Q1. G6PD catalyzes the regulated step in the pentose phosphate pathway. Which of the following statements concerning G6PD and the pentose phosphate pathway is correct?
A. Deficiency of G6PD occurs only in RBC.
B. Deficiency of G6PD results in an inability to keep glutathione in its functional, reduced form.
C. The pentose phosphate pathway includes one reversible reductive reaction followed by a series of phosphorylated sugar interconversions.
D. The reduced nicotinamide adenine dinucleotide phosphate (NADPH) product of the pentose phosphate pathway is utilized in processes such as fatty acid oxidation.
Q2. The results of JF's CBC were consistent with a hemolytic anemia. Blood chemistry tests revealed an elevation in the bilirubin level. Which of the following statements concerning bilirubin is correct?
A. Hyperbilirubinemia can cause deposition of bilirubin in the skin and sclerae resulting in jaundice.
B. The solubility of bilirubin is increased by conjugating it with two molecules of ascorbic acid in the liver.
C. The conjugated form of bilirubin increases in the blood with a hemolytic anemia.
D. Phototherapy can increase the solubility of the excess bilirubin generated in the porphyrias.
Q3. Why is urinary urobilinogen increased relative to normal in hemolytic jaundice and absent in obstructive jaundice?
Case 7: Joint Pain
Patient Presentation: IR is a 22-year-old male who presents for follow-up 10 days after having been treated in the Emergency Department (ED) for severe inflammation at the base of his thumb.
Focused History: This was IR’s first occurrence of severe joint pain. In the ED, he was given an anti-inflammatory medication. Fluid aspirated from the carpometacarpal joint of the thumb was negative for organisms but positive for needle-shaped monosodium urate (MSU) crystals (see image at right). The inflammatory symptoms have since resolved. IR reports he is in good health otherwise, with no significant past medical history. His body mass index (BMI) is 31. No tophi (deposits of MSU crystals under the skin) were detected in the physical examination.
Pertinent Findings: Results on a 24-hour urine specimen and blood tests requested in advance of this visit reveal that IR is not an undersecretor of uric acid. His blood urate was 8.5 mg/dl (reference = 2.5–8.0). The unusually young age of presentation is suggestive of an enzymopathy of purine metabolism, and additional blood tests are ordered.
Diagnosis: IR has gout (MSU crystal deposition disease), a type of inflammatory arthritis.
Treatment: IR was given prescriptions for allopurinol and colchicine. The treatment goals are to reduce his blood urate levels to <6.0 mg/dl and prevent additional attacks. He was advised to lose weight because being overweight or obese is a risk factor for gout. His BMI of 31 puts him in the obese category. He was also given written information on the association between diet and gout.
Prognosis: Gout increases the risk of developing renal stones. It is also associated with hypertension, diabetes, and heart disease.
Case-Related Questions: Choose the ONE best answer.
Q1. Allopurinol is converted in the body to oxypurinol, which functions as a noncompetitive inhibitor of an enzyme in purine metabolism. Which of the following statements concerning purine metabolism and its regulation is correct?
A. As a noncompetitive inhibitor, oxypurinol increases the apparent Michaelis constant (Km) of the target enzyme.
B. Colchicine inhibits xanthine oxidase, an enzyme of purine degradation.
C. Glutamate provides two of the nitrogen atoms of the purine ring.