Authentic Biochemistry

 Early stage TCR activated T cells with rampant lactic acid fermentation, fail to  maintain adequate ATP levels , especially when glucose is limiting.This decrease in ATP relative to ADP+AMP results in the activation of AMPK, which inhibits mTOR activity and all subsequent anabolism especially assocaited for  T cell proliferation. Indeed, induced Loss of AMPKα1, will sythetically restore  mTOR signaling and T cell cytokine production, but not proliferation. Although loss of AMPK can restore some functions in glucose-restricted T cells, the cells do not initiate metabolic adaptations necessary to recover ATP levels. In vivo, AMPKα1-deficient T cells have decreased mitochondrial respiration, flux of glutamine into the mitochondria, and ATP:AMP ratios, and therefore fail to proliferate and function effectively. In cardiac and skeletal muscle, AMPK phosphorylates the bifunctional enzyme at a unique SER residue which induces the PFK-2 activation over the phosphatase activity thus stimulating gl