Deck 3: Biochemistry

Question 1

A 2-year-old boy is evaluated for easy bruising.  His parents report that he develops marked bruising and open wounds following minor trauma.  The skin is difficult to suture due to its extreme fragility.  Physical examination reveals hyperextensible skin, multiple ecchymoses over the forearms and pretibial regions, and an umbilical hernia.  A skin biopsy is performed, and histochemical evaluation of the biopsy reveals a defect in extracellular processing of collagen.  Which of the following steps of collagen synthesis is most likely impaired in this patient?

A)Glycosylation of hydroxylysine residues
B)Interchain C-terminal disulfide bond formation
C)N-terminal propeptide removal
D)Proline residue hydroxylation
E)Triple helix formation

Answer 1

C

This child likely has Ehlers-Danlos syndrome, a group of rare hereditary disorders characterized by defective collagen synthesis.  The condition can be caused by a deficiency in procollagen peptidase, the enzyme that cleaves terminal propeptides from procollagen in the extracellular space.  Impaired propeptide removal results in the formation of soluble collagen that does not properly crosslink.  Consequently, patients often have joint laxity, hyperextensible skin, fragile tissue with easy bruising, and poor wound healing.
Each collagen molecule consists of 3 polypeptide α-chains held together by hydrogen bonds, forming a triple helix.  Collagen assumes this conformation because each of the α-chains has a simple, repetitive amino acid sequence represented as (Gly-X-Y)_n.  The smallest amino acid, glycine (Gly), is necessary at every third position to ensure compact coiling of the helix.  Many of the amino acids represented by X and Y are proline residues, which kink the polypeptide chain and enhance the rigidity of the helical structure due to their ring configuration.
Mature collagen is synthesized by fibroblasts, osteoblasts, and chondroblasts through the following steps:
As translation begins in the cytoplasm, an amino acid signal sequence at the N-terminus of the α-chain facilitates ribosomal binding to the rough endoplasmic reticulum (RER) and passage of the growing polypeptide chain (pre-pro-α-chain) into the RER.
Inside the RER, the hydrophobic signal sequence is cleaved to yield the pro-α-chain.  Proline and lysine at the Y positions of the pro-α-chain are hydroxylated to hydroxyproline and hydroxylysine, respectively (Choice D).  Glycosylation of select hydroxylysine residues also occurs within the RER (Choice A).
The central helical region of the pro-α-chain is flanked by N- and C-terminal propeptides.  Disulfide bond formation between the C-terminal propeptide region of 3 α-chains brings the chains into an alignment favorable for assembly into a triple helix (procollagen molecule) (Choices B and E).
Procollagen molecules are then transported through the Golgi apparatus into the extracellular space.  The N- and C-terminal propeptides are cleaved by procollagen peptidases, converting procollagen into less soluble tropocollagen.
Tropocollagen monomers self-assemble into collagen fibrils.  Finally, lysyl oxidase helps create covalent crosslinks between collagen fibrils to form strong collagen fibers.
Educational objective:
Ehlers-Danlos syndrome is a group of rare hereditary disorders characterized by defective collagen synthesis.  It can be caused by procollagen peptidase deficiency, which results in impaired cleavage of terminal propeptides in the extracellular space.  Patients often have joint laxity, hyperextensible skin, and tissue fragility due to the formation of soluble collagen that does not properly crosslink.
__________
References:
Defect in conversion of procollagen to collagen in a form of Ehlers-Danlos syndrome.
(http://www.ncbi.nlm.nih.gov/pubmed/4742738)
Defects in the biochemistry of collagen in diseases of connective tissue.
(http://www.ncbi.nlm.nih.gov/pubmed/1448)
Clinical and genetic aspects of Ehlers-Danlos syndrome, classic type.
(http://www.ncbi.nlm.nih.gov/pubmed/20847697)

Question 2

Foreign antigen recognition at the cell surface by cytotoxic T-lymphocytes stimulates a response that results in rapid cell death.  Which of the following act as effectors of this response?

A)Matrix metalloproteinases
B)Acid hydrolases
C)Caspases
D)Phospholipase A₂
E)Protein kinase A

Answer 2

C
The two primary modes of cell death are necrosis (which is induced by injury) and apoptosis (which is initiated by the host organism in response to cell damage, age-related atrophy, or specific stages of embryogenesis).  Apoptosis is helpful in the elimination of cells that are no longer necessary and in the maintenance of a constant number of cells in rapidly growing tissues.  Tumor cells, for example, die by apoptosis.  The death of B and T lymphocytes and virally-infected cells also occurs through apoptosis.  The remains of cells that die by this method are phagocytized by macrophages.
The process of apoptosis involves the following steps:
(Choice A) Metalloproteinases are zinc-containing enzymes that degrade the components of the extracellular matrix (eg, collagen, laminin, fibronectin).  Metalloproteinases are essential for proper tissue remodeling during wound healing.
(Choice B) Acid hydrolases do not participate in apoptosis.
(Choice D) Phospholipase A₂ does not participate in apoptosis.
(Choice E) Protein kinase A is a component of the cAMP-associated signaling system.  The binding of a ligand to a G-protein-linked receptor results in adenylyl cyclase activation and the release of cAMP.  Elevated levels of cAMP activate protein kinase A.
Educational Objective:
Apoptosis can occur through either the intrinsic (mitochondria-mediated) pathway or the extrinsic (receptor-initiated) pathway.  Both pathways converge in the activation of caspases.  Caspases are proteolytic enzymes that cleave cellular proteins.

Question 3

A 6-month-old boy is brought to the emergency department by his mother because of recent onset of vomiting, irritability, and jaundice.  The infant was born at term and had been healthy until the onset of these symptoms.  All of his vaccinations are up-to-date.  He had been breast-fed exclusively until 1 week ago, when cereals and fruit juices were introduced into his diet.  Further evaluation reveals hepatomegaly and abnormal liver function tests.  Which of the following enzymes is most likely to be deficient in this patient?

A)Galactose-1-phosphate uridyl transferase
B)Aldolase B
C)Fructokinase
D)Galactokinase
E)Acid α-glucosidase

Answer 3

B
Dietary fructose is obtained mainly from fruits, vegetables, honey, table sugar (sucrose), and processed foods.  Fructose is rapidly absorbed in the proximal small bowel by the hexose transporter GLUT 5.  Initial metabolism of fructose involves three enzymes: fructokinase, aldolase B, and triokinase.  Fructose is phosphorylated on the first carbon by hepatic fructokinase, yielding fructose-1-phosphate.  Metabolism of fructose-1-phosphate by aldolase B generates dihydroxyacetone phosphate (DHAP) and glyceraldehyde.  Glyceraldehyde is then phosphorylated to glyceraldehyde-3-phosphate (G3P), an intermediate of glycolysis, by triose kinase.  DHAP can also be converted to G3P by triose phosphate isomerase.
Aldolase B deficiency causes the potentially life-threatening disorder known as hereditary fructose intolerance.  Patients typically present when fructose-containing foods are introduced into the diet.  The primary manifestations are vomiting and hypoglycemia about 20-30 minutes after fructose ingestion.  Hypoglycemia results from intracellular accumulation of fructose-1-phosphate and depletion of inorganic phosphate, which inhibit glycogenolysis and gluconeogenesis.  Failure to thrive, hepatomegaly, and jaundice can also occur.  Undiagnosed individuals may eventually develop liver and renal failure.  Elimination of dietary fructose is the mainstay of treatment and results in symptom improvement with a good long-term prognosis.
(Choices A and D)  Galactose-1-phosphate uridyl transferase deficiency (classic galactosemia) is an autosomal recessive disorder characterized by vomiting, feeding intolerance, neonatal jaundice, hepatomegaly, and death if untreated.  Symptoms start soon after breastfeeding is initiated.  Galactokinase deficiency is a more benign disorder of galactose metabolism that results in the formation of neonatal cataracts.
(Choice C)  Fructokinase deficiency causes essential fructosuria, a benign autosomal recessive disorder.  Fructose from the diet is absorbed and secreted freely in the urine due to impairment of the first step in fructose metabolism.
(Choice E)  Glycogenolysis is accomplished mainly by glycogen phosphorylase and debranching enzyme, but a small amount is also broken down by the lysosomal enzyme α-1,4-glucosidase.  Alpha-glucosidase (or acid maltase) deficiency causes Pompe disease.  This disease presents not with hypoglycemia, but with cardiomyopathy and hypotonia.
Educational objective:
Aldolase B deficiency causes hereditary fructose intolerance.  This disease manifests after introduction of fructose into the diet with vomiting and hypoglycemia about 20-30 minutes after fructose ingestion.  These infants can present with failure to thrive, jaundice, and hepatomegaly.

