Biological Sciences

Primary Active Transport

Primary active transport is a process in which molecules are transported across a cell membrane against their concentration gradient, requiring the direct input of energy, usually in the form of ATP. This transport mechanism is essential for maintaining proper ion concentrations and electrochemical gradients within cells, and is carried out by specific membrane-bound protein pumps, such as the sodium-potassium pump.

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12 Key excerpts on "Primary Active Transport"

  • Book cover image for: Human Physiology
    eBook - PDF
    • Bryan H. Derrickson(Author)
    • 2019(Publication Date)
    • Wiley
      (Publisher)
    The most prevalent Primary Active Transport mechanism expels sodium ions (Na + ) from cells and brings potassium ions 146 CHAPTER 5 Transport Across the Plasma Membrane Na + electrochemical gradient to move a solute against its concentration gradient from extracellular fluid to the cytosol (Figure 5.17): 1 A Na + ion binds to a Na + binding site on the extracellular side of the carrier protein. 2 Binding of Na + causes the solute binding site to increase its affinity, which promotes binding of a solute molecule in extracellular fluid. 3 Binding of the solute causes a conformational change in the carrier protein, exposing both the Na + binding site and the solute binding site to the cytosol. 4 Na + dissociates from the carrier protein and moves into the cytosol down its electrochemical gradient. The release of Na + decreases the affinity of the solute binding site, resulting in release of the solute. The solute then enters the cytosol, moving against its concentration gradient. As you have just learned, in secondary active transport, a carrier protein binds to Na + and another solute and then changes its conformation so that both solutes cross the mem- brane at the same time. If these transporters move two solutes in the same direction, they are called symporters (sym- = same); antiporters, by contrast, move two solutes in opposite directions across the membrane (anti- = against). Secondary Active Transport Uses Energy from an Ionic Gradient to Move a Solute Against Its Gradient In secondary active transport, the energy stored in an ionic electrochemical gradient is used to drive other solutes across the membrane against their own concentration or electro- chemical gradients. Most secondary active transport systems are driven by the Na + electrochemical gradient. Because a Na + gradient is established by Primary Active Transport, secondary active transport indirectly uses energy obtained from the hydrolysis of ATP.
  • Book cover image for: The Movement Of Molecules Across Cell Membranes
    C H A P T E R 6 The Primary Active Transport Systems 6.1 Criteria for Distinguishing between Primary and Secondary Active Transport Systems A simple yet sufficient criterion of the existence of an active transport system is that the following condition b e satisfied: A net flux of the permeant must occur in a direction opposite to that of the electrochemical gradient of the transferred species (Section 2 . 7 ) . In Chapter 5 w e saw that many active transports arise as a result of the co-transport of a metabolite together with sodium ions. T h e linking of the fluxes of the metabolite and the sodium ions results from the requirement that both these species must be attached to the mobile membrane carrier if transport is to occur. Thus the force driving the flux of sodium ions (the electrochemical gradient of sodium) indirectly drives by co-transport the flux of metabolite. W e have seen, too (Section 5 . 5 ) , that by counter-transport the active transport of a third species can b e linked by two stages with the electrochemical gradient of sodium ions. It is conceivable that all active transport in a cell might occur by such secondary and tertiary transports, the fundamental concentration gradient arising per-haps from the continual intracellular depletion of some cell constituent by metabolic activity. L e t us consider how we could distinguish between this situation and a true case of primary transport. W e begin by considering the possible forces that can drive a net flux. In Section 2.8 we saw how it was possible to consider Ji the flux of the ith component as resulting from ( 1 ) the electrochemical gradient in i i t s e l f : — Δ /Λ ί? · or ( 2 ) an interaction with the flux J } of some other com-ponent or ( 3 ) the action of some chemical reaction J r . Formally, we can write η Ji = Ra Αμΐ + ^RijJj + RirJr (6 -1) .7 = 0 207 208 6. THE Primary Active Transport SYSTEMS where the interaction coefficients are the respective terms R.
  • Book cover image for: Transport in Biological Media
    • Sid M. Becker, Andrey V. Kuznetsov, Sid Becker, Andrey Kuznetsov(Authors)
    • 2013(Publication Date)
    • Elsevier
      (Publisher)
    Chapter 5

