CreatinevsGlycine

Creatine is phosphorylated by mitochondrial creatine kinase (CK-Mt) to form phosphocreatine (PCr), which serves as a rapidly mobilizable high-energy phosphate reserve. When neuronal ATP is consumed during demanding tasks (synaptic vesicle cycling, ion pump activity, action potential propagation), cytosolic brain-type creatine kinase (CK-BB) catalyzes the transfer of the phosphoryl group from PCr to ADP, regenerating ATP within milliseconds — far faster than oxidative phosphorylation or glycolysis can respond. This PCr/CK shuttle also transports high-energy phosphates from mitochondria to distant synaptic sites. Creatine provides direct neuroprotection by stabilizing the mitochondrial permeability transition pore (mPTP), preventing cytochrome c release and downstream apoptotic cascades. It scavenges reactive oxygen species by acting as a direct antioxidant against superoxide and peroxynitrite. Creatine also increases GLUT4 expression in neurons, improving glucose uptake, and upregulates brain-derived neurotrophic factor (BDNF) expression in the hippocampus, supporting synaptic plasticity and memory consolidation.

Glycine acts as an inhibitory neurotransmitter by binding to strychnine-sensitive glycine receptors (GlyR) in the brainstem, spinal cord, and retina, hyperpolarizing neurons via chloride influx. It also serves as a mandatory co-agonist at the glycine-binding site (NR1 subunit) of NMDA glutamate receptors — without glycine binding, NMDA receptors cannot open their ion channel even when glutamate is present. This dual role means glycine both calms neural activity (sleep, anti-anxiety via GlyR) and supports excitatory learning processes (NMDA-dependent LTP and memory consolidation). Glycine lowers core body temperature at night by promoting peripheral vasodilation through nitric oxide, which improves sleep onset. It is a precursor for glutathione synthesis and modulates the glycinergic system in the suprachiasmatic nucleus.