Question 4

Succinate dehydrogenase (SDH) is an enzyme complex located within the inner mitochondrial membrane that catalyzes the oxidation of succinate to fumarate.  An experiment is conducted to determine if malate alters the rate of SDH activity.  Reaction velocity is measured with and without a fixed quantity of malate as succinate concentration is gradually increased.  Obtained results are shown below. Which of the following is the most accurate statement about malate in this experiment?

A)It alters the maximal velocity of the reaction
B)It binds the enzyme at a different site than succinate
C)It covalently binds the enzyme
D)It decreases affinity of the enzyme for succinate
E)It is a competitive inhibitor of the enzyme

Question 5

A 54-year-old man comes to the emergency department with a 3-month history of fatigue and exertional dyspnea.  He has early satiety and frequent upper abdominal discomfort.  On physical examination, the patient has palpable splenomegaly but no lymphadenopathy.  Laboratory tests are as follows: Reverse transcription polymerase chain reaction is used to diagnose chronic myelogenous leukemia in this patient.  Which of the following is most likely to be detected by this test?

A)Chromosomal position of the BCR and ABL genes
B)DNA rearrangement in the BCR promoter region
C)Fusion protein containing BCR and ABL domains
D)Messenger RNA transcript containing BCR and ABL exons
E)Point mutation in the ABL enhancer region

Question 6

A 5-year-old girl is brought to the clinic due to several months of fatigue and difficulty walking.  She ambulates normally at first but rapidly becomes weak and tired.  The patient has not been ill recently and is usually happy and playful.  She has a history of mild motor delays but is otherwise developmentally normal.  Vital signs are within normal limits.  Examination shows mildly decreased power in all extremities but no ataxia.  Cardiac auscultation reveals a 1/6 systolic murmur and an S3 gallop.  Laboratory results are as follows: Muscle biopsy shows a very low carnitine content.  This patient most likely has deficient synthesis of which of the following substances?

A)Acetoacetate
B)Arachidonic acid
C)Glutathione
D)Homocysteine
E)Lactate
F)Palmitate

Question 7

A 6-month-old full-term boy is brought to the emergency department with lethargy and vomiting.  He was born by uncomplicated spontaneous vaginal delivery and has been growing and developing normally.  The patient was breastfed exclusively until 2 days ago when homemade pureed food was added to his diet.  He has had no fever or diarrhea.  His parents are healthy and he has had no sick contacts.  Examination shows a pale, diaphoretic, and ill-appearing infant.  Serum glucose is 30 mg/dL.  Diagnostic testing confirms aldolase B deficiency.  Which of the following should be removed from this patient's diet?

A)Amylose
B)Cellulose
C)Galactose
D)Glucose
E)Lactose
F)Maltose
G)Sucrose

Question 8

A 5-day-old term newborn is brought to the emergency department for multiple episodes of emesis.  The breastfed infant has been having fewer wet diapers over the last 2 days.  Vital signs show tachycardia, tachypnea, and hypotension.  Physical examination shows an icteric, lethargic baby with a sunken fontanelle, dry mucous membranes, and hepatomegaly.  A blood culture is drawn and empiric antibiotics are initiated.  Hematologic studies show leukocytosis with bandemia.  Serum studies show hypoglycemia and elevated transaminases.  The ammonia level is normal.  Newborn screen is pending.  Preliminary results from arterial blood culture show gram-negative rods.  The infant is placed on a special formula and gradually improves over the next few days.  Which of the following steps in metabolism is most likely impaired in this patient?

A)A
B)B
C)C
D)D
E)E

Question 9

A 68-year-old man comes to the office due to an enlarging mole on his right forearm.  The patient is a retired farmer and received a significant amount of sun exposure over the course of his life.  On examination, he has a black-brown macular lesion on the dorsum of his right forearm measuring approximately 1 cm in diameter with an irregular border.  Excisional biopsy is performed and histopathology reveals malignant melanoma.  Immunohistochemical analysis indicates that the malignant cells have decreased integrin expression.  These cells are most likely to exhibit poor adhesion to which of the following components of the extracellular matrix?

A)Actin
B)Fibronectin
C)Hyaluronic acid
D)Keratan sulfate
E)Keratin

Question 10

An 8-year-old boy is brought to the emergency department due to vomiting and lethargy.  The patient had been on an overnight hiking trip with his family.  During the trip, the family lost their food pack while canoeing and had to hike back to their car.  The child became weak and was carried for the last mile.  None of the family has eaten for approximately 24 hours.  On examination, the patient appears listless.  Mild hepatomegaly is noted.  Laboratory results are as follows: The patient begins seizing shortly after arriving at the emergency department.  Which of the following enzymes is most likely deficient in this patient?

A)Acetyl-CoA carboxylase
B)Acid alpha-glucosidase
C)Acyl-CoA dehydrogenase
D)Glucose 6-phosphatase
E)Glycogen phosphorylase

Question 11

An 11-year-old girl is evaluated for blurry vision.  The patient was adopted internationally at age 9.  She has no history of head or eye trauma or exposure to ionizing radiation.  Motor and cognitive milestones have been achieved at the appropriate age.  She has a good appetite and does not follow any specific diet.  The patient takes no medications and has no allergies.  Vaccinations are up to date.  Vital signs are normal.  She is at the 40th percentile for height and weight.  Other than bilateral lens opacities, the rest of her examination is normal.  Urine is positive for reducing substances.  Deficient activity of which of the following enzymes is the most likely cause of this patient's eye condition?

A)Aldolase B
B)Alpha-galactosidase A
C)Fructokinase
D)Galactokinase
E)Glucose-6-phosphatase
F)Hexosaminidase A
G)Sphingomyelinase

Question 12

A 24-year-old woman comes to the office for a preemployment medical evaluation.  The patient has no known medical problems but reports that her skin bruises and scars easily.  She says that most of her family members have a very "flexible" body, and her brother works in a circus as a contortionist.  The patient takes no medications and has no allergies.  She does not use tobacco, alcohol, or drugs.  Physical examination findings are shown in the exhibit. 


This patient most likely has an inherited defect in which of the following proteins?

A)Collagen
B)Elastin
C)Fibrillin-1
D)Hyaluronic acid
E)Laminin
F)Proteoglycan

Question 13

Two graphs illustrating the transport rate of solutes across the plasma membrane are shown on the slide below. Which of the following best explains the difference in the shape of the curves?