    Carrier-Mediated Transport Through Biomembranes

    Ranjan K. Pradhan, Kalyan C. Vinnakota, Daniel A. Beard and Ranjan K. Dash,    Biotechnology and Bioengineering Center and Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA

    Acknowledgment

    This work was partially supported by the National Institute of Health grants R01-HL095122 (RKD) and P50-GM094503 (DAB).

    5.1 Introduction

    Biological membranes are composed of phospholipid bilayers, which act as a selective barrier within or around a cell [1] . Transporters or carriers are specialized proteins spanning the phospholipid bilayer that facilitate the translocation of ions, metabolites and macromolecules across the membrane. Transport processes are usually classified as active (primary or secondary) or passive transport [2] . Primary Active Transport involves the movement of a solute against its electrochemical gradient facilitated by coupling to a process that provides the required free energy, e.g., pump driven by ATP hydrolysis, whereas passive transport is always driven by the solute electrochemical gradient. Secondary active transport is also commonly known as ion-coupled solute transport, and is where the electrochemical gradient of an ion maintained by an active transport process is utilized to transport a different solute. This is another commonly observed mode of transport in biological membrane systems (e.g., -glucose cotransporter [3] , -monocarboxylate cotransporter [4] and exchanger [5]
  • Book cover image for: Molecular Pharmacology
    eBook - ePub

    Molecular Pharmacology

    From DNA to Drug Discovery

    • John Dickenson, Fiona Freeman, Chris Lloyd Mills, Christian Thode, Shiva Sivasubramaniam, Christian Thode(Authors)
    • 2012(Publication Date)
    • Wiley
      (Publisher)
    Figure 5.1 ).
    Figure 5.1
    Diagram showing how the primary and secondary energy sources are generated for tertiary active transport of organic anions into renal cells. Na+ ions are pumped out of the cell using the Na+ /K+ pump with energy derived from the breakdown of ATP (Primary Active Transport). This results in a higher extracellular concentration of Na+ ions. Dicarboxylate (DC) is transported into the cell via the Na+ /DC symporter using the co-transportation of Na+ ions down its concentration gradient as the source of energy (secondary active transport). The DC gradient is then used to import organic anions (OA) into the cell using the OA/DC antiporter.

    5.2 Classification

    Transporters can be classified in the same way as enzymes, based on their mechanism of action, what they carry and their structure, with the classification continually being updated as more information about transporters emerges (http://www.tcdb.org ; Saier et al., 2009). In this chapter we will concentrate on the major groups involved in pathophysiology and drug discovery.
    Table 5.1 shows the major classes and their subclasses of transporter. Channels and Pores (Figure 5.2 ) constitute the first class of transporters and until recently they were not really considered to be transporters because they form an open link between cellular compartments from which ions or small molecules can diffuse from a region of high- to one of low- concentration. However, the presence of hydrophobic, hydrophilic and amphipathic groups inside the pore/channel allow them to selectivly facilitate trans-membrane ion and small molecule movement which is a characteristic of transporters. Whilst pores are continually open (un-gated channel), channels can be open or closed (gated pore). This is a large family that includes ionotrophic and voltage-gate receptors which have an integral channel that upon activation results in its opening, ion channels that are gated by second messengers (e.g. IP3
  • Book cover image for: Cell-Associated Water
    eBook - PDF

    Cell-Associated Water

    Proceedings of a Workshop on Cell-Associated Water Held in Boston, Massachusetts, September, 1976

