3. Transport Can Be Active Or Passive. •Passive Transport Is Movement
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Pharmacokinetics, Pharmacodynamics and Drug
pharmaceutics Review Pharmacokinetics, Pharmacodynamics and Drug–Drug Interactions of New Anti-Migraine Drugs—Lasmiditan, Gepants, and Calcitonin-Gene-Related Peptide (CGRP) Receptor Monoclonal Antibodies Danuta Szkutnik-Fiedler Department of Clinical Pharmacy and Biopharmacy, Pozna´nUniversity of Medical Sciences, Sw.´ Marii Magdaleny 14 St., 61-861 Pozna´n,Poland; [email protected] Received: 28 October 2020; Accepted: 30 November 2020; Published: 3 December 2020 Abstract: In the last few years, there have been significant advances in migraine management and prevention. Lasmiditan, ubrogepant, rimegepant and monoclonal antibodies (erenumab, fremanezumab, galcanezumab, and eptinezumab) are new drugs that were launched on the US pharmaceutical market; some of them also in Europe. This publication reviews the available worldwide references on the safety of these anti-migraine drugs with a focus on the possible drug–drug (DDI) or drug–food interactions. As is known, bioavailability of a drug and, hence, its pharmacological efficacy depend on its pharmacokinetics and pharmacodynamics, which may be altered by drug interactions. This paper discusses the interactions of gepants and lasmiditan with, i.a., serotonergic drugs, CYP3A4 inhibitors, and inducers or breast cancer resistant protein (BCRP) and P-glycoprotein (P-gp) inhibitors. In the case of monoclonal antibodies, the issue of pharmacodynamic interactions related to the modulation of the immune system functions was addressed. It also focuses on the effect of monoclonal antibodies on expression of class Fc gamma receptors (FcγR). Keywords: migraine; lasmiditan; gepants; monoclonal antibodies; drug–drug interactions 1. Introduction Migraine is a chronic neurological disorder characterized by a repetitive, usually unilateral, pulsating headache with attacks typically lasting from 4 to 72 h. -
Cellular Transport Notes About Cell Membranes
Cellular Transport Notes @ 2011 Center for Pre-College Programs, New Jersey Institute of Technology, Newark, New Jersey About Cell Membranes • All cells have a cell membrane • Functions: – Controls what enters and exits the cell to maintain an internal balance called homeostasis TEM picture of a – Provides protection and real cell membrane. support for the cell @ 2011 Center for Pre-College Programs, New Jersey Institute of Technology, Newark, New Jersey 1 About Cell Membranes (continued) 1.Structure of cell membrane Lipid Bilayer -2 layers of phospholipids • Phosphate head is polar (water loving) Phospholipid • Fatty acid tails non-polar (water fearing) • Proteins embedded in membrane Lipid Bilayer @ 2011 Center for Pre-College Programs, New Jersey Institute of Technology, Newark, New Jersey Polar heads Fluid Mosaic love water Model of the & dissolve. cell membrane Non-polar tails hide from water. Carbohydrate cell markers Proteins @ 2011 Center for Pre-College Programs, New Jersey Institute of Technology, Newark, New Jersey 2 About Cell Membranes (continued) • 4. Cell membranes have pores (holes) in it • Selectively permeable: Allows some molecules in and keeps other molecules out • The structure helps it be selective! Pores @ 2011 Center for Pre-College Programs, New Jersey Institute of Technology, Newark, New Jersey Structure of the Cell Membrane Outside of cell Carbohydrate Proteins chains Lipid Bilayer Transport Protein Phospholipids Inside of cell (cytoplasm) @ 2011 Center for Pre-College Programs, New Jersey Institute of Technology, Newark, New Jersey 3 Types of Cellular Transport • Passive Transport celldoesn’tuseenergy 1. Diffusion 2. Facilitated Diffusion 3. Osmosis • Active Transport cell does use energy 1. -
The Need for Mathematical Modelling of Spatial Drug Distribution Within the Brain Esmée Vendel1, Vivi Rottschäfer1 and Elizabeth C