A)Different amounts of membrane surface area for diffusion
B)Different degrees of membrane thickness
C)The 2 solutes have different molecular weights
D)The 2 solutes have different oil/water partition coefficients
E)The presence of a protein transporter

Question 14

A 54-year-old woman is evaluated for progressive constipation, anorexia, and a 5.4-kg (12-lb) weight loss over the past several months.  Physical examination is unremarkable.  Stool guaiac test is positive, and a colonoscopy is performed.  An exophytic mass is identified in the sigmoid colon.  The patient undergoes a left hemicolectomy, and histopathology of the surgical specimen is positive for adenocarcinoma.  Molecular testing of the cancer cells reveals a mutation in the KRAS gene that results in constitutive activation of the Ras protein.  Under normal circumstances, this protein is only active when bound to which of the following substances?

A)ATP
B)Ca²⁺
C)cAMP
D)GTP
E)IP₃

Question 15

A 20-year-old man is evaluated in the emergency department for weakness, malaise, and dark urine.  The patient was treated for a bacterial skin infection several days ago.  Physical examination shows scleral icterus.  Laboratory results reveal anemia with an elevated reticulocyte count.  Abnormal erythrocytes are seen on peripheral smear.  Which of the following substrate flow pathways is most likely deficient in this patient?

A)A
B)B
C)C
D)D
E)E
F)F
G)G

Question 16

Nutrition researchers investigating the relationship between fructose consumption and cardiovascular disease conduct a prospective cohort study on a population of randomly selected young adults.  Study participants undergo semiannual measurement of waist circumference, blood pressure, and serum cholesterol and triglyceride concentrations.  Dietary fructose consumption is assessed through the use of questionnaires and by measuring urinary fructose excretion.  A 23-year-old man enrolled in the study is found to excrete large amounts of fructose in his urine compared to other study participants despite maintaining a moderate fructose intake.  Further evaluation shows a hereditary defect in fructose metabolism, but he is asymptomatic and has no other medical problems.  This patient most likely remains able to metabolize fructose due to the compensatory activity of which of the following enzymes?

A)Aldolase B
B)Aldose reductase
C)Fructokinase
D)Hexokinase
E)UDP-galactose-4-epimerase

Question 17

A 23-year-old apparently healthy man who recently immigrated to the United States comes to an outpatient clinic to establish care.  When asked about his past medical history, he says that he has no significant medical problems.  However, his mother told him that he was born with "a problem metabolizing sugar."  The patient maintains no dietary restrictions and regularly eats vegetables, fruits, meats, and processed foods.  Urine samples show a repeatedly positive copper reduction test, but glucose oxidase dipstick testing is negative.  Which of the following enzymes is most likely to be deficient in this patient?

A)Acid α-glucosidase
B)Aldolase B
C)Fructokinase
D)Galactose-1-phosphate uridyl transferase
E)Lactase

Question 18

A research scientist studying the metabolic pathways that contribute to obesity feeds experimental animals a high-carbohydrate, high-protein diet for a prolonged period.  A sample of liver tissue is then obtained from the animals, and the activity of various enzymes involved in fatty acid metabolism is measured and recorded.  It is determined that beta-oxidation of fatty acids is inhibited within these cells as a result of the diet.  An increase in which of the following substances is most likely responsible for the observed effect?

A)Acetoacetate
B)Carnitine
C)Citrate
D)Malonyl-CoA
E)NADPH

Question 19

Biochemists working for a national endocrinology institute are investigating the specifics underlying glucose transport across adipose cell membranes.  One of their experiments shows that, in the presence of insulin, D-glucose transport across the plasma membrane of adipocytes is much faster than L-glucose transport.  Which of the following transport processes best describes the mechanism for glucose entry into these cells?

A)Simple diffusion
B)Receptor-mediated endocytosis
C)Carrier-mediated transport
D)Primary active transport
E)Co-transport

Question 20

Erythroblasts isolated from a bone marrow biopsy sample of a patient with neonatal jaundice are incubated in a medium containing radiolabeled glucose.  The cells are unable to generate NADPH from glucose metabolism but are able to convert fructose-6-phosphate to ribose-5-phosphate, which is required for nucleic acid synthesis.  Which of the following enzymes is essential for the latter conversion?

A)Aconitase
B)Enolase
C)Glucose-6-phosphate dehydrogenase
D)Glutathione reductase
E)Transketolase

Question 21

A 64-year-old man comes to the emergency department due to severe abdominal pain, nausea, and vomiting.  He has a history of hypertension, myocardial infarction, and systolic heart failure.  His blood pressure is 100/60 mm Hg, pulse is 116/min and irregular, and respirations are 24/min.  Examination shows a soft, mildly distended, and tender abdomen.  Laboratory results are as follows: CT scan of the abdomen reveals distal ileal wall thickening and lack of enhancement with intravenous contrast.  Decreased activity of which of the following enzymes best explains the acid-base disorder in this patient?

A)Enolase
B)Lactate dehydrogenase
C)Pyruvate carboxylase
D)Pyruvate dehydrogenase
E)Pyruvate kinase

Question 22

A 9-month-old boy is brought to the clinic for a routine follow-up.  His mother is concerned because the patient is not yet able to sit up unsupported.  He was born at term and has had muscle weakness since birth.  Vital signs are normal.  The patient is alert but has diminished tone.  Examination shows a prominent forehead with a depressed nasal bridge.  Eye examination shows epicanthal folds.  Analysis of lysosomal acid hydrolases shows an increased concentration within the serum and a decreased level within the cultured skin fibroblast cells.  This patient most likely has a defect in which of the following steps of enzyme production?

A)DNA methylation
B)Posttranslational modification
C)Protein folding
D)Splicing
E)Translation

Question 23

A 5-month-old boy is brought to the office due to poor feeding.  His mother says that he has difficulty holding his head up while breastfeeding and his suckling seems weaker than usual.  Weight is at the 5th percentile.  Length and head circumference are tracking along the 25th percentile.  Physical examination shows hepatomegaly and hypotonia in all 4 limbs.  Cardiac auscultation shows a gallop rhythm, and chest x-ray reveals severe cardiomegaly.  Muscle biopsy shows enlarged lysosomes containing periodic acid-Schiff (PAS)-positive material.  Which of the following enzymes is most likely deficient in this patient?

A)Acid alpha-glucosidase
B)Galactokinase
C)Glucose-6-phosphatase
D)Glycogen debrancher enzyme
E)Glycogen phosphorylase
F)Pyruvate kinase

Question 24

A 14-year-old boy is brought to the emergency department after accidental ingestion of a chicken bone that lodged in his esophagus.  Upper endoscopy is performed and the bone is successfully removed.  However, the patient is incidentally found to have mild hypercalcemia on laboratory testing.  On follow-up with his primary care provider 2 weeks later, he has no symptoms and clinical examination is unremarkable.  Further questioning reveals that several of his family members also have mild hypercalcemia.  Subsequent laboratory studies show a borderline high parathyroid hormone concentration, very low urinary calcium level, and normal 25-hydroxyvitamin D level.  A mutation in which of the following receptors is most likely responsible for this patient's laboratory abnormalities?

