Alternative titles; symbols
HGNC Approved Gene Symbol: PPAT
Cytogenetic location: 4q12 Genomic coordinates (GRCh38): 4:56,393,362-56,435,615 (from NCBI)
Glutamine phosphoribosylpyrophosphate amidotransferase (EC 2.4.2.14) catalyzes step 1, the presumed rate-limiting reaction, of the de novo purine biosynthetic pathway which proceeds through inosine monophosphate (IMP) (summary by Gavalas et al., 1993). This enzyme is also known as phosphoribosylpyrophosphate amidotransferase, or PRPP amidotransferase (Feldman and Taylor, 1975). The GART gene (138440) encodes the second, third, and fifth steps.
The GPAT gene was isolated in the chicken by Gavalas et al. (1993), who found that GPAT is closely linked to AIRC (172439), the gene encoding the bifunctional AIR carboxylase (EC 4.1.1.21)/SAICAR synthetase (EC 6.3.2.6), the activities of which are required for steps 6 and 7, respectively, in purine nucleotide biosynthesis. Avian GPAT and AIRC were found to be divergently transcribed from a bidirectional promoter with distinct transcriptional start sites 229 bp apart. This was said to be the first example of bidirectional transcription of tightly linked genes that are not structurally related but are involved in the same pathway. The term dioskourion (from Dioskouri, the mythologic inseparable twin sons of Zeus) was suggested to describe this eukaryotic transcriptional unit, which could be the eukaryotic equivalent of a prokaryotic operon.
By somatic cell hybridization, Stanley and Chu (1978) showed that the human gene for this enzyme is on chromosome 4 in the region pter-q21. Jones et al. (1985) showed that PPAT and PGM2 (172000) are both on chromosome 3 of the chimpanzee. Since chimpanzee 3 and human 4 are homologous, further weight is added to the assignment of PPAT to chromosome 4.
Brayton et al. (1994) found that human GPAT and AIRC are closely linked and divergently transcribed from an intergenic region of approximately 625 bp. By fluorescence in situ hybridization, they mapped the GPAT gene to 4q12.
An auxotrophic mutant requiring exogenous purines because of deficiency of this enzyme was isolated from a Chinese hamster cell line by Chu et al. (1972).
Brayton, K. A., Chen, Z., Zhou, G., Nagy, P. L., Gavalas, A., Trent, J. M., Deaven, L. L., Dixon, J. E., Zalkin, H. Two genes for de novo purine nucleotide synthesis on human chromosome 4 are closely linked and divergently transcribed. J. Biol. Chem. 269: 5313-5321, 1994. [PubMed: 8106516]
Chu, E. H. Y., Sun, N. C., Chang, C. C. Induction of auxotrophic mutants by treatment of Chinese hamster cells with 5-bromodeoxyuridine and black light. Proc. Nat. Acad. Sci. 69: 3459-3463, 1972. [PubMed: 4508333] [Full Text: https://doi.org/10.1073/pnas.69.11.3459]
Feldman, R. I., Taylor, M. W. Purine mutants of mammalian cell lines. II. Identification of a phosphoribosylpyrophosphate amidotransferase-deficient mutant of Chinese hamster lung cells. Biochem. Genet. 13: 227-234, 1975. [PubMed: 1147888] [Full Text: https://doi.org/10.1007/BF00486016]
Gavalas, A., Dixon, J. E., Brayton, K. A., Zalkin, H. Coexpression of two closely linked avian genes for purine nucleotide synthesis from a bidirectional promoter. Molec. Cell. Biol. 13: 4784-4792, 1993. Note: Erratum: Molec. Cell. Biol. 13: 7977 only, 1993. [PubMed: 8336716] [Full Text: https://doi.org/10.1128/mcb.13.8.4784-4792.1993]
Jones, C., Morse, H. G., Palmer, D. K. Comparative gene mapping of man and higher primates involving genes assigned to human chromosomes 3, 4, 11, 21. (Abstract) Cytogenet. Cell Genet. 40: 662-663, 1985.
Stanley, W., Chu, E. H. Y. Assignment of the gene for phosphoribosylpyrophosphate amidotransferase to the pter-q21 region of human chromosome 4. Cytogenet. Cell Genet. 22: 228-231, 1978. [PubMed: 752480] [Full Text: https://doi.org/10.1159/000130943]
Zalkin, H., Dixon, J. E. De novo purine nucleotide biosynthesis. Prog. Nucleic Acid Res. Molec. Biol. 42: 259-287, 1992. [PubMed: 1574589] [Full Text: https://doi.org/10.1016/s0079-6603(08)60578-4]