Two successive steps in de novo purine biosynthesis are catalyzed by the enzymes 5-aminoimidazole ribonucleotide (AIR) carboxylase and 4-[(N-succinylamino)carbonyl]-5-aminoimidazole ribonucleotide (SAICAR) synthetase. In vertebrates, a bifunctional enzyme, ADE2 ( also designated PurCE/AIRC) catalyzes successive carboxylation and aspartylation steps of AIR to form SAICAR. ADE2 is transcribed from a 558 bp intergenic promoter region, which is bound by NRF-1 and Sp1 at sites within the 215-260 region. The intergenic region is an integrated bidirectional promoter and a novel initiator-like element plays a central role in coordinating expression of the divergently transcribed ADE2 and GPAT genes. The ADE2 mRNA levels increase approximately five to six fold in G1/S phase of the cell cycle over those in G0 phase in synchronized rat 3Y1 fibroblasts . The ADE2 gene encodes enzyme of AIRC at step 6 and SAICR synthetase at step 7 in de novo purine nucleotide synthesis . The ADE2 encoded enzyme has no ATP dependence and no common cofactors or metals are required for catalysis . Activities of ADE2 enzyme are found in lysates of human erythrocytes, thrombocytes and leukocytes and in homogenate of the stomach biopsy sample, but not in blood plasma and bile .
