Akt phosphorylates transketolase : : regulatory step of de novo purine synthesis

Akt is a major regulatory protein involved in many cellular processes, particularly cell growth, proliferation, and progression. The objective of this study is to elucidate Akt regulation of de novo purine synthesis. Rates of de novo purine synthesis and phosphoribosyl pyrophosphate availability are subject to regulation by Akt. In this study, I show that rates of de novo purine synthesis and phosphoribosyl pyrophosphate availability decrease with Akt knockout and single essential amino acid starvation (lysine) in mouse embryonic fibroblasts. I also show that Akt phosphorylates and activates transketolase, a key enzyme of the non- oxidative pentose phosphate pathway. This was shown by a series of transketolase activity assays conducted under Akt wild type and Akt knockout, phosphorylated and de- phosphorylated transketolase, and mutated transketolase conditions. Overall, Akt phosphorylation of transketolase is an important regulatory step of de novo purine synthesi