KIEs as Mechanistic Probes
KIE measurements are routinely used for the elucidation of reaction mechanisms. The reaction coordinate represents the three-dimensional motion of all nuclei along the lowest-energy path that interconverts reactants and products. The reaction coordinate may represent the displacement of atoms within a chemical bond and or the reorientation of surrounding solvent molecules. Regardless of the nature of the reaction coordinate, isotope substitution does not change the electronic potential energy...
Hexokinase IV Glucokinase
One intriguing aspect of glucokinase, a monomeric enzyme, is that it displays a sigmoidal saturation curve for glucose, with a Hill coefficient of 1.6. This is not due to the presence of a second, allosteric binding site for glucose on the glucokinase monomer, but to the existence of two distinct conformations, with low and high affinity for glucose, that equilibrate slowly as assumed in models designated mnemonical model and slow transition model . If the hypothesis is made that the...
The Arrestin Family of Proteins
Arrestin also termed S-antigen, visual arrestin, or arrestin-1 was initially identified in the visual system as a 48-kDa protein that redistributed from the cytoplasm to the disk membrane following light activation of bovine rod cell outer segments. Arrestin-1 is a 404 amino acid protein and binds to the light-receptor rhodopsin in a light- and phosphorylation-dependent manner resulting in suppression of G protein signaling. Gene targeting has demonstrated a clear physiological role for...
Mitochondrial Outer Membrane and the VDAC Channel
University of Maryland, College Park, Maryland, USA Mitochondria are organelles found in virtually all eukaryotic cells. They are composed of two membranes. The inner membrane is highly convoluted and of quite variable morphology. The outer membrane forms the boundary between the mitochondrial spaces and the cytosol. It contains membrane channels, called VDAC, that allow metabolites to cross this membrane while restricting the passage of proteins. Origin and Structure of the Outer Membrane...
Types of Flavoproteins
To try to display the diversity and utility of flavin function in living systems, we adapt below the classification system for flavoproteins developed by Massey. There is a diverse group of proteins that connects the stable reducing currency of cells NADH NADPH with other redox processes required for cellular function. For example, glutathione reductase is one of a group of related disulfide reductases that contain both FAD and a pair of reactive cysteine residues in the active site. The...
FlFO ATP Synthase
University of Padova, Padova,, Italy F1-F0 ATP synthases also called F1-F0 or F-ATPases are large protein complexes, weighing 550-650 kDa, located in the inner mitochondrial membrane, in the chloroplast thyla-koid membrane and in the bacterial plasma membrane. They are the major ATP suppliers of most cells, synthesizing ATP in the terminal phase of oxidative phosphorylation or photopho-sphorylation. The synthesis of ATP from ADP and inorganic phosphate Pi is driven by protons H1 moving through...
Lipid Bilayer Structure
State University of New York, Stony Brook, New York, USA Natural biological membranes consist of a lipid bilayer in which membrane proteins are embedded. As such, the bilayer is the underlying structural unit of the membrane. Understanding bilayer structure, and properties is critical to an understanding of membrane function. Chemical Structure of Bilayer-Forming Lipids Lipid bilayers are composed primarily of polar lipids. Glycerophospholipids and sphingolipids are usually the predominant...
MembraneAssociated Energy Transduction in Bacteria and Archaea
University of L beck, L beck, Germany Archaea and bacteria represent the two prokaryotic branches of the universal tree of life. Their plasma membranes host protein complexes specialized in primary and secondary energy-transducing mechanisms. Common to bacteria and archaea is the underlying principle of primary energy conservation, the chemiosmotic mechanism generating an electrochemical potential of ions across the membrane on expense of the energy derived from membrane-associated...
Biography Fwr
Vern Schramm received his Ph.D. at the Australian National University, John Curtain School of Medical Research in 1968. In the Department of Biochemistry at the Temple University School of Medicine 1971 , he began to apply isotope effects to the study of enzymatic transition states. At the Albert Einstein College of Medicine in 1987, he began a systematic program of solving enzymatic transition states by kinetic isotope effects. Enzymatic transition-state information is then applied to the...
Fatty Acid Receptors
Lipids provide energy to the organism and contribute to various cellular components, including organelles and plasma membranes. A particular class of lipids are unesterified and are usually known as free fatty acids. Although dietary fatty acids have a major role as nutrients in various types of metabolic functions, some of them also exert more specialized functions as signaling molecules when they act as messengers between cells and within tissues. It became evident in the early 1990s that...
Conservation of ErbB Receptor Signaling during Evolution
ErbB signaling is present not only in mammalians, but also in less-developed organisms such as the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster. The nematode has one EGF-like ligand Lin-3 and one ErbB-like receptor Let23 . These components are required for correct development in the nematode. In the fruitfly the ErbB signaling network consists of four EGF-like ligands Vein, Gurken, Spitz, and Argos and one EGF-like receptor Drosophila EGF receptor - DER . Argos is a...