Phosphocreatine shuttle / creatine kinase system (human)

The creatine kinase (CK) / phosphocreatine energy-buffer system, which uses the creatine produced by creatine biosynthesis (see MODULE:creatine_biosynthesis) as a spatial and temporal buffer of ATP. This module covers creatine *utilization*, not its synthesis. A single reversible reaction, creatine kinase activity (ATP + creatine <=> ADP + phosphocreatine, GO:0004111), is run in two cellular locations by compartment-specific isozymes to form a shuttle: mitochondrial CK isozymes (CKMT1A/B ubiquitous, CKMT2 sarcomeric) sit in the mitochondrial intermembrane space and use ATP exported from oxidative phosphorylation to phosphorylate creatine, producing phosphocreatine; phosphocreatine, being small and diffusible, moves through the cytosol to sites of high ATP turnover, where cytosolic CK isozymes (CKB brain-type, CKM muscle-type; assembled as CK-BB, CK-MB, and CK-MM dimers) regenerate ATP from phosphocreatine and ADP exactly where it is consumed. The net effect is to shuttle high-energy phosphate from mitochondria to ATPases and to buffer the cytosolic ATP/ADP ratio in tissues with high, fluctuating energy demand (skeletal and cardiac muscle, brain, photoreceptors, spermatozoa). The same enzymes also support a thermogenic "futile creatine cycle" (GO:0140651) in some adipocytes, in which phosphocreatine is hydrolysed back to creatine (releasing heat) rather than donating phosphate to ADP. The catalytic species are oligomers, and the participants here are modelled as protein complexes mirroring Reactome: the mitochondrial limb as alternative homo-octamers and the cytosolic limb as the CK-MM, CK-BB, and CK-MB dimers (the heterodimer being a genuine two-gene-product catalytic unit). This module is distinct from, and downstream of, creatine biosynthesis: it consumes creatine, it does not make it.