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 15-year-old boy is found to have unexplained erythrocytosis on routine laboratory analysis.  Evaluation of his immediate family shows that his father and sister also have elevated red cell levels.  Genetic sequencing of the β-globin gene is performed in the affected family members.  The results show a single base substitution at amino acid position 82 that replaces the normal lysine residue with methionine.  Further analysis shows that this amino acid replacement impairs the ionic interaction between the β-subunit and 2,3-bisphosphoglycerate.  As a result of this mutation, the patient’s hemoglobin will be most similar to which of the following hemoglobin types?

A 34-year-old industry worker experiences rapid-onset shortness of breath, dizziness, palpitations, and flushed skin after accidental exposure to chemical fumes.  Examination by an occupational physician shows that the patient is tachypneic and has reddish skin without cyanosis.  The patient is immediately treated with intravenous hydroxocobalamin.  This medication is most likely to improve this patient’s condition via which of the following mechanisms?

A 28-year-old man comes to the emergency department due to anxiety, weakness, dyspnea, and headaches.  He is a graduate student in chemistry and was accidentally exposed to nitrites in his research laboratory.  Physical examination is notable for cyanosis that is not improved by administration of supplemental oxygen via facemask.  Analysis of a sample of arterial blood drawn from this patient prior to any oxygen supplementation is most likely to reveal normal values for which of the following?

A 10-year-old boy comes to the office for a first visit.  His family recently came to the United States as political refugees.  The patient’s mother says that he has required several blood product transfusions due to anemia, but she does not have prior records available with her.  On examination, the patient’s temperature is 37.1 C (98.8 F).  BMI is 21 kg/m².  Examination is notable for conjunctival pallor and moderate splenomegaly.  Laboratory results are as follows:

Enzyme assays performed on circulating blood cells demonstrate low pyruvate kinase activity.  Which of the following is the most likely cause of this patient’s splenomegaly?

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 researcher is studying the role of glucose metabolites in normal cellular function.  A specific human cell type is incubated in glucose-rich media.  Intracellular levels of glucose metabolizing enzymes, intermediate products, and generated ATP are measured.  In these cells, glycolysis of a single glucose molecule always yields pyruvate but sometimes generates no net ATP.  Which of the following cells is most likely being studied in this experiment?

A 24-year-old man is evaluated for episodic anemia, jaundice, and dark urine.  These episodes typically occur after the use of certain drugs or following infection.  Additional history reveals that he has a brother who experiences similar episodes.  Peripheral blood smear reveals red blood cells with the findings shown below.

Deficiency of which of the following enzymes would most likely result in a condition similar to this patient’s presentation?

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 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 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?

Biochemistry researchers are investigating the speed at which various carbohydrates are metabolized within the liver.  They hypothesize that different monosaccharides delivered to the liver have different rates of intracellular metabolism.  Which of the following substances is most likely to have the fastest rate of metabolism in the glycolytic pathway?

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?

An 8-year-old boy of Ashkenazi Jewish ancestry is brought to the office after developing reduced sensitivity to pain, impaired tear formation, and orthostatic hypotension.  Familial dysautonomia is suspected due to the patient’s symptoms and heritage.  This disorder is caused by loss of function of the IKAP protein, which is essential for development and survival of sensory and autonomic neurons.  IKAP gene sequencing reveals a single nucleotide substitution that causes a guanine residue to be replaced by adenine at the highlighted position in the normal gene sequence shown below.  Exon sequences are represented by capital letters and introns by lowercase letters.

Which of the following is the most likely effect of this mutation?

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 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 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 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 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 6-month-old girl is brought to the office by her mother for a check-up appointment.  The mother states, “My baby doesn’t seem to be growing much despite feeding as often as my previous children.  I’m worried that something is wrong with her.”  Height and weight are below the 10th percentile.  Physical examination shows hepatomegaly and hypotonia.  Laboratory results show hypoglycemia and ketoacidosis.  Liver biopsy shows hepatic fibrosis without fat accumulation.  Further analysis reveals excessive amounts of abnormally structured polysaccharides within the cytosol of the hepatocytes.  Which of the following enzymes is most likely deficient in this patient?

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 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 44-year-old man is brought to the emergency department after police officers found him agitated and confused.  During transport to the hospital, he is started on intravenous fluids with dextrose.  On arrival, the patient is disoriented but cooperative.  Physical examination shows bruises on the forehead, forearms, and shins.  Extraocular findings include bilateral horizontal nystagmus and impaired lateral eye movements; however, the ambulance personnel state that the patient’s extraocular movements were normal when they arrived on the scene.  The patient also has an unsteady gait with widely spaced legs and short steps.  Review of the medical record shows that he has been admitted to the hospital with alcohol intoxication several times before.  This patient’s neurologic findings are most likely related to deficiency of a cofactor required for which of the following reactions?

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?

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 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 2-year-old boy who attends daycare is brought to the emergency department due to diarrhea, fatigue, and abdominal cramps.  The parents also state that he has foul-smelling, frothy stools.  The boy is admitted for rehydration and subsequently diagnosed with giardiasis, which is treated with metronidazole.  He improves and is discharged home.  One week after discharge, the boy is seen by the primary health care provider for recurrent symptoms of frothy, loose stools and abdominal bloating and cramping.  Which of the following steps of this pathway is most likely impaired in this patient?