De novo purine synthesis in human lymphocytes. Partial co-purification of the enzymes and some properties of the pathway.
A partially purified enzyme extract from lectin-transformed human peripheral blood lymphocytes synthesized purine nucleotides de novo. Although the relatively lower specific activity of the pathway compared with that in the avian liver preparation previously described (Rowe, P. B., McCairns, E., Madsen, G., Sauer, D., and Elliott, H. (1978) J. Biol. Chem. 253, 7711-7721) limited the extent of purification, a number of properties were established: (i) Ammonia could be utilized as readily as glutamine for the synthesis of phosphoribosylamine but only glutamine provided N-3 of the purine ring; (ii) in the presence of either GTP or NAD, AMP or GMP were synthesized; (iii) purine synthesis was inhibited at the level of phosphoribosylamine synthesis by both AMP and GMP, irrespective of whether ammonia or glutamine was the N donor; (iv) while the synthesis of AMP and GMP from IMP was self-regulated, GTP also appeared to be an inhibitor of the synthesis of GMP from IMP; (v) amidophosphoribosyltransferase was isolated from both transformed and nontransformed cells in a low molecular weight form which was converted to a high molecular weight form in the presence of GMP; and (vi) no evidence was obtained for the existence of a classical multienzyme complex for purine synthesis.
D000249:Adenosine Monophosphate / Q000494:pharmacology; D000582:Amidophosphoribosyltransferase / Q000378:metabolism*; D000641:Ammonia / Q000378:metabolism; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D005973:Glutamine / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006157:Guanosine Monophosphate / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000201:enzymology*; D010430:Pentosyltransferases / Q000378:metabolism*; D011685:Purine Nucleotides / Q000096:biosynthesis*; D011687:Purines / Q000096:biosynthesis*
D002250:Carbon Radioisotopes; D011685:Purine Nucleotides; D011687:Purines; D005973:Glutamine; D000249:Adenosine Monophosphate; D000641:Ammonia; D006157:Guanosine Monophosphate; D010430:Pentosyltransferases; D000582:Amidophosphoribosyltransferase; D005998:Glycine