglobin binding sites leftward while reducing oxygen-carrying capacity.
Q5. A 6-year-old child presents with recurrent bacterial infections and absent germinal
centers on lymph node biopsy. Laboratory studies reveal defective B-cell maturation.
Which immunoglobulin would most likely be severely decreased?
A. IgA
B. IgE
C. IgG
D. All immunoglobulin classes
Correct Answer: 🔴 D. All immunoglobulin classes
Explanation: 🔹 Failure of B-cell maturation impairs plasma cell development, resulting
in deficiency across all immunoglobulin classes. Germinal centers are sites of B-cell
proliferation and differentiation. Selective deficiencies such as isolated IgA deficiency do
not usually eliminate germinal centers entirely. Broad immunoglobulin reduction
predisposes patients to recurrent bacterial infections.
Q6. A pharmacologist administers a drug that competitively inhibits an enzyme
involved in folate synthesis in bacteria. Increasing substrate concentration partially
reverses the drug effect. Which pharmacologic principle best explains this finding?
A. Noncompetitive inhibition
B. Irreversible antagonism
C. Competitive inhibition
D. Allosteric enzyme activation
Correct Answer: 🔴 C. Competitive inhibition
Explanation: 🔹 Competitive inhibitors bind reversibly to the active site of enzymes and
can be overcome by increasing substrate concentration. Sulfonamides are classic
examples involving bacterial folate synthesis inhibition. Noncompetitive inhibitors bind
separate sites and are not overcome by substrate excess. Irreversible antagonists
permanently inactivate enzymes.
(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
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
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
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
National Board of Osteopathic Medical Examiners || ALIGNED WITH CURRENT
OSTEOPATHIC LICENSING BLUEPRINTS || BASIC SCIENCES AND CLINICAL
INTEGRATION || OSTEOPATHIC MANIPULATIVE MEDICINE REVIEW || COMPREHENSIVE
MEDICAL BOARD PREPARATION || 100% ORIGINAL VERIFIED PRACTICE CONTENT ||
CLINICAL REASONING AND APPLICATION-BASED ASSESSMENT || PREPARED FOR
PROFESSIONAL OSTEOPATHIC MEDICAL EXAMINATION USE || UPDATED FOR
CURRENT COMLEX-USA STANDARDS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
PROFESSIONAL STUDY EDITION
PREPARED FOR ADVANCED BOARD REVIEW
,━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Questions 1–10 — Biochemistry, Physiology & Cellular Medicine
Q1. A 22-year-old medical student participates in a prolonged fasting study. After 48
hours without caloric intake, laboratory evaluation demonstrates increased ketone
body production. Which enzyme is primarily responsible for regulating the rate-
limiting step of ketogenesis in hepatic mitochondria?
A. Acetyl-CoA carboxylase
B. HMG-CoA synthase
C. Pyruvate dehydrogenase
D. Carnitine palmitoyltransferase I
Correct Answer: 🔴 B. HMG-CoA synthase
Explanation: 🔹 HMG-CoA synthase catalyzes the rate-limiting step in ketogenesis by
converting acetyl-CoA into HMG-CoA within hepatic mitochondria. During prolonged
fasting, fatty acid oxidation increases, generating excess acetyl-CoA that is diverted into
ketone body production. Acetyl-CoA carboxylase is involved in fatty acid synthesis, not
ketogenesis. Pyruvate dehydrogenase links glycolysis to the TCA cycle and is inhibited
during fasting. Carnitine palmitoyltransferase I regulates fatty acid entry into
mitochondria but does not directly control ketone synthesis.
Q2. A 58-year-old man with chronic hypertension develops left ventricular
hypertrophy. Which cellular adaptation most directly explains the increased myocardial
wall thickness?
A. Hyperplasia of cardiac myocytes
B. Metaplasia of myocardial tissue
C. Hypertrophy through increased sarcomere synthesis
D. Dysplasia caused by pressure overload
Correct Answer: 🔴 C. Hypertrophy through increased sarcomere synthesis
Explanation: 🔹 Cardiac myocytes are permanent cells with minimal regenerative
capacity; therefore, chronic pressure overload results in hypertrophy rather than
hyperplasia. Increased sarcomere production enlarges individual myocytes, increasing
,ventricular wall thickness. Metaplasia refers to replacement of one mature cell type by
another and is not characteristic of myocardium. Dysplasia represents disordered growth
commonly associated with neoplasia rather than physiologic adaptation.
Q3. A patient with severe chronic diarrhea develops metabolic acidosis. Arterial blood
gas analysis reveals a decreased bicarbonate level. Which compensatory physiologic
response is expected?
A. Increased respiratory rate resulting in decreased PaCO₂
B. Decreased aldosterone secretion
C. Increased renal hydrogen retention
D. Reduced minute ventilation causing hypercapnia
Correct Answer: 🔴 A. Increased respiratory rate resulting in decreased PaCO₂
Explanation: 🔹 Metabolic acidosis stimulates peripheral chemoreceptors, leading to
compensatory hyperventilation and reduced arterial carbon dioxide concentration. This
respiratory compensation helps normalize pH. Decreased aldosterone would worsen acid
retention. Increased renal hydrogen retention is inappropriate because kidneys should
excrete more hydrogen ions. Reduced ventilation would increase PaCO₂ and exacerbate
acidosis.
Q4. A researcher investigates oxygen delivery in peripheral tissues. A rightward shift of
the oxygen-hemoglobin dissociation curve would most likely occur under which
condition?
A. Decreased temperature
B. Reduced 2,3-BPG concentration
C. Increased hydrogen ion concentration
D. Carbon monoxide exposure
Correct Answer: 🔴 C. Increased hydrogen ion concentration
Explanation: 🔹 Increased hydrogen ion concentration lowers hemoglobin affinity for
oxygen through the Bohr effect, shifting the dissociation curve to the right and
promoting oxygen unloading in tissues. Decreased temperature and reduced 2,3-BPG
, shift the curve leftward, increasing oxygen affinity. Carbon monoxide also shifts
remaining hemoglobin binding sites leftward while reducing oxygen-carrying capacity.
Q5. A 6-year-old child presents with recurrent bacterial infections and absent germinal
centers on lymph node biopsy. Laboratory studies reveal defective B-cell maturation.
Which immunoglobulin would most likely be severely decreased?
A. IgA
B. IgE
C. IgG
D. All immunoglobulin classes
Correct Answer: 🔴 D. All immunoglobulin classes
Explanation: 🔹 Failure of B-cell maturation impairs plasma cell development, resulting
in deficiency across all immunoglobulin classes. Germinal centers are sites of B-cell
proliferation and differentiation. Selective deficiencies such as isolated IgA deficiency do
not usually eliminate germinal centers entirely. Broad immunoglobulin reduction
predisposes patients to recurrent bacterial infections.
Q6. A pharmacologist administers a drug that competitively inhibits an enzyme
involved in folate synthesis in bacteria. Increasing substrate concentration partially
reverses the drug effect. Which pharmacologic principle best explains this finding?
A. Noncompetitive inhibition
B. Irreversible antagonism
C. Competitive inhibition
D. Allosteric enzyme activation
Correct Answer: 🔴 C. Competitive inhibition
Explanation: 🔹 Competitive inhibitors bind reversibly to the active site of enzymes and
can be overcome by increasing substrate concentration. Sulfonamides are classic
examples involving bacterial folate synthesis inhibition. Noncompetitive inhibitors bind
separate sites and are not overcome by substrate excess. Irreversible antagonists
permanently inactivate enzymes.