    • W. Drost-Hansen, James S. Clegg, W. Drost-Hansen, James S. Clegg(Authors)
    • 2013(Publication Date)
    • Academic Press
      (Publisher)
    Cell-Associated Water METABOLIC CONTROL OF THE PROPERTIES OF INTRACELLULAR WATER AS A UNIVERSAL DRIVING FORCE FOR ACTIVE TRANSPORT^ Philippa M. Wiggins Department of Medicine University of Auckland School of Medicine Auckland, New Zealand I. INTRODUCTION Over the last few years an attempt has been made to de-velop an hypothesis of energy conservation as adenosinetri-phosphate (ATP), and its use for active transport, which is simple, universal and yet sufficiently versatile to be able to account for the wide diversity of transport processes. The hypothesis ascribes to water a central role in many cellular processes, and requires that both its structure and its solvent properties be under some degree of metabolic control (1,2,3). Active transport is defined initially as an energy-dependent movement of an ion (or other solute) against a real or apparent electrochemical potential gradient. For example, most cells loaded with Na* will, in the presence of energy, expel Na* ions against a concentration gradient until a steady state is reached. In the case of muscle, for example, the apparent concentration of intracellular Na^ is about 25 Mole · m^, and that of extracellular Na* about 145 Mole · m^, while the potential difference across the mem-brane is -90 mV (inside negative relative to outside). In the absence of energy, on the other hand, muscle cells ^This work was carried out during the tenure of a Career Fellowship of the Medical Research Council of New Zealand. Copyright © 1979 by Academic Press, Inc. All rights of reproduction in any form reserved. ISBN 0-12-222250-4 jQ Philippa Μ. Wiggins continue to take up Na* until the intracellular concentra-tion is higher than the extracellular concentration, and the membrane potential is quite low, but still negative in-side relative to outside.
  • Book cover image for: Nuclear Trafficking
    Clearly, active transport mechanisms, that is, moving a substance against its chemical gradient, would be dependent on coupling to the decrease in free energy of some metabolic process. In general, energy coupling to any of the four steps in the cyclic-process carrier-type envelope transport mechanisms would be both sufficient and feasible. However, as mentioned previously, a re-quirement for ATP hydrolysis does not itself constitute proof that active trans-port is occurring. For example, facilitated diffusion of large molecules, in particular those with diameters > 90-100 Â, through the NPC requires an energy source to elicit requisite conformational changes in the transportant and/or NPC proteins. Finally, one or more energy-requiring steps may be needed to process a molecule or its receptor(s), even when energy is not used to drive envelope transport per se. For instance, nuclear accumulation follow-ing envelope transit could require ATP hydrolysis if intranuclear retention by association is energy dependent. Rapid ATP-dependent intranuclear degrada-tion of specific proteins could result in continuous nuclear influx by simple diffusion. There are two general types of coupling: primary and secondary. Primary Active Transport uses the direct coupling of an energy-producing reaction, such as nucleo-side triphosphate hydrolysis, to drive transport. This transport may involve a conformational change of a protein carrier or channel. Alternatively, a group translocation may operate in which energy is used to covalently bind a chemical group such as a phosphate to the transportant. The group may be released with a decrease in free energy some time after transport. A rapidly increasing body of evidence implicates reversible phosphorylation/dephosphorylation in the nuclear accumulation of specific N-proteins. Secondary active transport couples the active uphill transport of one sub-stance to the downhill transport of a second, the driver.
  • Book cover image for: A Modern Course in Transport Phenomena
    24 Transport in Biological Systems Life depends on transport. In this chapter, we discuss molecular motors and ion pumps, which perform key functions in living organisms. Both examples of molecular machines are based on activated transport, that is, transport enabled by the energy provided by a chemical reaction, typically the hydrol-ysis of adenosine triphosphate (ATP). Molecular motors convert chemical energy into mechanical work (such as locomotion, carrying around stuff in cells); ion pumps transport ions against concentration gradients. In both cases, our goal is to develop kinetic theories to predict phenomenological transport coefficients from more microscopic descriptions. Both kinetic the-ories are based on stochastic equations. For ion pumps, we rely on a diffusion equation introduced in Chapter 2 and repeatedly occurring ever since. For molecular motors, we rely on a master equation as a useful new tool. 24.1 Molecular Motors Purposeful movement is one of the characteristics of living organisms. This ability is based on molecular motors that convert chemical into mechani-cal energy. Indeed, molecular motors are the key to active transport , which keeps living organisms away from deadly equilibrium. Our description and modeling of such tiny machines is strongly influenced by Chapter 16 of the comprehensive textbook entitled Physical Biology of the Cell by Phillips, Kondev, and Theriot. 1 Transport of ions through cell membranes against ion concentration gra-dients, already mentioned for motivation in Section 1.1 , provides an example of active transport. Even large molecules, such as proteins, nucleic acids, sug-ars, or lipids, can be pushed or pulled through holes in membranes, which is typically achieved by translocation motors . In the present chapter, however, 1 Phillips et al ., Physical Biology of the Cell (Garland Science, 2009). 416 Transport in Biological Systems we rather focus on translational motors .
  • Book cover image for: Cell Boundaries
    eBook - ePub

