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 61-year-old man is brought to the emergency department after being found unresponsive on a sidewalk.  Paramedics noted that the patient’s breath smelled of alcohol and that he had vomitus in his mouth.  The patient also has agonal respirations, and cardiac monitoring shows pulseless electrical activity.  Resuscitation efforts are unsuccessful, and he is pronounced dead on arrival.  Autopsy shows that the cause of death is airway occlusion by aspirated vomitus.  In addition, foci of hemorrhage and necrosis are seen in the mammillary bodies and gray matter surrounding the third and fourth ventricles.  This patient’s brain findings are most likely associated with a decrease in which of the following?

A 42-year-old man comes to the office due to numbness and tingling in both legs and difficulty walking for the past several months.  He has also noticed that he tires more easily with physical activity.  Temperature is 36.8 C (98.2 F), blood pressure is 122/86 mm Hg, pulse is 76 /min, and respirations are 14/min.  Physical examination shows conjunctival pallor and loss of vibration and position sensation in the bilateral lower extremities with associated gait ataxia.  The remainder of the examination is within normal limits.  Which of the following findings is most likely to be present on further questioning of the patient?

In an animal experiment, murine proerythroblasts are cultured in 2 different growth media; the first medium is folate deficient, whereas the second (control) is supplemented with additional folic acid.  Both media contain high concentrations of erythropoietin.  Over 48 hours, cells in the control media proliferate and differentiate into reticulocytes, whereas in the folate-deficient media, cell proliferation is minimal, with the majority of cells undergoing apoptosis.  In another experiment, a substance is added to the folate-deficient media; this substance prevents apoptosis and permits proliferation of some of the proerythroblasts.  Which of the following is the most likely substance added to the growth medium?

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 6-month-old boy is brought to the office by his mother out of concern that he is not developing normally.  He has been feeding regularly and has had no medical problems other than a mild respiratory infection a month earlier.  However, the mother says, “he doesn’t seem to be as interactive as my other children were at his age.”  Physical examination reveals delayed developmental milestones and hypotonia.  Two years later, the child is found to have involuntary movements and demonstrates a tendency to aggressively bite his own lips and fingers.  Laboratory analysis shows an elevated blood uric acid level.  Activity of which of the following enzymes is most likely increased as a result of this patient’s condition?

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?

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Incidentally, one of the male patients followed in the study is hospitalized with right knee pain and swelling.  A sample of his synovial fluid shows negatively birefringent crystals under polarized light microscopy.  To achieve rapid improvement in this patient’s symptoms, therapy should be directed toward inhibiting which of the following types of cells?

As part of a long-term cohort study, members of a large extended family undergo periodic analysis of multiple serum markers.  Many male participants are found to have abnormal laboratory results despite no obvious signs of disease.  Further analysis shows that these men have an X-linked mutation affecting the phosphoribosyl pyrophosphate (PRPP) synthetase gene, resulting in greatly increased substrate conversion.

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Which of the following organs is most likely to develop pathology secondary to this mutation?

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 13-year-old boy is brought to the emergency department for evaluation of a rash and difficulty walking.  A couple of weeks ago, the patient’s mother noticed that he was walking with a slight limp.  There were also a few red spots on his legs at that time.  Over the past couple of days, the rash has progressed, and he now seems to have pain in both legs.  The patient has autism and is nonverbal.  He is a picky eater and takes no medications.  Examination shows tenderness to palpation of his bilateral lower extremities.  The patient requires assistance to stand.  Reflexes are intact.  Skin examination is shown in the exhibit.  Oropharyngeal examination shows poor dentition with swollen, tender gums.  Imaging studies reveal subperiosteal hematomas affecting the bilateral tibias.  A deficiency of which of the following is the most likely cause of this patient’s clinical findings?

A 52-year-old woman comes to the office with a 2-month history of skin rash that worsens with sun exposure.  Her family says that lately she has become irritable and hostile and has had episodes of disorientation.  The patient does not use tobacco or recreational drugs but has been drinking a half bottle of gin daily.  Further questioning reveals poor nutritional intake and intermittent diarrhea.  The patient restricts her diet for weight control.  BMI is 17 kg/m².  On examination, she has a well-demarcated, hyperpigmented, scaly rash on the hands, forearms, and upper chest.  It is determined that the patient is deficient in a vitamin that is used to synthesize the NAD⁺ coenzyme.  Which of the following substances can also be used as a precursor during production of this coenzyme?

A 46-year-old man comes to the emergency department due to recurrent nosebleeds.  When interviewed for additional history, he becomes belligerent and uncooperative.  A review of medical records shows that the patient has a history of alcohol use disorder; he has been placed in homeless shelters on multiple occasions but has not remained there for any prolonged periods.  Physical examination shows swollen gums, scattered ecchymoses, and follicular hyperkeratosis.  He also has a chronic ulcer on the left lower extremity that does not appear to be infected.  Which of the following mechanisms most likely accounts for this patient’s examination findings?

A 31-year-old previously healthy man comes to the office due to myalgias, anorexia, and skin rash.  He does not use tobacco, alcohol, or illicit drugs.  The patient works as a personal trainer and is a bodybuilding enthusiast.  He denies using anabolic steroids but has been consuming large amounts of raw egg whites for the past several months.  Physical examination shows macular dermatitis of the extremities.  A water-soluble vitamin deficiency is suspected as the cause of his condition.  Which of the following biochemical conversions most likely uses the deficient vitamin as a cofactor?

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 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?