It has also been suggested that evolutionary changes were developed to set a particular level of focal synaptic ratio of CNS excitation; inhibition based upon metabolic protection of hypoxia and hypoglycemia and dependent upon synthesis of GABA from glutamate (dependent upon input from acetyl CoA and citrate from the Krebs cycle (through GAD)) and degradation of GABA (by GABA transaminase to succinic semialdahyde to succinate and back into the Krebs cycle [305]). The gene discussed is GAD1; the disease is Hypoglycemia.