A)Intracellular receptor with a DNA-binding domain
B)Membrane-bound receptor coupled with a G protein
C)Transmembrane ligand-gated ion channel
D)Transmembrane receptor associated with intrinsic tyrosine kinase activity
E)Transmembrane receptor causing activation of Janus kinase/STAT pathway

Question 25

An autopsy is being performed on a 4-year-old boy who recently died from a myocardial infarction.  The child had a history of intellectual disability.  Autopsy shows a prominent forehead and broad nose.  There is a diffuse haze over the corneas bilaterally.  The heart, liver, and spleen are enlarged.  Sampling of the coronary arteries is most likely to reveal intimal accumulation of which of the following substances?

A)Cholesterol
B)Glucocerebroside
C)Glycogen
D)Heparan sulfate
E)Sphingomyelin

Question 26

A 35-year-old woman comes to the emergency department with nausea, vomiting, and fever.  Her symptoms began 24 hours ago, and she has been unable to eat or drink anything since.  She has a 3-year-old daughter who had similar symptoms 2 days earlier but is now fine.  Laboratory studies show a blood glucose level of 82 mg/dL despite her 24-hour fast.  Maintenance of this patient's blood glucose levels is facilitated by hepatic conversion of pyruvate into glucose.  Which of the following substances directly stimulates the first enzyme involved in this process?

A)Acetyl-CoA
B)Alanine
C)Citrate
D)Fructose 2,6-bisphosphate
E)Lactate
F)Oxaloacetate

Question 27

A 12-year-old boy is brought to the emergency department with severe chest pain.  He has had intermittent substernal chest pain for the past few months that typically occurs after heavy activity.  The boy's activities have been limited due to the chest pain, and he is no longer able to play on the soccer team.  The patient does not use tobacco or illicit drugs.  His temperature is 36.7 C (98 F), blood pressure is 130/80 mm Hg, pulse is 132/min, respirations are 24/min, and pulse oximetry is 98% on room air.  BMI is 17 kg/m².  Physical examination shows an anxious-appearing boy with a rapid but regular pulse.  No abnormalities are seen.  Troponin is elevated, and ECG reveals ST segment elevations in leads II, III, and aVF.  After acute stabilization and treatment, further laboratory workup shows an increased serum methionine level.  Which of the following amino acids is most likely essential in this patient?

A)Asparagine
B)Cysteine
C)Isoleucine
D)Leucine
E)Tyrosine
F)Valine

Question 28

A 34-year-old previously healthy man comes to the emergency department due to a 3-hour history of chest pain, diaphoresis, and dyspnea.  He does not smoke, exercises regularly, and eats a balanced diet.  His father died at age 56 from a myocardial infarction.  His blood pressure is 110/70 mm Hg and pulse is 110/min and regular.  Physical examination is unremarkable.  ECG shows ST elevation in the anterolateral leads.  Coronary angiogram reveals proximal left anterior descending artery stenosis and thrombosis, which is treated with angioplasty and stent placement.  Laboratory results are as follows: Further testing reveals a homozygous mutation in the methylene tetrahydrofolate reductase gene that leads to decreased enzymatic activity.  Due to this defect, the patient most likely has impairment converting homocysteine to which of the following?

A)Cystathionine
B)Cysteine
C)Methionine
D)Methylmalonyl-CoA
E)Succinyl-CoA

Question 29

Researchers lyse human cells and isolate a specific messenger RNA template using gel electrophoresis.  Reverse transcription polymerase chain reaction is then used to synthesize complementary DNA (cDNA) from the RNA template.  Next, the cDNA is modified into an expression vector containing an optimized bacterial promoter, ribosomal binding site, and terminator sequence.  After insertion of the vector into appropriate bacterial hosts, the transformed bacteria are cultured in a bioreactor and produce large quantities of a protein containing a domain that binds to a specific DNA sequence.  This protein is most likely the receptor for which of the following hormones?

A)Glucagon
B)Growth hormone
C)Insulin
D)Insulin-like growth factor
E)Parathyroid hormone
F)Progesterone

Question 30

An 8-year-old boy is evaluated for exercise intolerance.  The patient experiences fatigue, muscle pain, and cramps during exercise as well as severe muscle stiffness following strenuous activity.  Physical examination is unremarkable.  A forearm ischemic exercise test is performed by applying a blood pressure cuff on the patient's exercising forearm and sampling blood lactate several minutes after the exercise.  The patient's blood samples show no rise in lactate levels.  Biochemical analysis of a muscle biopsy reveals absent lactate dehydrogenase activity.  In this patient, strenuous exercise leads to inhibition of glycolysis in skeletal muscle due to intracellular depletion of which of the following substances?

A)AMP
B)Carnitine
C)Citrate
D)FADH₂
E)NAD⁺
F)Pyruvate

Question 31

A 69-year-old woman with Alzheimer disease is brought to the emergency department after getting lost while taking a walk in her neighborhood.  Her son has been unable to contact the patient for the last 2 days, and today the police found her wandering in a park.  The patient says that she drank water from a park fountain but has not had anything to eat for over 24 hours.  On physical examination, she is mildly confused with dry mucous membranes.  Laboratory studies show a blood glucose level of 92 mg/dL.  Which of the following hormones binds to an intracellular receptor to help maintain this patient's laboratory findings within the normal range?

A)Cortisol
B)Epinephrine
C)Glucagon
D)Growth hormone
E)Insulin
F)Norepinephrine

Question 32

A 2-year-old boy is being evaluated at the office for failure to thrive and developmental delay.  Medical history is significant for recurrent ear infections since 6 months of age.  Physical examination shows corneal clouding, hepatosplenomegaly, and restricted joint mobility.  Further evaluation shows deficient phosphorylation of mannose residues on certain glycoproteins in the Golgi apparatus.  In unaffected patients, these proteins are normally transported to which of the following cellular locations?

A)Endoplasmic reticulum
B)Extracellular space
C)Lysosome
D)Mitochondria
E)Plasma membrane

Question 33

A 35-year-old man comes to the office with progressively worsening fatigue associated with dark urine and back pain.  Two days ago, the patient ate some large, flat beans brought home by his wife after a business trip to Egypt.  Physical examination shows jaundice and pallor.  Laboratory results reveal a hemoglobin level of 8 g/dL.  Further evaluation reveals deficiency of an enzyme involved in the conversion of glucose-6-phosphate to ribulose-5-phosphate.  The substance generated during this conversion is necessary for which of the following biochemical processes?

A)ADP phosphorylation
B)Fatty acid synthesis
C)Glycogen storage
D)Ketone body synthesis
E)Protein degradation

Question 34

Researchers analyzing eukaryotic genome structure and function perform an experiment to extract DNA from exocrine pancreatic cells.  During the purification process, they isolate small circular DNA molecules that resemble a bacterial chromosome.  Further analysis shows that these molecules code for proteins, transfer RNA, and ribosomal RNA.  From which of the following cellular structures did these DNA molecules most likely originate?

A)A
B)B
C)C
D)D
E)E

Question 35

A 15-year-old boy is brought to the clinic due to poor exercise endurance.  He recently began weight lifting with friends but has had difficulty performing the exercises.  The patient states that his arms "feel like jelly after just a few repetitions."  He also has severe muscle cramping and has noticed occasional urine discoloration after training sessions.  Further evaluation reveals that the patient's exercise tolerance can be greatly improved by drinking an oral glucose solution before beginning a strenuous activity.  Vital signs are normal, and examination is unremarkable.  This patient is most likely deficient in an enzyme that catalyzes which of the following conversions?

