Identification of a nerve ending-enriched 29-kDa protein, labeled with [3-32P]1,3-bisphosphoglycerate, as monophosphoglycerate mutase: inhibition by fructose-2,6-bisphosphate via enhancement of dephosphorylation.
Glucose metabolism is of vital importance in normal brain function. Evidence indicates that glycolysis, in addition to production of ATP, plays an important role in maintaining normal synaptic function. In an effort to understand the potential involvement of a glycolytic intermediate(s) in synaptic function, we have prepared [3-32P]1,3-bisphosphoglycerate and [32P]3-phosphoglycerate and sought their interaction with a specific nerve-ending protein. We have found that a 29-kDa protein is the major component labeled with either [3-32P]1,3-bisphosphoglycerate or [32P]3-phosphoglycerate. The protein was identified as monophosphoglycerate mutase (PGAM). This labeling was remarkably high in the brain and synaptosomal cytosol fraction, consistent with the importance of glycolysis in synaptic function. Of interest, fructose-2,6-bisphosphate (Fru-2,6-P2) inhibited PGAM phosphorylation and enzyme activity. Moreover, Fru-2,6-P2 potently stimulated release of [32P]phosphate from the 32P-labeled PGAM (EC50 = 1 microM), suggesting that apparent reduction of PGAM phosphorylation and enzyme activity by Fru-2,6-P2 may be due to stimulation of dephosphorylation of PGAM. The significance of these findings is discussed.
Ikemoto
Atsushi
A
Mental Health Research Institute, The University of Michigan Medical School, Ann Arbor, Michigan 48109-0669, USA.
Ueda
Tetsufumi
T
D000818:Animals; D002417:Cattle; D004163:Diphosphoglyceric Acids / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005635:Fructosediphosphates / Q000378:metabolism / Q000494:pharmacology*; D006019:Glycolysis; D009411:Nerve Endings / Q000201:enzymology*; D009928:Organ Specificity; D010736:Phosphoglycerate Mutase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D013347:Subcellular Fractions / Q000737:chemistry
D004163:Diphosphoglyceric Acids; D005635:Fructosediphosphates; D010761:Phosphorus Radioisotopes; C015891:glycerate 1,3-biphosphate; C027652:fructose 2,6-diphosphate; D010736:Phosphoglycerate Mutase