Diffusion of metabolites

Forster, R., Green, M.H.L. and Priestley, A. (1980). Optimal Levels of S9 fraction in Ames and fluctuation tests apparent importance of diffusion of metabolites from top agar. Carcinogenesis 2 1081-1085. 

Sykova E, Svoboda J, Polak J, Chvatal A (1994) Extracellular volume fraction and diffusion characteristics during progressive ischemia and terminal anoxia in the spinal cord of the rat. J Cereb Blood Flow Metab 14 301-311 Van der Toorn A, Dijkhuizen RM, Tulleken CA, Nicolay K (1996a) Diffusion of metabolites in normal and ischemic rat brain measured by localized 1H MRS. Magn Reson Med 36 914-922... 

Biomembranes (see) are particularly important for compartmentation. Serving both as barriers to free diffusion of metabolites and as a means of communication between separate C, they enable the directed transport of material, resulting in vectorial biochemical reactions. 

Under aerobic conditions, areas under respiring colonies can become anodic and surrounding areas cathodic. A thick biofilm can prevent diffusion of oxygen to cathodic sites and diffusion of aggressive anions, such as chlorides to anodic sites. Outward diffusion of metabolites and corrosion products also is impeded. If areas within the biofilm become anaerobic, the cathodic mechanism can change to reduction of water or microbiologically produced H2S. 

Attempts to unravel the problems posed by cell compartmentation are hampered by the extreme difficulty of determining the exact intracellular location of many enzymes, let alone the distribution of metabolites. Even within a compartment distribution may not be uniform. For example, the existence of multienzyme systems, in which each enzyme is adjacent to the next one in the metabolic pathway, limits the diffusion of metabolites from the site of their production. This inequality of distribution of metabolites within the cell makes it difficult to demonstrate in vitro control processes which may occur in vivo. 

In addition, spectroscopic techniques have been applied for assessment of diffusion properties (e.g., Refs. 52-56). Changes in the diffusion of water molecules and further metabolites reveal pathological alterations of tissue compartments not visualized by other modalities. Information about cellular tissue architecture under normal and pathological conditions can be provided. 

In contrast to mammalian cells, the membrane of bacterial cells is much more complex and, as in the case of Escherichia coli or mycobacteria, it is asymmetric (see Section 1.2.2). The reason for this is that these small cellular life forms depend on diffusion of nutrients and metabolites. All substrates going in and out of the cell must diffuse through their cell walls. This might be one reasons why the surface area to volume ratio is important for bacterial cell shapes. This ratio is determined by the structure of their outer cell wall. To cross such a barrier, mainly by passive diffusion, chemotherapeutics must have other properties in addition to those necessary for suitable pharmacokinetics in the host, as in most cases, the target of the chemotherapeutics is within the cytoplasm. 

Dijkhuizen RM, de Graaf RA, Tulleken KA, Nicolay K (1999) Changes in the diffusion of water and intracellular metabolites after excitotoxic injury and global ischemia in neonatal rat brain. J Cereb Blood Flow Metab 19 341-349... 

In MRI, water protons are of principal interest due to their abundance and dominant contribution to the MR signal. The remainder of this chapter will focus on physiological and pathophysiological aspects of water proton diffusion, although it should be mentioned that proton diffusion of other metabolites has also been investigated with MR spectroscopy (Nicolay et al. 2001). 

Some, but not all, of the benefits conferred by compartmentalization inside lipid bilayer membranes can be achieved by surfaces. Surfaces allow concentration of metabolites, and, if the surface is a mineral that is not in redox equilibrium with its surroundings, a surface can provide a source of energy. Compartmentalization can also be achieved inside porous minerals. For example, the walls of hydrothermal vents are porous and trap organic material6 and may indeed have provided the first compartmentalization that allowed the emergence of metabolism and macromolecules in a protected environment.7 Also, there are tiny pores in rocks, including tubes in chroysotile, and there are microcracks in quartz, both of which could support diffusion and dispersion by currents. 

Substrate channeling is a process by which two or more sequential enzymes in a pathway interact to transfer a metabolite (or intermediate) from one enzyme to another without allowing free diffusion of the metabolite into bulk solvent. (Ovadi, 1991 Srere, 1987 Anderson, 1999). The substrate tunneling is one of fundamental process of regulating enzymatic processes in cells. Glycolysis, biosynthesis of nucleic acids, aminoacids, and fatty acids are found to be among these processes. 

---