A)A
B)B
C)C
D)D
E)E

Question 36

A 52-year-old man is being evaluated in the emergency department for abdominal pain associated with watery diarrhea.  His symptoms have been progressive over the last month.  He says that he is depressed and often has difficulty remembering things.  The patient has a 20-year history of alcohol use disorder.  On examination, he appears disheveled.  A pigmented scaly skin rash is present in the malar distribution of his face, neck, and back of his hands.  The rash has been present for several months and worsens on exposure to sunlight.  It is determined that the patient's symptoms are secondary to lack of a specific nutrient.  Activity of which of the following enzymes is most likely decreased in the patient as a result of this deficiency?

A)Citrate synthase
B)Hexokinase
C)Isocitrate dehydrogenase
D)Phosphoglycerate kinase
E)Succinate dehydrogenase

Question 37

A healthy 34-year-old coal mine worker is trapped underground following partial collapse of an access shaft.  Rescue efforts are directed toward clearing the obstructed tunnel, but it takes 2 days to reach him.  While being taken to the surface, the miner tells rescuers that he feels dizzy and weak.  He had an emergency supply of water but has not eaten anything for over 30 hours.  Fingerstick blood glucose concentration is 78 mg/dL.  Which of the following biochemical reactions is most likely responsible for maintaining this patient's current blood glucose levels?

A)Acetoacetyl CoA → 3-hydroxy-3-methylglutaryl-CoA
B)Acetyl CoA → palmitic acid
C)Fructose 6-phosphate → fructose 1,6-bisphosphate
D)Glycogen → glucose-1-phosphate
E)Oxaloacetate → phosphoenolpyruvate

Question 38

A 6-month-old girl is brought to the office by her mother for a checkup appointment.  The mother states, "My baby doesn't seem to be growing much despite feeding as often as my previous children.  I am worried that something is wrong with her."  Physical examination shows hepatomegaly, hypotonia, and height and weight below the 10th percentile.  Laboratory studies show hypoglycemia and ketoacidosis.  A liver biopsy shows hepatic fibrosis without fat accumulation.  Further analysis reveals abundant quantities of a multibranched polysaccharide with abnormally short outer chains within the cytosol of the hepatocytes.  Which of the following enzymes is most likely deficient in this patient?

A)Acid maltase
B)Debranching enzyme
C)Glucose-6-phosphatase
D)Liver glycogen phosphorylase
E)Muscle glycogen phosphorylase
F)Pyruvate kinase

Question 39

A 12-year-old boy is brought to the office due to gait instability and pruritic skin rash for the past several weeks.  His mother reports that he has also been irritable and had loose stools during this time.  The patient's childhood development has been unremarkable except for several episodes of similar skin rash that resolved spontaneously.  Examination shows scaly, erythematous skin lesions in sun-exposed areas and cerebellar ataxia.  Laboratory evaluation shows increased levels of neutral amino acids in the urine.  This patient's symptoms would most likely respond to which of the following supplements?

A)Ascorbate
B)Folic acid
C)Niacin
D)Pyridoxine
E)Riboflavin
F)Thiamine
G)Tocopherol

Question 40

A 27-year-old man is brought to the emergency department due to confusion.  His roommate says that he has been binge drinking for the last 5 days and probably has had very little to eat.  The patient's medical history is significant for alcohol-related seizures 1 year ago.  He had been sober until 2 weeks ago, when he started drinking again.  The patient's past medical history is otherwise unremarkable.  On examination, he responds to voice but does not follow commands.  Fingerstick glucose is 35 mg/dL and urine is strongly positive for ketones.  Suppression of which of the following is the primary cause of this patient's hypoglycemia?

A)Gluconeogenesis
B)Glycogenolysis
C)Insulin clearance
D)Insulin sensitivity
E)Lipolysis

Question 41

Molecular biologists studying signal transduction apply an agent to human cells that activates G-protein- dependent phospholipase C.  Which of the following intracellular substances is most likely to increase immediately after exposure to this agent?

A)Ca²⁺
B)cAMP
C)cGMP
D)Cl^-
E)mRNA
F)NO

Question 42

An 8-month-old boy is evaluated for developmental delay, failure to thrive, and episodic seizures.  Physical examination shows ophthalmoplegia and hypotonia.  Laboratory studies reveal an elevated serum lactate level.  Further histochemical studies show severely reduced pyruvate dehydrogenase enzyme activity in both freshly isolated peripheral blood lymphocytes and cultured fibroblasts.  Increasing which of the following substances in his diet is most likely to help this patient generate energy without further elevating lactate levels?

A)Alanine
B)Asparagine
C)Galactose
D)Glycerol
E)Lysine
F)Serine

Question 43

A 43-year-old man prospecting for gold in Arizona becomes stuck in the desert after his truck breaks down.  He brought a large supply of water with him but only a few granola bars as food.  After 3 days, he is able to flag down a passing vehicle and obtain transportation to the nearest settlement.  During this ordeal, his liver begins to synthesize large quantities of glucose from source molecules such as alanine, lactate, and glycerol.  As part of this process, phosphoenolpyruvate is formed from oxaloacetate in a reaction that requires a specific nucleoside triphosphate as a cofactor.  Which of the following reactions directly synthesizes this cofactor?

A)A
B)B
C)C
D)D
E)E
F)F
G)G
H)H

Question 44

A 31-year-old man comes to the office for a routine checkup.  He has no significant medical problems and does not take any medications.  The patient works as a fitness trainer and lifts weights recreationally.  He has been consuming carbohydrate-rich food prior to his weightlifting sessions and claims that it increases muscle strength.  A literature review shows that the rate of glycogenolysis within myocytes increases several hundredfold during active skeletal muscle contraction.  Which of the following substances is most likely responsible for increasing the reaction rate during active contraction?

A)ATP
B)Ca²⁺
C)cAMP
D)Glucose-6-phosphate
E)Lactate

Question 45

A pharmaceutical researcher is studying a target protein involved in the signal transduction and cellular response to TSH.  The protein is isolated and purified from thyroid follicular cells.  Further analysis reveals that the protein contains multiple alpha-helical regions.  Each of these regions is composed of approximately 20 amino acid residues consisting primarily of valine, alanine, and isoleucine.  This particular region of the protein most likely performs which of the following functions?

A)Anchoring to the cell membrane
B)Binding to an extracellular ligand
C)Binding to intranuclear DNA
D)Interacting with metal ions in transporting proteins
E)Phosphorylating tyrosine residues

Question 46

A 7-day-old neonate born to a 28-year-old woman is brought to the office due to progressive lethargy, vomiting, and poor feeding.  The mother reports an uneventful pregnancy and perinatal course.  She exclusively breastfeeds the infant and has no medical problems in any of her other children.  On examination, the infant is somnolent and dehydrated with decreased muscle tone.  Laboratory studies reveal metabolic acidosis with an elevated anion gap, ketosis, and hypoglycemia.  Further evaluation reveals a markedly elevated propionic acid level due to defective conversion of propionyl-CoA to methylmalonyl-CoA.  This patient is most likely unable to use which of the following amino acids for energy production?

A)Alanine
B)Aspartate
C)Glutamate
D)Lysine
E)Phenylalanine
F)Valine

Question 47

A dermatology researcher is studying the role of different amino acids in wound healing.  She cultures mature dermal fibroblasts in growth media.  After several days, the fibroblasts begin synthesizing polypeptide chains that assemble into triple helical structures, followed by fibrils.  The fibrillar proteins are hydrolyzed and separated into their constituent amino acids via paper chromatography.  Which of the following amino acids is most likely to be found in highest quantity in these proteins?

