Facilitated diffusion

Abstract: The diffusive mobility of solutes chemically connected by reversible reactions in cells is analyzed as a problem of facilitated diffusion. By this term we mean that the diffusive flux of any substance, X, which is in one metabolic pathway, is effectively increased when it participates in a second and equilibrium reaction with another substance Y because the total flux of X in the pathway is the sum of the fluxes of X and Y. This notion is generalized and is seen to include the familiar enhanced intracellular diffusion of oxygen by oxymyoglobin. In this framework the function of creatine kinase (CK) is seen to have two aspects: 1) phosphocreatine (PCr) via the CK reaction buffers the cellular ATP and ADP concentrations and 2) transport of high-energy phosphates is predominantly in the chemical form of PCr. This predominance of PCr is a consequence of the maintained ATP, ADP, and total creatine levels and of the apparent equilibrium constant of the reaction. Thus experimental results demonstrating the transport aspects of the CK reaction emphasize only one feature of a more general notion of facilitated diffusion by near-equilibrium metabolic reactions and do not per se establish the existence of any physical or functional compartmentation of ATP, ADP, PCr, or creatine. PCr can be a large source for increasing inorganic phosphate levels during contractile activity, possibly as a metabolic regulator. Neither the transport nor buffer aspects can be quantitatively important in cells with small distances between ATP-utilizing and ATP-generating sites, such as is the case with cardiac myofibrils and mitochondria.

Abstract: Components of Biological Membranes Self- Association of Phospholipids Properties of Bilayers Order and Dynamics in Bilayers Solutes in Bilayers Lipid-Protein Interactions in Membranes Glycoproteins and Glycolipids Ionophores: Models for Channels and Carriers Facilitated Transport Coupled Transport Gated Channels Energy Transduction Transbilayer Response of Signals Bulk Transport by Fusion and Secretion.

Abstract: Passive macromolecular diffusion through nuclear pore complexes (NPCs) is thought to decrease dramatically beyond a 30-60-kD size threshold. Using thousands of independent time-resolved fluorescence microscopy measurements in vivo, we show that the NPC lacks such a firm size threshold; instead, it forms a soft barrier to passive diffusion that intensifies gradually with increasing molecular mass in both the wild-type and mutant strains with various subsets of phenylalanine-glycine (FG) domains and different levels of baseline passive permeability. Brownian dynamics simulations replicate these findings and indicate that the soft barrier results from the highly dynamic FG repeat domains and the diffusing macromolecules mutually constraining and competing for available volume in the interior of the NPC, setting up entropic repulsion forces. We found that FG domains with exceptionally high net charge and low hydropathy near the cytoplasmic end of the central channel contribute more strongly to obstruction of passive diffusion than to facilitated transport, revealing a compartmentalized functional arrangement within the NPC.