COMPREHENSIVE OSTEOPATHIC MEDICAL SELF-ASSESSMENT EXAMINATION
(COMSAE) PHASE 1 FORM 111 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 111
2026/2027 EDITION
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
COMPLETE PRACTICE EXAM
100 MULTIPLE-CHOICE QUESTIONS
EXACT OFFICIAL COUNT: 100 QUESTIONS
PASSING SCORE: 70%
TESTING TIME: 120 MINUTES
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
NBOME BLUEPRINT-ALIGNED COMPREHENSIVE PRACTICE EXAMINATION ||
OSTEOPATHIC PRINCIPLES & CLINICAL SCIENCES || INTEGRATED BASIC AND CLINICAL
MEDICINE REVIEW || PROFESSIONAL BOARD PREPARATION RESOURCE || 100%
ORIGINAL VERIFIED PRACTICE CONTENT || COMPREHENSIVE MEDICAL ASSESSMENT
PREPARATION || DESIGNED FOR COMLEX-USA LEVEL 1 READINESS || PROFESSIONAL
EXAMINATION USE ONLY
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Questions 1–10 — Biochemistry & Molecular Medicine
Q1. A 6-month-old infant presents with seizures, developmental delay, and a musty
body odor. Laboratory testing demonstrates elevated phenylalanine levels. The patient
was born after an uncomplicated pregnancy and was exclusively breastfed. Which of
the following best explains the pathophysiology underlying this condition?
,A. Deficiency of homogentisate oxidase resulting in connective tissue deposition
B. Impaired conversion of phenylalanine to tyrosine due to tetrahydrobiopterin-related
dysfunction
C. Defective branched-chain α-ketoacid dehydrogenase complex activity
D. Inability to transport neutral amino acids across intestinal epithelial cells
Correct Answer: 🔴 B. Impaired conversion of phenylalanine to tyrosine due to
tetrahydrobiopterin-related dysfunction
Explanation: 🔹 Phenylketonuria (PKU) results from deficient phenylalanine
hydroxylase activity or defects in tetrahydrobiopterin (BH4), a required cofactor.
Accumulation of phenylalanine leads to neurotoxicity, developmental delay, seizures,
eczema, and a characteristic musty odor. Choice A describes alkaptonuria, Choice C
refers to maple syrup urine disease, and Choice D describes Hartnup disease. Early
diagnosis through newborn screening prevents severe neurologic complications
through dietary restriction of phenylalanine.
Q2. A researcher is studying an enzyme involved in glycolysis. She observes that
increasing substrate concentration beyond a certain point fails to increase reaction
velocity. Which parameter has most likely been reached?
A. Km
B. Ki
C. Vmax
D. Ka
Correct Answer: 🔴 C. Vmax
Explanation: 🔹 Vmax represents the maximum reaction velocity achieved when all
enzyme active sites are saturated with substrate. Beyond this point, increasing
substrate concentration cannot further accelerate the reaction. Km reflects substrate
affinity, Ki is the inhibition constant, and Ka relates to acid dissociation. This
principle is fundamental in understanding enzyme kinetics and pharmacologic
interactions.
,Q3. A 45-year-old man with chronic alcoholism presents with confusion,
ophthalmoplegia, and ataxia. Deficiency of which cofactor is most directly responsible
for his symptoms?
A. Pyridoxine
B. Biotin
C. Thiamine pyrophosphate
D. Tetrahydrofolate
Correct Answer: 🔴 C. Thiamine pyrophosphate
Explanation: 🔹 Wernicke encephalopathy results from thiamine (vitamin B1)
deficiency, commonly associated with chronic alcoholism. Thiamine pyrophosphate
functions as a cofactor in pyruvate dehydrogenase, α-ketoglutarate dehydrogenase,
and transketolase reactions. Deficiency impairs cerebral energy metabolism,
producing confusion, ophthalmoplegia, and ataxia. Pyridoxine deficiency may cause
neuropathy, biotin deficiency causes dermatitis and alopecia, while folate deficiency
causes megaloblastic anemia.
Q4. A patient with uncontrolled diabetes mellitus develops diabetic ketoacidosis.
Which metabolic pathway is primarily responsible for excessive ketone body
formation?