A)Alanine
B)Cysteine
C)Glycine
D)Leucine
E)Lysine
F)Proline

Question 48

A 4-month-old boy is brought to the office for his first visit since arriving in the United States.  The patient was recently adopted, and his adoptive mother says the boy is tremulous compared to her biological children.  Over the past week, the boy has also had episodes of upward eye deviation and bilateral arm and leg shaking for approximately 2 minutes at a time.  Biological family history is not available.  His temperature is 36.7 C (98.1 F), blood pressure is 90/40 mm Hg, pulse is 120/min, and respirations are 30/min.  Examination shows a fair-skinned infant with blue eyes and a musty body odor.  Which of the following amino acids is most likely essential in this patient?

A)Cysteine
B)Isoleucine
C)Leucine
D)Phenylalanine
E)Tyrosine
F)Valine

Question 49

A 14-month-old boy is evaluated for failure to thrive and developmental delay.  His mother reports that at 12 months he could barely lift his head and had difficulty sitting unsupported.  The toddler has not started babbling or forming words.  He is at the 10th percentile for height and 5th percentile for weight.  Laboratory results are as follows: Urine specimens contain large amounts of orotic acid crystals.  Supplementation with which of the following substances would most likely benefit this patient?

A)Ascorbic acid
B)Folic acid
C)Guanine
D)Iron
E)Pyridoxine
F)Uridine

Question 50

Molecular biologists perform a series of experiments to characterize the electrophysiologic properties of human muscle cells.  The resting membrane potential for an isolated muscle cell is determined to be -70 mV.  The equilibrium potentials for important ions under normal physiologic conditions are as follows:E_Na = + 60 mV
E_K = - 90 mV
E_Cl = - 75 mV
E_Ca = + 125 mV
E_Mg = 0 mVIf physiologic conditions are maintained, which of the following ions would most likely flow out of the cell after opening of their respective ion channels?

A)Magnesium and calcium
B)Magnesium and chloride
C)Potassium and chloride
D)Potassium only
E)Sodium and calcium

Question 51

As part of a research study investigating enzymatic activity in both normal and diseased liver tissue, hepatocytes are isolated from biopsy samples obtained from patients undergoing routine care at a local tertiary referral center.  The cells are homogenized and centrifuged to remove membrane components and organelles.  Following subsequent rounds of centrifugation, the remaining supernatant contains only cytosol and cytosolic proteins.  Activity of which of the following enzymes will most likely be detectable in the supernatant of healthy liver cells?

A)3-Hydroxy-3-methylglutaryl-CoA lyase
B)Ornithine transcarbamylase
C)Pyruvate carboxylase
D)Succinate dehydrogenase
E)Transketolase

Question 52

A 47-year-old homeless man comes to the emergency department due to a "pins-and-needles" sensation in his legs.  He also has painful lesions on his lips and corners of his mouth.  He has had no loss of consciousness, nausea, vomiting, or diplopia.  The patient drinks alcohol heavily on a daily basis and has a history of intravenous heroin use.  On physical examination, he appears unkempt and ill appearing.  Temperature is 36.8 C (98.2 F), blood pressure is 146/90 mm Hg, and pulse is 106/min.  He has glossitis and angular stomatitis.  Abdominal examination reveals hepatomegaly.  Laboratory evaluation shows very low urinary riboflavin excretion.  Activity of which of the following enzymes is most likely directly impaired in this patient?

A)Fumarase
B)Glucose-6-phosphate dehydrogenase
C)HMG-CoA reductase
D)Isocitrate dehydrogenase
E)Malate dehydrogenase
F)Succinate dehydrogenase
G)Succinate thiokinase

Question 53

The resting membrane potential for an isolated muscle cell is -70 mV.  Equilibrium potentials for important ions are given below:E_Na = + 60 mV
E_K = - 80 mV
E_Cl = - 70 mV
E_Ca = + 125 mVWhich of the following most likely forms the resting membrane potential of the cell?

A)High potassium conductance and some sodium conductance
B)High chloride conductance and some sodium conductance
C)High calcium conductance and some chloride conductance
D)High potassium conductance and some chloride conductance
E)High potassium conductance only

Question 54

A 1-day-old boy is diagnosed with hyperphenylalaninemia by newborn screening.  He is placed on a special phenylalanine-restricted diet with tyrosine supplementation.  The parents are extensively counseled on the boy's condition and informed of the necessary dietary restrictions.  They are also instructed to return to his physician for regular follow-up visits.  Several months later, laboratory test results indicate that the infant has a normal serum phenylalanine level.  Careful examination, however, reveals some neurological abnormalities, including axial hypotonia and microcephaly.  Further workup is notable for elevated prolactin, and his physician suspects a cofactor deficiency.  Which of the following enzymes is most likely deficient in this patient?

A)Dihydrobiopterin reductase
B)Dopamine β-hydroxylase
C)Phenylalanine hydroxylase
D)Phenylethanolamine N-methyltransferase
E)Tyrosinase

Question 55

A research scientist develops an agent that specifically blocks the interaction of inositol triphosphate with its intracellular receptor.  A study is then performed in which vascular smooth muscle cells are divided into 2 groups: an experimental group treated with the receptor blocker and an untreated control group.  Both groups are exposed to phenylephrine.  Compared to the control cells, decreased activity of which of the following enzymes is most likely to be observed in the experimental cells?

A)Adenylate cyclase
B)Lipoxygenase
C)Phosphodiesterase
D)Phospholipase C
E)Protein kinase C

Question 56

As part of an experiment, healthy volunteers undergo a 12-hour fast and then drink a solution containing radiolabeled alanine.  Consecutive blood samples are drawn every 15 minutes for the next 3 hours.  Initial blood samples detect the radiolabeled alanine, but analysis of later samples shows that the radiotracer is present in blood primarily in the form of glucose.  Before alanine can be converted to glucose, its amino group is transferred to which of the following?

A)α-Ketoglutarate
B)L-citrulline
C)Malate
D)Citrate
E)Oxaloacetate

Question 57

Biologists investigating the morphologic changes associated with reversible cellular injury perform a procedure on anesthetized mice to assess the effects of transient hepatic ischemia.  During the experiment, they clamp the hepatic artery and obtain liver biopsy samples at varying intervals.  The samples are then examined by electron microscopy.  Cells that are exposed to longer ischemic periods are found to have reduced numbers of ribosomes attached to the endoplasmic reticulum.  This structural change is most likely to impair which of the following cellular functions?

A)ATP production
B)Drug detoxification
C)Synthesis of cell membrane proteins
D)Synthesis of cytosolic proteins
E)Synthesis of steroid hormones

Question 58

A researcher is studying the structure of different hormone receptors.  Receptor proteins are isolated and purified from a homogenized tissue sample.  Detailed structural analysis shows that one of the proteins contains a 30-amino acid motif coordinating a zinc molecule, as shown in the image below. A receptor for which of the following hormones was most likely isolated in this experiment?

A)Adrenocorticotropic hormone
B)Antidiuretic hormone
C)Epinephrine
D)Glucagon
E)Growth hormone
F)Insulin
G)Thyroid hormone

Question 59

A 3-year-old boy who recently immigrated to the United States is brought to the physician by his parents because he has not yet begun to walk or speak.  Assessment of his developmental milestones shows severe intellectual disability.  He dies 6 months later from refractory seizures resulting in respiratory failure.  Autopsy shows pallor of the substantia nigra, locus ceruleus, and vagal nucleus dorsalis.  The underlying condition responsible for this patient's death is most likely caused by a deficiency of which of the following enzymes?

