Studies in our laboratory have established that N-phosphoryl creatinine (PCrn) is an unusually high energy phosphate compound and that under physiological conditions of temperature, pH and ionic strength PCrn readily forms two biologically important compounds, namely phosphocreatine (PCr) and creatinine (Crn). The presence of PCrn in rabbit white skeletal muscle has been demonstrated. Our goal is to continue these studies on the unusual reactivity of PCrn in in vitro systems in order to understand the possible biological role of this novel high energy compound in cellular energy metabolism.
Our specific aims are: (1) to establish the subcellular distribution of PCrn in muscle utilizing synthetic 32p labelled PCrn, (2) to investigate the mechanism of PCrn(reversible)Pcr interconversion, and (3) to determine the phosphorylating potential of PCrn especially with a view to see if PCrn is able to nonenzymatically phosphorylate amino acids and amino acid residues in peptide and proteins. It is known that the creatine kinase-mediated PCr-ATP energy buffer system operates in several cell processes. This study will help determine the extent and mechanism(s) by which PCr is converted to PCrn which, inturn, will be essential to understand an aspect of cellular energy metabolism not known hitherto. Since several organs and tissues depend on PCr-ATP energy buffer system (e.g., heart, brain and muscles), the determination of factors leading to this new pathway of utilization of PCr will be significant in understanding the response of these cells and tissues to hypoxia and other conditions of energy duress.
| Lee, H J; Fillers, W S; Iyengar, M R (1988) Phosphocreatine, an intracellular high-energy compound, is found in the extracellular fluid of the seminal vesicles in mice and rats. Proc Natl Acad Sci U S A 85:7265-9 |