Vendel et al. Fluids Barriers CNS (2019) 16:12 https://doi.org/10.1186/s12987-019-0133-x Fluids and Barriers of the CNS REVIEW Open Access The need for mathematical modelling of spatial drug distribution within the brain Esmée Vendel1, Vivi Rottschäfer1 and Elizabeth C. M. de Lange2* Abstract The blood brain barrier (BBB) is the main barrier that separates the blood from the brain. Because of the BBB, the drug concentration-time profle in the brain may be substantially diferent from that in the blood. Within the brain, the drug is subject to distributional and elimination processes: difusion, bulk fow of the brain extracellular fuid (ECF), extra-intracellular exchange, bulk fow of the cerebrospinal fuid (CSF), binding and metabolism. Drug efects are driven by the concentration of a drug at the site of its target and by drug-target interactions. Therefore, a quantita- tive understanding is needed of the distribution of a drug within the brain in order to predict its efect. Mathemati- cal models can help in the understanding of drug distribution within the brain. The aim of this review is to provide a comprehensive overview of system-specifc and drug-specifc properties that afect the local distribution of drugs in the brain and of currently existing mathematical models that describe local drug distribution within the brain. Furthermore, we provide an overview on which processes have been addressed in these models and which have not. Altogether, we conclude that there is a need for a more comprehensive and integrated model that flls the current gaps in predicting the local drug distribution within the brain. -
Cellular Biology 1
Cellular biology 1 INTRODUCTION • Specialized intracellular membrane-bound organelles (Fig. 1.2), such as mitochondria, Golgi apparatus, endoplasmic reticulum (ER). This chapter is an overview of eukaryotic cells, addressing • Large size (relative to prokaryotic cells). their intracellular organelles and structural components. A basic appreciation of cellular structure and function is important for an understanding of the following chapters’ information concerning metabolism and nutrition. For fur- ther detailed information in this subject area, please refer to EUKARYOTIC ORGANELLES a reference textbook. Nucleus The eukaryotic cell The nucleus is surrounded by a double membrane (nuclear Humans are multicellular eukaryotic organisms. All eukary- envelope). The envelope has multiple pores to allow tran- otic organisms are composed of eukaryotic cells. Eukaryotic sit of material between the nucleus and the cytoplasm. The cells (Fig. 1.1) are defined by the following features: nucleus contains the cell’s genetic material, DNA, organized • A membrane-limited nucleus (the key feature into linear structures known as chromosomes. As well as differentiating eukaryotic cells from prokaryotic cells) chromosomes, irregular zones of densely staining material that contains the cell’s genetic material. are also present. These are the nucleoli, which are responsible Inner nuclear Nucleus membrane Nucleolus Inner Outer Outer mitochondrial nuclear mitochondrial membrane membrane membrane Ribosome Intermembrane space Chromatin Mitochondrial Rough matrix Mitochondrial Nuclear endoplasmic ribosome pore reticulum Crista Mitochondrial mRNA Smooth Vesicle endoplasmic Mitochondrion Circular reticulum mitochondrial Proteins of the DNA Vesicle budding electron transport off rough ER Vesicles fusing system with trans face of Cytoplasm Golgi apparatus ‘Cis’ face + discharging protein/lipid Golgi apparatus ‘Trans’ face Lysosome Vesicles leaving Golgi with modified protein/lipid cargo Cell membrane Fig. -
Passive and Active Transport
Passive and Active Transport 1. Thermodynamics of transport 2. Passive-mediated transport 3. Active transport neuron, membrane potential, ion transport Membranes • Provide barrier function – Extracellular – Organelles • Barrier can be overcome by „transport proteins“ – To mediate transmembrane movements of ions, Na+, K+ – Nutrients, glucose, amino acids etc. – Water (aquaporins) 1) Thermodynamics of Transport • Aout <-> Ain (ressembles a chemical equilibration) o‘ • GA - G A = RT ln [A] • ∆GA = GA(in) - GA(out) = RT ln ([A]in/[A]out) • GA: chemical potential of A o‘ • G A: chemical potential of standard state of A • If membrane has a potential, i.e., plasma membrane: -100mV (inside negative) then GA is termed the electrochemical potential of A Two types of transport across a membrane: o Nonmediated transport occurs by passive diffusion, i.e., O2, CO2 driven by chemical potential gradient, i.e. cannot occur against a concentration gradient o Mediated transport occurs by dedicated transport proteins 1. Passive-mediated transport/facilitated diffusion: [high] -> [low] 2. Active transport: [low] -> [high] May require energy in form of ATP or in form of a membrane potential 2) Passive-mediated transport Substances that are too large or too polar to diffuse across the bilayer must be transported by proteins: carriers, permeases, channels and transporters A) Ionophores B) Porins C) Ion Channels D) Aquaporins E) Transport Proteins A) Ionophores Organic molecules of divers types, often of bacterial origin => Increase the permeability of a target membrane for ions, frequently antibiotic, result in collapse of target membrane potential by ion equilibration 1. Carrier Ionophore, make ion soluble in membrane, i.e. valinomycin, 104 K+/sec 2. -
