title: The metabolic implications of intracellular circulation.
abstract: Two views currently dominate research into cell function and regulation. Model I assumes that cell behavior is quite similar to that expected for a watery bag of enzymes and ligands. Model II assumes that three-dimensional order and structure constrain and determine metabolite behavior. A major problem in cell metabolism is determining why essentially all metabolite concentrations are remarkably stable (are homeostatic) over large changes in pathway fluxes-for convenience, this is termed the [s] stability paradox. For muscle cells, ATP and O(2) are the most perfectly homeostatic, even though O(2) delivery and metabolic rate correlate in a 1:1 fashion. In total, more than 60 metabolites are known to be remarkably homeostatic in differing metabolic states. Several explanations of [s] stability are usually given by traditional model I studies-none of which apply to all enzymes in a pathway, and all of which require diffusion as the means for changing enzyme-substrate encounter rates. In contrast, recent developments in our understanding of intracellular myosin, kinesin, and dyenin motors running on actin and tubulin tracks or cables supply a mechanistic basis for regulated intracellular circulation systems with cytoplasmic streaming rates varying over an approximately 80-fold range (from 1 to >80 micrometer x sec(-1)). These new studies raise a model II hypothesis of intracellular perfusion or convection as a primary means for bringing enzymes and substrates together under variable metabolic conditions. In this view, change in intracellular perfusion rates cause change in enzyme-substrate encounter rates and thus change in pathway fluxes with no requirement for large simultaneous changes in substrate concentrations. The ease with which this hypothesis explains the [s] stability paradox is one of its most compelling features.
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver, BC Canada V6T 1Z4. PWH@zoology.ubc.ca
authors.forename: P W
authors.initials: PW
authors.lastname: Hochachka
mesh_terms: D000818:Animals; D006706:Homeostasis; D006801:Humans; D009132:Muscles / Q000378:metabolism / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D010710:Phosphates; D010100:Oxygen