Question11

= by:= =Text of the Question:= toc Draw a cartoon that shows how you would use a single radiolabeled compound to distinguish between dietary and hereditary causes of gout. Draw the flux for each compound, and indicate the likely quantitative differences in what you would eventually measure. Citing references for this problem would be helpful, but not critical. You can decide what radiolabeled compound you would use.

=Definition of the Terms:= radiolabeled:

Gout:

Flux:

=Distinguishing between dietary and hereditary causes (including radiolabeled compound):=



Note: This experiment would have to be done on subjects while they were on a restricted, monitored diet.

People with HGPRT deficiencies cannot recycle hypoxanthine to IMP with as great of efficiency as those with normal HGPRT levels. The HGPRT deficiency encourages increased purine synthesis; therefore, more purines are made into uric acid. In order for someone to be designated with increased purine synthesis, they typically have purine excretion levels greater than 600mg/day, while normal subjects have excretion levels of 400mg/day. Considering these numbers, if the patients are injected with radioactive adenine, which is eventually broken down into uric acid, then the HGPRT deficient patients will likely produce 3 radioactive uric acids to every 2 radioactive uric acids produced by HGPRT normal patients. This could be measured in the urine.

=Quantitative differences measured:=

=Flux of compounds:=



=Pathways=

Voet, 3rd ed, Wiley, 1999. Fig 28-4, p. 1074

Voet, 3rd ed, Wiley, 1999. Fig 28-23, p. 1093

=Relevant Literature:=

11.1. [|Puig, J. G., M. L. JimÈnez, et al. (1989). "Adenine nucleotide turnover in hypoxanthine-guanine phosphoribosyl-transferase deficiency: Evidence for an increased contribution purine biosynthesis de novo." Metabolism 38(5): 410-418.] 11.2. [|Kelley, W. N., Rosenbloom, F. M., Henderson, F., and Seegmiller, J. E., 1967, A Specific Enzyme Defect in Gout Associated with the Overproduction of Uric Acid, Proc Natl Acad Sci USA, v. 57 p. 1735-1739.] 11.3. Voet. Biochemistry, 3rd ed, 1999. pp. 1074, 1093.