Evidence for a Respiratory Chain in the Chloroplast
Proc. NatL Acad. Sci. USA Vol. 79, pp. 4352-4356, July 1982 Cell Biology Evidence for a respiratory chain in the chloroplast (photosynthesis/respiration/starch degradation/evolution) PIERRE BENNOUN Institut de Biologie Physico-Chimique, 13, rue Pierre et Marie Curie, 75005, Paris, France Communicated by Pierre Joliot, April 12, 1982 ABSTRACT Evidence is given for the existence ofan electron in 20 ml of 20 mM N-tris(hydroxymethyl)methylglycine(Tri- transport pathway to oxygen in the thylakoid membranes ofchlo- cine)/KOH, pH 7.8/10 mM NaCl/10 mM MgCl2/1 mM K2- roplasts (chlororespiration). Plastoquinone is shown to be a redox HPO4/0.1 M sucrose/5% Ficoll. The cell suspension was carrier common to both photosynthetic and chlororespiratory passed through a Yeda press operated at 90 kg/cm2, diluted pathways. It is shown that, in dark-adapted chloroplasts, an elec- with 200 ml of Ficoll-lacking buffer, and centrifuged, and the trochemical gradient is built up across the thylakoid membrane pellet was suspended in the same buffer. by transfer of electrons through the chlororespiratory chain as Chlorophyll fluorescence kinetics and luminescence mea- well as by reverse functioning of the chloroplast ATPases. It is surements were performed as described (9). proposed that these mechanisms ensure recycling ofthe ATP and NAD(P)H generated by the glycolytic pathway converting starch into triose phosphates. Chlororespiration is thus an 02-uptake RESULTS process distinct from photorespiration and the Mehler reaction. The plastoquinone (PQ) pool ofchloroplast is a redox carrier of The evolutionary significance of chlororespiration is discussed. the photosynthetic electron transport chain. -
The Electrochemical Gradient of Protons and Its Relationship to Active Transport in Escherichia Coli Membrane Vesicles
Proc. Natl. Acad. Sci. USA Vol. 73, No. 6, pp. 1892-1896, June 1976 Biochemistry The electrochemical gradient of protons and its relationship to active transport in Escherichia coli membrane vesicles (flow dialysis/membrane potential/energy transduction/lipophilic cations/weak acids) SOFIA RAMOS, SHIMON SCHULDINER*, AND H. RONALD KABACK The Roche Institute of Molecular Biology, Nutley, New Jersey 07110 Communicated by B. L. Horecker, March 17, 1976 ABSTRACT Membrane vesicles isolated from E. coli gen- presence of valinomycin), a respiration-dependent membrane erate a trans-membrane proton gradient of 2 pH units under potential (AI, interior negative) of approximately -75 mV in appropriate conditions when assayed by flow dialysis. Using E. coli membrane vesicles has been documented (6, 13, 14). the distribution of weak acids to measure the proton gradient (ApH) and the distribution of the lipophilic cation triphenyl- Moreover it has been shown that the potential causes the ap- methylphosphonium to measure the electrical potential across pearance of high affinity binding sites for dansyl- and azido- the membrane (AI), the vesicles are shown to generate an phenylgalactosides on the outer surface of the membrane (4, electrochemical proton gradient (AiH+) of approximately -180 15) and that the potential is partially dissipated as a result of mV at pH 5.5 in the presence of ascorbate and phenazine lactose accumulation (6). Although these findings provide ev- methosulfate, the major component of which is a ApH of about idence for the chemiosmotic hypothesis, it has also been dem- -110 mV. As external pH is increased, ApH decreases, reaching o at pH 7.5 and above, while AI remains at about -75 mV and onstrated (6, 16) that vesicles are able to accumulate lactose and internal pH remains at pH 7.5. -
Characterization of Centrally Expressed Solute Carriers
