FORMATION OF A SUPPLEMENTAL LONG TIME-CONSTANT RESERVOIR OF HIGH ENERGY PHOSPHATE BY BRAIN IN VIVO AND IN VITRO AND ITS REVERSIBLE DEPLETION BY POTASSIUM DEPOLARIZATION

—Brains of mice fed a diet containing 1% cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) accumulated the high energy phosphate compound cyclocreatine-P (1-carboxymethyl-2-imino-3-phosphonoimidazolidine), an analogue of creatine-P (phosphocreatine). During a 50-day feeding period mouse brain cyclocreatine-P increased linearly to 14 μmol/g fresh wt; during this time the total phosphagen level of brain, creatine-P plus cyclocreatine-P, increased from 3 to 15 μmol/g. When the blood-brain barrier was circumvented, a more rapid accumulation of synthetic phosphagen was achieved. Minced brain preparations from 11 to 15-day chick embryos incubated in vitro with 30 mm -cyclocreatine accumulated 10 μmol/g of cyclocreatine-P in 90 min, and this novel high energy phosphate pool could be depleted by incubation with 105 mm -potassium ions or 3 μm -valinomycin. Subsequent regeneration of the depleted pools could also be demonstrated. Brain tissue containing a supplemental reservoir of cyclocreatine-P, which is utilized to regenerate ATP much more slowly than creatine-P, might be better able to withstand anoxia and certain other metabolic stresses, but this has not been established. However, the marked delay of onset of rigor previously shown to occur in ischemic heart and skeletal muscle of cyclocreatine-fed animals is compatible with this suggestion.