Purines, Pyrimidines and Nucleic Acid Metabolism
A one-year-old female patient is lethargic, weak, and anemic. Her height and weight are both low for her age. Her urine contains an elevated level of orotic acid. The administration of which of the following compounds is most likely to alleviate her symptoms?
a. The elevated excretion of orotic acid indicates that the patient has orotic aciduria, a genetic disorder affecting the de novo pyrimidine biosynthetic pathway.
b. Deficiencies in the enzyme activities OMP decarboxylase and/or orotate phosphoribosyltransferase (both of which are domains of the enzyme UMP synthase) leave the patient unable to synthesize pyrimidines.
c. Uridine, a pyrimidine nucleoside, is useful in treating this disorder because it bypasses the missing enzymes and can be salvaged to UMP, which can be converted to all the other pyrimidines.
d. Although thymidine is a pyrimidine nucleoside, it cannot be converted to other pyrimidines. Hypoxanthine, guanine, and adenine are all purine bases that have no value in helping to replace the missing pyrimidines.