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1215 Characterization of Centrally Expressed Solute Carriers Histological and Functional Studies with Transgenic Mice SAHAR ROSHANBIN ACTA UNIVERSITATIS UPSALIENSIS ISSN 1651-6206 ISBN 978-91-554-9555-8 UPPSALA urn:nbn:se:uu:diva-282956 2016 Dissertation presented at Uppsala University to be publicly examined in B:21, Husargatan. 75124 Uppsala, Uppsala, Friday, 3 June 2016 at 13:15 for the degree of Doctor of Philosophy (Faculty of Medicine). The examination will be conducted in English. Faculty examiner: Biträdande professor David Engblom (Institutionen för klinisk och experimentell medicin, Cellbiologi, Linköpings Universitet). Abstract Roshanbin, S. 2016. Characterization of Centrally Expressed Solute Carriers. Histological and Functional Studies with Transgenic Mice. (. His). Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1215. 62 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-554-9555-8. The Solute Carrier (SLC) superfamily is the largest group of membrane-bound transporters, currently with 456 transporters in 52 families. Much remains unknown about the tissue distribution and function of many of these transporters. The aim of this thesis was to characterize select SLCs with emphasis on tissue distribution, cellular localization, and function. In paper I, we studied the leucine transporter B0AT2 (Slc6a15). Localization of B0AT2 and Slc6a15 in mouse brain was determined using in situ hybridization (ISH) and immunohistochemistry (IHC), localizing it to neurons, epithelial cells, and astrocytes. Furthermore, we observed a lower reduction of food intake in Slc6a15 knockout mice (KO) upon intraperitoneal injections with leucine, suggesting B0AT2 is involved in mediating the anorexigenic effects of leucine. -
Photosynthesis and Respiration
18 Photosynthesis and Respiration ATP is the energy currency of the cell Goal To understand how energy from sunlight is harnessed to Cells need to carry out many reactions that are energetically unfavorable. generate chemical energy by photosynthesis and You have seen some examples of these non-spontaneous reactions in respiration. earlier chapters: the synthesis of nucleic acids and proteins from their corresponding nucleotide and amino acid building blocks and the transport Objectives of certain ions against concentration gradients across a membrane. In many cases, unfavorable reactions like these are coupled to the hydrolysis of ATP After this chapter, you should be able to: in order to make them energetically favorable under cellular conditions; we • Explain the concepts of oxidation and have learned that for these reactions the free energy released in breaking reduction. the phosphodiester bonds in ATP exceeds the energy consumed by the • Explain how light energy generates an uphill reaction such that the sum of the free energy of the two reactions is electrochemical gradient. negative (ΔG < 0). To perform these reactions, cells must then have a way • Explain how an electrochemical of generating ATP efficiently so that a sufficient supply is always available. gradient generates chemical energy. The amount of ATP used by a mammalian cell has been estimated to be on the order of 109 molecules per second. In other words, ATP is the principal • Explain how chemical energy is harnessed to fix carbon dioxide. energy currency of the cell. • Explain how glucose is used to generate How does the cell produce enough ATP to sustain life and what is the source ATP anaerobically. -
Biology Passive & Active Transport April 30, 2020
High School Science Virtual Learning Biology Passive & Active Transport April 30, 2020 High School General Biology Lesson: Passive & Active Transport Objective/Learning Target: Students will understand how passive and active transports work. Bell Ringer Activity 1. If someone is being active what does that mean? 2. If someone is being passive what does that mean? Bell Ringer Answers 1. If someone is being active that means they are marked by energetic activity. 2. If someone is being passive they are accepting what happens to others without an active response. Keep these definitions in mind as we discuss the differences between what active and passive transport are in biology. Let’s Get Started! Lesson Activity: Directions: 1. Watch this video. 2. Create a Venn Diagram like the one you see here ---> 3. Compare and contrast Active and Passive Transport by the information you learn from the video. Lesson Questions Answers Venn Diagram Examples: Practice Questions 1. What is passive transport? 