With hemolysis, more bilirubin is produced and conjugated. CB is sent to the intestine where it is converted to urobilinogen, some of which is reabsorbed, enters the portal blood, and travels to the kidney. Because the source of urinary urobilinogen is intestinal urobilinogen, urinary urobilinogen will be low in obstructive jaundice because intestinal urobilinogen will be low as a result of the obstruction of the common bile duct (see Figure D).
Case 7: Joint Pain with Gout
Answer = F. Salvage of the purine bases hypoxanthine and guanine to the purine nucleotides inosine monophosphate (IMP) and guanosine monophosphate (GMP) by hypoxanthine-guanine phosphoribosyltransferase (HGPRT) requires 5-phosphoribosyl-1-pyrophosphate (PRPP) as the source of the ribose 1phosphate. Salvage decreases the amount of substrate available for degradation to uric acid. Therefore, a deficiency in salvage results in hyperuricemia (see figure at right). Noncompetitive inhibitors such as oxypurinol have no effect on the Michaelis constant (Km) but decrease the apparent maximal velocity (Vmax).
Colchicine is an anti-inflammatory drug. It has no effect on the enzymes of purine synthesis or degradation. Glutamine (not glutamate) is a nitrogen source for purine ring synthesis. In purine nucleotide synthesis, the purine ring system is constructed on the ribose 5-phosphate provided by PRPP. Allopurinol and its metabolite, oxypurinol, inhibit xanthine oxidase of purine degradation. The amidotransferase is the regulated enzyme of purine synthesis. Its activity is decreased by purine nucleotides and increased by PRPP.
Answer = B. Methotrexate inhibits dihydrofolate reductase, decreasing the availability of N5,N10-methylene tetrahydrofolate needed for synthesis of deoxythymidine monophosphate (dTMP) from deoxyuridine monophosphate (dUMP) by thymidylate synthase (see figure at right). Carbamoyl phosphate synthetase (CPS) II is the regulated enzymic activity of pyrimidine biosynthesis in humans. CPS I is an enzyme of the urea cycle. Orotic aciduria is a rare pathology of pyrimidine synthesis caused by a deficiency in one or both enzymic activities of bifunctional uridine monophosphate synthase. Pyrimidine nucleotide synthesis, like purine synthesis and salvage, requires PRPP.
Increased activity of PRPP synthetase results in increased synthesis of PRPP. This results in an increase in purine nucleotide synthesis beyond need. The excess purine nucleotides get degraded to uric acid, thereby causing hyperuricemia.
Case 8: No Bowel Movement with Cystic Fibrosis