A)Branched-chain ketoacid dehydrogenase
B)Dopamine hydroxylase
C)Homogentisic acid oxidase
D)Phenylalanine hydroxylase
E)Tyrosinase

Question 60

A research scientist is studying biochemical reactions that take place in the liver.  He cultures hepatocytes in a growth media enriched with glutamate labeled with nitrogen isotopes.  After some time, he finds that the nitrogen isotopes are transferred to oxaloacetate, forming aspartate in the process.  Which of the following substances is most likely involved in this reaction?

A)Biotin
B)Folic acid
C)Niacin
D)Pyridoxine
E)Riboflavin
F)Thiamine

Question 61

A 24-year-old woman is admitted to the hospital with a diagnosis of acute appendicitis.  She started having right lower quadrant abdominal pain approximately 30 hours earlier but did not go to the hospital because she thought the pain would subside on its own.  The patient had no food, only sips of water, during that time.  Blood pressure is 115/72 mm Hg and pulse is 106/min.  Mucous membranes are dry and there is tenderness in the right lower quadrant of the abdomen.  Laboratory evaluation shows mild leukocytosis, normal serum electrolytes, borderline low serum glucose levels, and moderate ketones in the urine.  Based on the evaluation, it is suspected that this patient is utilizing ketone bodies as a significant reserve of energy.  Which of the following tissues cannot use this energy source?

A)Brain
B)Erythrocytes
C)Heart muscle
D)Renal cortex
E)Skeletal muscle

Question 62

A 66-year-old man comes to the office due to progressive vision impairment over the last year that has begun to affect his ability to drive.  He has difficulty reading road signs at night and reports excessive glare from the headlights of oncoming cars.  The patient has a long history of hypertension and type 2 diabetes mellitus.  Funduscopy reveals a diminished red reflex bilaterally with obscuration of retinal detail.  It is determined that the patient's condition is in part due to intracellular accumulation of sorbitol.  In healthy cells, this sugar alcohol is normally metabolized into which of the following substances to facilitate excretion?

A)Fructose
B)Galactitol
C)Galactose
D)Glucose
E)Xylulose

Question 63

A 78-year-old man comes to the office due to a one-month history of progressive dyspnea, generalized weakness, fatigue, and palpitations.  He also reports tingling and numbness in both lower limbs.  His daughter, who is visiting from another state, adds that since his wife's death a year ago, the patient has not been taking care of himself.  Blood pressure is 105/50 mm Hg and pulse is 104/min.  Cardiovascular examination shows a displaced apical impulse at the sixth intercostal space, a third heart sound, and high-volume, collapsing carotid pulses.  Bilateral basal crackles, 2+ bilateral pedal edema, and mild hepatomegaly are also present.  Neurologic examination shows decreased light touch and vibration sense in the feet, with decreased knee and ankle reflexes bilaterally.  Laboratory evaluation shows normal blood counts.  Deficiency of which of the following nutrients is most likely responsible for this patient's symptoms?

A)Ascorbic acid
B)Cobalamin
C)Niacin
D)Pyridoxine
E)Retinol
F)Riboflavin
G)Thiamine

Question 64

A 42-year-old woman comes to the neurologist for enrollment in a research study.  She has a 15-year history of resting tremor, bradykinesia, and cogwheel rigidity consistent with Parkinson's disease.  One of her siblings recently started having similar symptoms.  Genetic analysis is performed on the patient and her affected sibling.  The results show a loss-of-function mutation in a gene that leads to an accumulation of misfolded proteins.  Which of the following biochemical processes is most likely defective in this patient?

A)Acetylation
B)Gamma-carboxylation
C)Glucuronidation
D)Phosphorylation
E)Ubiquitination

Question 65

A 2-year-old boy is brought to the emergency department with fever, vomiting, and sleepiness.  He had several episodes of emesis this morning, and his mother was unable to wake him from his afternoon nap.  The boy has had mild rhinorrhea and fever for the past 3 days.  Since the newborn period, the parents say that the patient has had multiple illnesses characterized by vomiting and sleepiness.  Prior laboratory testing revealed increased blood ammonia levels during these episodes and markedly increased orotic acid excretion in the urine.  Physical examination shows a tachypneic boy who is unresponsive to all stimuli.  Which of the following enzymes is most likely to be deficient in this patient?

A)Carbamoyl phosphate synthetase I
B)Hypoxanthine-guanine phosphoribosyltransferase
C)N-acetylglutamate synthetase
D)Ornithine transcarbamylase
E)Uridine monophosphate synthetase

Question 66

A 78-year-old woman comes to the office due to tenderness and easy bleeding of the gums when she brushes her teeth.  The patient has brushed her teeth twice a day for as long as she can remember and has not experienced these symptoms before.  Physical examination shows swollen gingiva that bleed on probing.  Her skin findings are shown in the image below. Further questioning reveals that the patient lives alone and that her diet consists primarily of tea and toast.  Her symptoms are most likely caused by hypoactivity of an enzyme found in which of the following compartments?

A)Extracellular space
B)Golgi apparatus
C)Lysosomes
D)Mitochondria
E)Nucleus
F)Rough endoplasmic reticulum

Question 67

A 4-day-old boy born to a 23-year-old woman is brought to the office for evaluation of poor feeding and vomiting.  The pregnancy was uneventful and the mother had a normal delivery.  Family history is noncontributory.  The patient's temperature is 37.2 C (99 F), blood pressure is 60/30 mm Hg, pulse is 110/min, and respirations are 56/min.  Physical examination reveals a lethargic newborn with exaggerated deep tendon reflexes and clonus.  Further investigation reveals that the patient has an inherited condition that results in impaired transport of ornithine from the cytosol to the mitochondria.  Nutritional restriction of which of the following substances can improve this patient's condition?

A)Branched-chain amino acids
B)Fructose
C)Galactose
D)Medium-chain triglycerides
E)Phenylalanine
F)Proteins
G)Pyridoxine

Question 68

A 56-year-old man is evaluated for progressive visual impairment.  The patient works as part of the grounds crew at an airport, and says he has trouble identifying aircraft at a distance and with filling out paperwork at the end of his shift.  His medical history includes poorly controlled diabetes mellitus, hypertension, and gout.  A year ago, the patient underwent an uncomplicated repair of a right inguinal hernia.  Physical examination shows bilateral clouding of the lens.  The remainder of the examination is unremarkable.  Which of the following metabolic conversions is most likely contributing to this patient's current condition?

A)Galactitol to tagatose
B)Galactose to galactitol
C)Glucose to sorbitol
D)Glucose-6-phosphate to 6-phosphogluconolactone
E)Pyruvate to lactate

Question 69

A 3-year-old boy is brought to the office due to abnormal motor development.  He was born at 40 weeks gestation and had an unremarkable perinatal course.  The boy developed normally during the first year of life.  However, for the past 2 years, he has had progressive bilateral leg stiffness and abnormal involuntary movements.  His cognitive and motor development is also delayed.  There is no significant family history of neurological or muscular disorders.  The patient's height, weight, and head circumference are below the 3rd percentile.  Examination shows bilateral spastic paresis of his lower extremities and frequent choreoathetoid movements.  Comprehensive laboratory testing reveals significantly elevated arginine levels in plasma and cerebrospinal fluid.  The deficient enzyme in this patient is normally involved in the production of which of the following?

