Fumarate, produced from the purine nucleotide cycle, is an intermediate of TCA cycle and enters the mitochondria by converting into malate and utilizing the malate shuttle where it is converted into oxaloacetic acid (OAA). During exercise, OAA either enters into TCA cycle or converts into aspartate in the mitochondria.
As the purine nucleotide cycle produces ammonia (see below in ammonia synthesis), skeletal muscle needs to synthesize glutamate in a way that does not further increase ammonia, and as such the use of glutaminase to produce glutamate from glutamine would not be ideal. Also, plasma glutamine (released from the kidneys) requires active transport into the muscle cell (consuming ATP). Consequently, during exercise when the ATP reservoir is low (ADP>ATP), glutamate is produced from branch-chained amino acids (BCAAs) and α-ketoglutarate, as well as from alanine and α-ketoglutarate. Glutamate is then used to produce aspartate. The aspartate enters the purine nucleotide cycle, where it is used to convert IMP into S-AMP.
:BCAAs + α-Ketoglutarate ⇌ Glutamate + Branch-chain keto acids (BCKAs) (catalyzed by Branched-chain aminotransferases (BCAT))
:Alanine + α-Ketoglutarate ⇌ Pyruvate + Glutamate (catalyzed by alanine transaminase)
:Oxaloacetic acid + Glutamate ⇌ α-Ketoglutarate + Aspartate (catalyzed by aspartate aminotransferase)
When skeletal muscle is at rest (ADP