title: Metabolic regulation via intracellular pH.
abstract: Despite earlier notions that intracellular pH (pHi) was invariant with time, recent studies have documented pHi changes of from 0.1 to 1.6 U during metabolic and developmental transitions in a variety of cells. Here we review the evidence for pHi-mediated regulation of gamete activation, cellular dormancy, the cell cycle, and stimulus-response coupling. Intracellular Ca2+ level changes also accompany many of these same transitions, and mounting evidence suggests that pHi and Ca2+ changes can be interdependent, both in their mechanisms and their effects. Although the significance of such interactions is still largely unclear, one example--the pronounced pH dependence of Ca2+ binding by calmodulin--suggests their potential importance in metabolic regulation. Similar evidence suggests that pHi changes also influence intracellular adenosine 3',5'-cyclic monophosphate levels, and vice versa. Finally we show that changes in adenylate energy charge can significantly alter pHi. In light of these interactions--and because pHi, unlike most other effectors, does not require specialized receptors--we suggest that pHi functions as a synergistic messenger, providing a metabolic context within and through which the actions of other effectors are integrated.
mesh_terms: D000177:Acrosome / Q000502:physiology; D000818:Animals; D001826:Body Fluids / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002453:Cell Cycle; D002455:Cell Division; D000242:Cyclic AMP / Q000378:metabolism; D004734:Energy Metabolism; D005110:Extracellular Space / Q000032:analysis; D005260:Female; D006706:Homeostasis; D006859:Hydrogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000494:pharmacology; D007424:Intracellular Fluid / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008839:Microelectrodes; D010063:Ovum / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D013081:Sperm Motility; D013094:Spermatozoa / Q000502:physiology
chemical_list: D002147:Calmodulin; D007328:Insulin; D006859:Hydrogen; D012964:Sodium; D000242:Cyclic AMP; D002118:Calcium