A)γ-aminobutyric acid
B)Glutamine
C)Homocysteine
D)Orotic acid
E)Serotonin
F)Urea

Question 70

A 14-year-old boy is brought to the emergency department due to excessive urination and thirst.  He has lost 4.5 kg (10 lb) in the last 3 weeks.  The patient has no past medical problems.  His father has type 1 diabetes mellitus.  Physical examination shows dry mucous membranes.  Laboratory studies reveal blood glucose of 455 mg/dL, normal anion gap, and hemoglobin A1c of 11.3%.  The patient is diagnosed with type 1 diabetes, and treatment with insulin is initiated.  In addition to lowering blood glucose, insulin increases glycogen synthesis in hepatocytes.  Activation of which of the following molecules most likely promotes this metabolic effect?

A)Janus kinase (JAK)
B)Lipoxygenase
C)Phospholipase C
D)Protein kinase A
E)Protein phosphatase

Question 71

A 34-year-old woman is brought to the emergency department in the early morning with confusion, tremor, and sweating.  Her husband reports that she did not wake to her alarm clock and was difficult to arouse.  Over the past week, the patient has had similar episodes in the morning before eating and after exercise.  Past medical history is unremarkable.  Blood pressure is 135/95 mm Hg, pulse is 110/min, and respirations are 24/min.  The patient is arousable to voice but does not follow commands.  Cranial nerve examination, muscle tone, and deep tendon reflexes are normal.  A bedside fingerstick glucose level is 35 mg/dL.  The patient is given an intravenous infusion of glucose, which rapidly improves her mental status.  Further evaluation reveals that her episodes of hypoglycemia are due to increased levels of an endogenous hormone.  This hormonal imbalance is most likely causing the patient's symptoms by stimulating which of the following conversions?

A)A
B)B
C)C
D)D
E)E
F)F

Question 72

A 23-year-old man is brought to the emergency department by paramedics following a motor vehicle accident.  He was an unrestrained passenger in the front seat.  Several days after hospitalization, his fluid volume and plasma osmolarity are measured and illustrated in the image below (solid line, normal; dotted line, patient). Which of the following conditions is most likely to cause the findings shown in the image?

A)Acute gastrointestinal hemorrhage
B)Adrenal insufficiency
C)Diabetes insipidus
D)Hypertonic saline infusion
E)Primary polydipsia

Question 73

A 24-year-old postpartum woman comes to the office for follow-up of gestational diabetes.  The patient was diagnosed with gestational diabetes mellitus during routine screening at 28 weeks gestation; she was treated with dietary modification and exercise and required insulin briefly.  Since delivery 12 weeks ago, she has continued to follow dietary recommendations, and her blood glucose has been fairly well controlled without insulin.  The patient has fasting blood glucose levels of 100-120 mg/dL.  Medical history is otherwise unremarkable.  Family history is significant for diabetes mellitus in her mother and gestational diabetes in her sister.  Vital signs are within normal limits.  BMI is 22 kg/m².  Physical examination shows no abnormalities.  Her gestational diabetes and fasting hyperglycemia are suspected to be genetically predisposed.  This patient's condition is most likely caused by reduced activity of which of the following enzymes?

A)Aldolase A
B)Enolase
C)Glucokinase
D)Lactate dehydrogenase
E)Phosphofructokinase
F)Pyruvate carboxylase
G)Pyruvate kinase

Question 74

A 5-year-old boy with developmental delay is brought to the office due to difficulty "seeing the board" at school.  Examination shows a boy with a tall, thin habitus with elongated limbs.  Funduscopy shows bilateral lens subluxation.  Four years later, the patient dies suddenly of a massive cerebrovascular accident.  Autopsy shows middle cerebral artery thrombosis and old renal infarcts.  His parents wish to know if anything could have been done to have prevented his death.  Which of the following would have been the most appropriate supplementation for this patient?

A)Ascorbic acid
B)Carnitine
C)Pyridoxine
D)Thiamine
E)Tyrosine
F)Vitamin K

Question 75

Researchers are investigating the relationship between glucose transport proteins and insulin concentration in different types of tissues.  Experiments in which cells are taken from various tissue samples and exposed to increasing concentrations of insulin are performed.  The number of surface glucose transporters are then measured.  The results from 2 cell samples are plotted on the graphs below.     Which of the following cell types are most likely represented in cell samples A and B, respectively?

Question 76

A 36-year-old man comes to the office due to skin lesions on his palms.  The patient has yellowish skin nodules over the palmar creases that have been increasing in size and number over the past several years.  He also has small clusters of yellow papules on his elbows, knees, and buttocks.  His father died of a myocardial infarction at age 56.  Biopsy of his lesions shows accumulation of lipid-laden macrophages.  Immunoblot analysis suggests a lack of ApoE3 and ApoE4 in his circulating lipoproteins.  Which of the following is most likely impaired in this patient?

A)ApoC-2 production
B)Cholesterol esterification in the blood
C)Chylomicron remnant uptake by liver cells
D)LDL particle uptake by hepatocytes
E)Lipoprotein lipase activity

Question 77

A 45-year-old man is referred to an endocrinologist for newly diagnosed diabetes mellitus.  A week ago, his primary care physician noted an elevated fasting serum glucose level.  The endocrinologist discusses the different treatment options available, including oral and injectable medications.  He recommends treatment with a medication that alters glucose metabolism within the liver by increasing the concentration of fructose 2,6-bisphosphate within hepatocytes.  Which of the following conversions will be inhibited by high intracellular concentrations of this metabolite?

A)Acetyl CoA → fatty acids
B)Alanine → glucose
C)Fructose-6-phosphate → fructose-1,6-bisphosphate
D)Glucose → glycogen
E)NAD⁺ → NADH

Question 78

A 55-year-old man comes to the office for follow-up of hypertension and coronary heart disease.  He has been on several medications in the past with suboptimal blood pressure control.  The physician considers adding verapamil to the patient's current regimen, as its vasodilatory properties make it useful for controlling systemic hypertension.  Verapamil also affects cardiac contractility but has a minimal effect on skeletal muscle.  Which of the following properties of skeletal muscle is responsible for its resistance to the medication?

A)Calmodulin-independent excitation-contraction coupling
B)Decreased troponin affinity to intracellular calcium
C)Elaborate T-tubular system
D)Lack of internal automaticity
E)Little dependence on extracellular calcium influx

Question 79

A 2-year-old boy is brought to the office by his parents.  He is currently toilet-training during the day and at nighttime.  After he urinated in the toilet last night, his parents forgot to flush the toilet and noticed that the boy's urine turned black overnight.  The child has no significant past medical history and takes no medications.  He can say 2-word sentences, follow 2-step directions, and jump with 2 feet off the ground.  Examination shows a well-nourished child with no swelling or tenderness of any joints.  Urinalysis results are as follows: Which of the following conversion pathways is most likely deficient in this patient?

A)Leucine to acetoacetate
B)Phenylalanine to tyrosine
C)Serine to cysteine
D)Tyrosine to fumarate
E)Valine to glutamic acid

Question 80

A 34-year-old man is admitted to the hospital after sustaining a head injury and fractures of both femurs in a motor vehicle collision.  CT scan of the head reveals a left-sided extradural hematoma.  He has no history of chronic illness and takes no medications.  The patient receives intravenous fluid boluses and blood transfusions and is taken to the operating room for fracture repair and removal of the hematoma.  On the first postoperative day, laboratory results show high plasma glucose and lactate levels.  Which of the following is the primary contributor to this patient's elevated blood glucose levels?

A)Administration of intravenous fluid boluses
B)Decreased hepatic glycerol supply
C)Increased anaerobic glycolysis
D)Increased hepatic glucose production
E)Increased renal gluconeogenesis