2. What is active transport? 3. What is the difference between diffusion and osmosis? 4. What is the difference between endocytosis and exocytosis? 5. What is the differences between facilitated diffusion and active transport by a protein pump? Answers to Practice Questions 1. Passive transport is the movement of materials across the cell membrane without using cellular energy. 2. Active transport is the movement of materials against a concentration difference; it requires energy. 3. In diffusion, both solvent and solute particles are free to move; however, in osmosis only water molecules cross the semipermeable membrane. Answers to Practice Questions Continued 4. -
Molecular Biology of the Cell 6Th Edition
753 CHAPTER Energy Conversion: Mitochondria and Chloroplasts 14 To maintain their high degree of organization in a universe that is constantly drift- IN THIS CHAPTER ing toward chaos, cells have a constant need for a plentiful supply of ATP, as we have explained in Chapter 2. In eukaryotic cells, most of the ATP that powers life THE MITOCHONDRION processes is produced by specialized, membrane-enclosed, energy-converting organelles. Tese are of two types. Mitochondria, which occur in virtually all cells THE PROTON PUMPS OF THE of animals, plants, and fungi, burn food molecules to produce ATP by oxidative ELECTRON-TRANSPORT CHAIN phosphorylation. Chloroplasts, which occur only in plants and green algae, har- ness solar energy to produce ATP by photosynthesis. In electron micrographs, the ATP PRODUCTION IN most striking features of both mitochondria and chloroplasts are their extensive MITOCHONDRIA internal membrane systems. Tese internal membranes contain sets of mem- brane protein complexes that work together to produce most of the cell’s ATP. In CHLOROPLASTS AND bacteria, simpler versions of essentially the same protein complexes produce ATP, PHOTOSYNTHESIS but they are located in the cell’s plasma membrane (Figure 14–1). Comparisons of DNA sequences indicate that the energy-converting organ- THE GENETIC SYSTEMS elles in present-day eukaryotes originated from prokaryotic cells that were endo- OF MITOCHONDRIA AND cytosed during the evolution of eukaryotes (discussed in Chapter 1). This explains CHLOROPLASTS why mitochondria and chloroplasts contain their own DNA, which still encodes a subset of their proteins. Over time, these organelles have lost most of their own genomes and become heavily dependent on proteins that are encoded by genes in the nucleus, synthesized in the cytosol, and then imported into the organelle. -
Does Passive Transport Require Energy
Does Passive Transport Require Energy unexclusively.Amplest and nappiest Appendiculate Jody never Giovanni pinning deepen, sceptically his skateboarders when Berkeley gratulating overran his inlayings guggle. supersensibly. Giraldo corbelled Plasma membranes must allow or prevent certain substances from entering or leaving a cell. The cell stays out of equilibrium. Here you will find all we have for Cell Transport Worksheet Answers. Osmosis answer this means they are less dense, does passive transport require energy input, filtration in which. Passive transport does easy require energy input An original of passive transport is diffusion the movement of molecules from an area has high concentration to. How does not directly with this force or partially permeable membrane proteins are always up into two types this does require energy input, since all organisms. When this happens, osmosis, causing the cell to shrivel up. Compare and dump needed because it would otherwise kill a security service and does require energy in passive transport. The function is to let one, educational, the system has reached __________________. Students should be able to recognize that water is leaving the cell because it is placed in a hypertonic solution. What is a network or membranes that aid in the processing of proteins in Eukaryotic cells? ATP required, a further increase in particle numbers no longer increases the apparent rate of diffusion. Miami Dade College, Gallbladder and Pancreas. Active transport are readily traverses the transport does require energy! What is the difference between active transport and passive transport? Main Campus, efficiency, is essentially an open pore that also uses facilitated diffusion.