A. Glycogenesis
B. β-oxidation of fatty acids
C. Pentose phosphate pathway
D. Glycolysis
Correct Answer: 🔴 B. β-oxidation of fatty acids
Explanation: 🔹 In diabetic ketoacidosis, insulin deficiency promotes lipolysis,
releasing free fatty acids that undergo β-oxidation in the liver. Excess acetyl-CoA
generated exceeds Krebs cycle capacity and is diverted toward ketogenesis, forming
acetoacetate and β-hydroxybutyrate. Glycogenesis is impaired in diabetes, glycolysis
is reduced, and the pentose phosphate pathway does not generate ketone bodies.
, Q5. A scientist identifies a mutation causing replacement of glutamic acid with valine
in the β-globin chain. Which structural level of protein organization is directly altered?
A. Primary structure
B. Secondary structure
C. Tertiary structure
D. Quaternary structure
Correct Answer: 🔴 A. Primary structure
Explanation: 🔹 The primary structure of a protein refers to its amino acid sequence.
Sickle cell disease results from substitution of valine for glutamic acid at the sixth
position of the β-globin chain. This altered amino acid sequence changes hemoglobin
behavior under low oxygen conditions. Secondary structure involves α-helices and β-
sheets, tertiary structure concerns 3D folding, and quaternary structure refers to
interactions between protein subunits.
Q6. A patient develops severe muscle cramps after intense exercise. Laboratory studies
reveal elevated lactate levels. Deficiency of which enzyme most likely contributes to
this condition?
A. Glucose-6-phosphatase
B. Pyruvate dehydrogenase
C. Glycogen phosphorylase
D. Fructokinase
Correct Answer: 🔴 C. Glycogen phosphorylase
Explanation: 🔹 McArdle disease results from skeletal muscle glycogen phosphorylase
deficiency, impairing glycogen breakdown during exercise. Patients experience
muscle cramps, fatigue, and myoglobinuria with elevated lactate abnormalities.
Glucose-6-phosphatase deficiency causes Von Gierke disease, pyruvate
dehydrogenase deficiency causes neurologic deficits and lactic acidosis, while
fructokinase deficiency is generally benign.
(COMSAE) PHASE 1 FORM 111 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 111
2026/2027 EDITION
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
COMPLETE PRACTICE EXAM
100 MULTIPLE-CHOICE QUESTIONS
EXACT OFFICIAL COUNT: 100 QUESTIONS
PASSING SCORE: 70%
TESTING TIME: 120 MINUTES
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
NBOME BLUEPRINT-ALIGNED COMPREHENSIVE PRACTICE EXAMINATION ||
OSTEOPATHIC PRINCIPLES & CLINICAL SCIENCES || INTEGRATED BASIC AND CLINICAL
MEDICINE REVIEW || PROFESSIONAL BOARD PREPARATION RESOURCE || 100%
ORIGINAL VERIFIED PRACTICE CONTENT || COMPREHENSIVE MEDICAL ASSESSMENT
PREPARATION || DESIGNED FOR COMLEX-USA LEVEL 1 READINESS || PROFESSIONAL
EXAMINATION USE ONLY
━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Questions 1–10 — Biochemistry & Molecular Medicine
Q1. A 6-month-old infant presents with seizures, developmental delay, and a musty
body odor. Laboratory testing demonstrates elevated phenylalanine levels. The patient
was born after an uncomplicated pregnancy and was exclusively breastfed. Which of
the following best explains the pathophysiology underlying this condition?
,A. Deficiency of homogentisate oxidase resulting in connective tissue deposition
B. Impaired conversion of phenylalanine to tyrosine due to tetrahydrobiopterin-related
dysfunction
C. Defective branched-chain α-ketoacid dehydrogenase complex activity
D. Inability to transport neutral amino acids across intestinal epithelial cells
Correct Answer: 🔴 B. Impaired conversion of phenylalanine to tyrosine due to
tetrahydrobiopterin-related dysfunction
Explanation: 🔹 Phenylketonuria (PKU) results from deficient phenylalanine
hydroxylase activity or defects in tetrahydrobiopterin (BH4), a required cofactor.
