A 47-year-old male patient presents with painful ahritis in the right big toe and uric acid renal stones. He has been taking allopurinol for his condition. What biochemical defect would likely be found in this patient?
This patient has gout, characterized by painful joints due to the precipitation of uric acid crystals caused by excessive production of uric acid (a minority of cases are associated with underexcretion of uric acid). Kidney disease is also seen due to accumulation of uric acid in the tubules. The disease mostly affects males, and is frequently treated with allopurinol, an inhibitor of xanthine oxidase. Xanthine oxidase catalyzes the sequential oxidation of hypoxanthine to xanthine to uric acid. A defect in urea synthesis would result in the accumulation of ammonia. Phenylketonuria is a disease in which tyrosine cannot be produced from phenylalanine. It is characterized by a musty body odor and mental retardation. Defective topoisomerases would affect DNA unwinding, and therefore replication. Ref: Rodwell V.W. (2011). Chapter 33. Metabolism of Purine & Pyrimidine Nucleotides. In D.A. Bender, K.M. Botham, P.A. Weil, P.J. Kennelly, R.K. Murray, V.W. Rodwell (Eds), Harper's Illustrated Biochemistry, 29e.
A defect in urea synthesis
An abnormality of the purine degradation pathway
An inability to synthesize non-essential amino acids
Defective topoisomerases