Molecular Transport - Transport of Small Molecules Lecture PDF

Associate professor Zanda Daneberga Molecular transport - Transport of small molecules 1 Small molecules ◼ Water, inorganic ions, and relatively small organic molecules (e.g., sugars, vitamins, fatty acids) account for 75 – 80 % of living matter by weight....

Associate professor Zanda Daneberga Molecular transport - Transport of small molecules 1 Small molecules ◼ Water, inorganic ions, and relatively small organic molecules (e.g., sugars, vitamins, fatty acids) account for 75 – 80 % of living matter by weight. ◼ Ions, water, and many small organic molecules are imported into the cell. ◼ Cells also make and alter many small organic molecules by a series of different chemical reactions. 2 Function of small molecules ◼ Function as precursors for synthesis of macromolecules. ◼ Store and distribute the energy for all cellular processes. ◼ Signalling function. 3 Transport of small molecules ◼ The plasma membrane is selectively permeable to small molecules. ◼ It is defined by molecule`s: size, charge, solubility. ◼ Only small, relatively hydrophobic molecules are able to diffuse across a phospholipid bilayer. 4 5 Passive transport Active transport 6 7 Passive (simple) diffusion ◼ Molecule dissolves in the phospholipid bilayer, diffuses across it, and then dissolves in the aqueous solution at the other side of the membrane. ◼ The direction of transport is determined by the relative concentrations of the molecule inside and outside of the cell. ◼ The transport reactions are spontaneous because they have a positive delta S value (increase in entropy) and thus a negative delta G (decrease in free energy). 8 Facilitated diffusion ◼ Facilitated diffusion is always energetically downhill in the direction determined by electrochemical gradients across the membrane. ◼ Allows polar and charged molecules, such as carbohydrates, amino acids, nucleosides, and ions, to cross the plasma membrane. 9 Facilitated diffusion - continued Facilitated diffusion Carrier proteins Channel proteins Uniporter Non-gated Gated 10 Carrier proteins ◼ Membrane carrier protein that binds to a solute and transports it across the hydrophobic regions of the membrane by undergoing a series of conformational changes. ◼ Called carriers, permeases, or transporters. ◼ All carrier proteins are transmembrane proteins containing multiple membrane-spanning segments that generally are alpha helices. 11 Carrier proteins - continued 12 Carrier proteins - continued ◼ Uniporter – transport a single type of molecule down its concentration gradient (glucose and amino acids). 13 Channel proteins ◼ Channel proteins form a hydrophilic passageway - open pores in the membrane, allowing small molecules of the appropriate size and charge to move through the lipid bilayer. ◼ Transport water or specific types of ions and hydrophilic small molecules down their concentration or electric potential gradients. Non-gated (leak) channels are opened most of time. Gated channels open only in response to specific chemical or electrical signals. 14 Channel proteins - Example ◼ The plasma membranes of many cells contain water channel proteins (aquaporins), through which water molecules are able to cross the membrane much more rapidly than they can diffuse through the phospholipid bilayer. 15  Aquaporins Acuired from: Verkman A. S. (2013). Aquaporins. Current biology : CB, 23(2), R52–R55. https://doi.org/10.1016/j.cub.2012.11.025 16 Channel proteins - Ion channel 17 Ion channel properties ◼ Transport through channels is extremely rapid. ◼ Ion channels are highly selective because narrow pores in the channel restrict passage to ions of the appropriate size and charge. ◼ Non-gated ion channels are permanently open. 18  Ion channel properties - continued ◼ Gated ion channels are not permanently open: ligand-gated channels - open in response to the binding of signalling molecules, involved in generating graded potentials. voltage-gated channels - changes in electric potential across the plasma membrane, involved in generating action potentials. mechanically-gated channels - open and close in response to mechanical vibration or pressure, involved in generating graded potentials. 19 Secondary active transport - Cotransport ◼ Cotransporters use the energy stored in an electrochemical gradient. 20 Primary active transport ◼ In active transport, energy provided by another coupled reaction (such as the hydrolysis of ATP) is used to drive the uphill transport of molecules in the energetically unfavourable direction. 21 22 Primary active transport – ion pumps ◼ The ion pumps maintain gradients of ions across the plasma membrane. It is called active because use energy to ensure transport of ions. ◼ ATP-powered pumps are ATPases that use the energy of ATP hydrolysis to move ions or small molecules across a membrane against a chemical concentration gradient or electric potential or both. 23 Na+/K+ ATPase Adapted from: Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology. 4th edition.New York: W. H. Freeman; 2000. 24 Ion channel defect and human pathology ◼ Cystic fibrosis (CF; MIM #219700): One of the most common single-gene disorders in European origin populations. Caused by allelic variants in a CFTR gene (called the cystic fibrosis transmembrane conductance regulator) - encodes cyclic AMP regulated (ATP binding triggers channel opening, ATP hydrolysis – closure) chloride ion channels transmembrane protein in epithelial cell membranes. Abnormally viscous secretions in the airways of the lungs and in the ducts of the pancreas in individuals with CF cause obstructions that lead to inflammation, tissue damage and destruction of both organ systems. 25 CF 26 CF 27