CASE 1 A 48-year-old male presents to the clinic because of concerns about heart disease.

He reports that his father died from a heart attack at age 46, and his older brother has also had a heart attack at age 46 but survived and is on medications for elevated cholesterol. The patient reports chest pain occasionally with ambulation around his house and is not able to climb stairs without significant chest pain and shortness of breath. The physical exam is normal, and the physician orders an electrocardiogram (ECG), exercise stress test, and blood work. The patients cholesterol result comes back as 350 mg/dL (normal 200). The physician prescribes medication, which he states is directed at the ratelimiting step of cholesterol biosynthesis. What is the rate-limiting step of cholesterol metabolism? What is the class of medication prescribed? CASE 2 Lofata Burne is a 16-year-old girl. Since age 14 months she has experienced recurrent episodes of profound fatigue associated with vomiting and increased perspiration, which required hospitalization. These episodes occurred only if she fasted for more than 8 hours. Because her mother gave her food late at night and woke her early in the morning for breakfast, Lofatas physical and mental development had progressed normally.On the day of admission for this episode, Lofata had missed breakfast, and by noon she was extremely fatigued, nauseated, sweaty, and limp. She was unable to hold any food in her stomach and was rushed to the hospital, where an infusion of glucose was started intravenously. Her symptoms responded dramatically to this therapy. Her initial serum glucose level was low at 38 mg/dL (reference range for fasting serum glucose levels _ 70100). Her blood urea nitrogen (BUN) level was slightly elevated at 26 mg/dL (reference range _ 825) as a result of vomiting, which led to a degree of dehydration. Her blood levels of liver transaminases were slightly elevated, although her liver was not palpably enlarged. Despite elevated levels of free fatty acids (4.3 mM) in the blood, blood ketone bodies were below normal. What happened with Lofata Burne? CASE 3 A 63-year-old female presents to the clinic with recurrent midepigastric pain over the last 3 months. She reports some relief shortly after eating, but then the discomfort returns. She has tried various over-the-counter medications without relief. She also reports feeling tired and has had to increase the amount of ibuprofen needed for relief of her arthritis. She denies nausea,

vomiting, and diarrhea. On exam she is found to have mild midepigastric tenderness and guaiac positive stool. A CBC revealed a microcytic anemia and normal white blood cell count, consistent with iron deficiency. The patient was referred to a gastroenterologist who performed an upper GI endoscopy that identified gastric ulcers. He stated that he suspected that the ibuprofen, a nonsteroidal antiinflammatory drug (NSAID) was the causative agent and suggested switching from ibuprofen to a coxib, such as celecoxib. What is the likely biochemical etiology of the disorder? Why do coxibs generally have a lower incidence of upper GI problems than other NSAIDs? What is the major difference between aspirin and other NSAIDs with regard to platelet function? CASE 4 Diana, a 27-year-old woman with type 1 diabetes mellitus, had been admitted to the hospital in a ketoacidotic coma a year ago. She had been feeling drowsy and had been vomiting for 24 hours before that admission. At the time of admission, she was clinically dehydrated, her blood pressure was low, and her breathing was deep and rapid (Kussmaul breathing). Her pulse was rapid, and her breath had the odor of acetone. Her arterial blood pH was 7.08 (reference range, 7.367.44), and her blood ketone body levels were 15 mM (normal is approximately 0.2 mM for a person on a normal diet). What happened with Diana? CASE 5 Since her admission to the hospital for an acute myocardial infarction, Ann Jeina has been taking the bile salt sequestrant cholestyramine and the HMG-CoA reductase inhibitor pravastatin to lower her blood cholesterol levels. She also takes 160 mg acetylsalicylic acid (ASA; aspirin) each day. At her most recent visit to her cardiologist, she asked whether she should continue to take aspirin because she no longer has any chest pain. She was told that the use of aspirin in her case was not to alleviate pain but to reduce the risk of a second heart attack and that she should continue to take this drug for the remainder of her life unless a complication, such as gastrointestinal bleeding, occurred as a result of its use. What happened with Ann Jeina? CASE 6

Emma Wheezer has done well with regard to her respiratory function since her earlier hospitalization for an acute asthmatic attack. She has been maintained on two puffs of triamcinolone acetonide, a potent inhaled corticosteroid, three times per day, and has not required systemic steroids for months. The glucose intolerance precipitated by high intravenous and oral doses of the synthetic glucocorticoid dexamethasone during her earlier hospitalization resolved after this drug was discontinued. She has come to her doctor now because she is concerned that the low-grade fever and cough she has developed over the last 36 hours may trigger another acute asthma attack. What happened with Emma Wheezer?