Accumulation of phenylalanine leads to neurotoxicity, developmental delay, seizures,
eczema, and a characteristic musty odor. Choice A describes alkaptonuria, Choice C
refers to maple syrup urine disease, and Choice D describes Hartnup disease. Early
diagnosis through newborn screening prevents severe neurologic complications
through dietary restriction of phenylalanine.
Q2. A researcher is studying an enzyme involved in glycolysis. She observes that
increasing substrate concentration beyond a certain point fails to increase reaction
velocity. Which parameter has most likely been reached?
A. Km
B. Ki
C. Vmax
D. Ka
Correct Answer: 🔴 C. Vmax
Explanation: 🔹 Vmax represents the maximum reaction velocity achieved when all
enzyme active sites are saturated with substrate. Beyond this point, increasing
substrate concentration cannot further accelerate the reaction. Km reflects substrate
affinity, Ki is the inhibition constant, and Ka relates to acid dissociation. This
principle is fundamental in understanding enzyme kinetics and pharmacologic
interactions.
,Q3. A 45-year-old man with chronic alcoholism presents with confusion,
ophthalmoplegia, and ataxia. Deficiency of which cofactor is most directly responsible
for his symptoms?
A. Pyridoxine
B. Biotin
C. Thiamine pyrophosphate
D. Tetrahydrofolate
Correct Answer: 🔴 C. Thiamine pyrophosphate
Explanation: 🔹 Wernicke encephalopathy results from thiamine (vitamin B1)
deficiency, commonly associated with chronic alcoholism. Thiamine pyrophosphate
functions as a cofactor in pyruvate dehydrogenase, α-ketoglutarate dehydrogenase,
and transketolase reactions. Deficiency impairs cerebral energy metabolism,
producing confusion, ophthalmoplegia, and ataxia. Pyridoxine deficiency may cause
neuropathy, biotin deficiency causes dermatitis and alopecia, while folate deficiency
causes megaloblastic anemia.
Q4. A patient with uncontrolled diabetes mellitus develops diabetic ketoacidosis.
Which metabolic pathway is primarily responsible for excessive ketone body
formation?
A. Glycogenesis
B. β-oxidation of fatty acids
C. Pentose phosphate pathway
D. Glycolysis
Correct Answer: 🔴 B. β-oxidation of fatty acids
Explanation: 🔹 In diabetic ketoacidosis, insulin deficiency promotes lipolysis,
releasing free fatty acids that undergo β-oxidation in the liver. Excess acetyl-CoA
generated exceeds Krebs cycle capacity and is diverted toward ketogenesis, forming
acetoacetate and β-hydroxybutyrate. Glycogenesis is impaired in diabetes, glycolysis
is reduced, and the pentose phosphate pathway does not generate ketone bodies.
, Q5. A scientist identifies a mutation causing replacement of glutamic acid with valine
in the β-globin chain. Which structural level of protein organization is directly altered?
A. Primary structure
B. Secondary structure
C. Tertiary structure
D. Quaternary structure
Correct Answer: 🔴 A. Primary structure
Explanation: 🔹 The primary structure of a protein refers to its amino acid sequence.
Sickle cell disease results from substitution of valine for glutamic acid at the sixth
position of the β-globin chain. This altered amino acid sequence changes hemoglobin
behavior under low oxygen conditions. Secondary structure involves α-helices and β-
sheets, tertiary structure concerns 3D folding, and quaternary structure refers to
interactions between protein subunits.
Q6. A patient develops severe muscle cramps after intense exercise. Laboratory studies
reveal elevated lactate levels. Deficiency of which enzyme most likely contributes to
this condition?
A. Glucose-6-phosphatase
B. Pyruvate dehydrogenase
C. Glycogen phosphorylase
D. Fructokinase
Correct Answer: 🔴 C. Glycogen phosphorylase
Explanation: 🔹 McArdle disease results from skeletal muscle glycogen phosphorylase
deficiency, impairing glycogen breakdown during exercise. Patients experience
muscle cramps, fatigue, and myoglobinuria with elevated lactate abnormalities.
Glucose-6-phosphatase deficiency causes Von Gierke disease, pyruvate
dehydrogenase deficiency causes neurologic deficits and lactic acidosis, while
fructokinase deficiency is generally benign.