    Cell Boundaries

    How Membranes and Their Proteins Work

    • Stephen White, Gunnar von Heijne, Donald Engelman, Stephen H White, Donald M Engelman(Authors)
    • 2021(Publication Date)
    • Garland Science
      (Publisher)
    Chapter 13 .
    How are ion and solute pumping coupled to ATP consumption in primary transporters? We first examine the family of P-type ATPases, and in particular the Na+ /K+ -ATPase, responsible for establishing the transmembrane electrochemical gradient of axons and other cells, and the Ca2+ -ATPase that maintains strong Ca2+ gradients across the muscle sarcoplasmic reticulum as an essential feature of the control of muscle contraction. We then consider another very large family of proteins, the so-called ATP binding cassette (ABC) transporters, which use ATP for pumping all sorts of molecules across cell membranes. Finally, we consider an interesting family of ATP-driven transporters, the energy-coupling factor (ECF) transporters, in which the substrate-binding subunit appears to “topple” in the membrane in response to ATP hydrolysis.

    12.1 P-Type ATPases

    P-type ATPases are found throughout the living world. P-type ATPases actively transport a variety of ions—and even lipids—across membranes. The name is meant to reflect a key mechanistic feature, namely, that a conserved Asp residue is phosphorylated during the reaction cycle. All P-type ATPases have five domains that cooperate during the reaction cycle: the cytoplasmic actuator (A), nucleotide-binding (N), and phosphorylation (P) domains, and the two membrane-embedded transport (T) and class-specific support (S) domains (Figure 12.2 ). In many cases, there is also a sixth regulatory (R) domain attached to the N- or C-terminus (or both) of the protein. We will focus the discussion on two P-type ATPases: the historically important Na+ /K+ -ATPase and the currently best understood P-type ATPase, the Ca2+
  • Book cover image for: Exploring the Cell Membrane: Conceptual Developments
    ATPases of the 'P type appear to have developed later in response to the requirements of ionic homeostasis in cells, offering greater versatility as to ionic specificity (J0rgensen and Andersen, 1988). 2. TOWARDS THE MECHANISM OF THE SECONDARY ACTIVE SOLUTE TRANSPORT The use of membrane vesicles prepared from epithelial cells, first introduced by Miller and Crane (1961), permitted clarifi-cation of the mechanism of transport processes in more detail since in such preparations substrate metabolism is eliminated 22 Such concept would have been welcomed by Mitchell as an additional argument in favor of the protonmotive force as the primary driving force (see Chapter 6). THE CONCEPT OF A SOLUTE PUMP 169 due to a loss of intracellular enzymes; effects of ionic and sub-strate gradients can also be studied. Preparations derived from either the brush-border, or the basolateral membranes {cf Kinne, 1976) permit the definition of the cellular localiza-tion of the transport. Membrane vesicles made it possible to provide convincing evidence in favor of the gradient hypothesis as the mecha-mism for the secondary active transport of organic solutes, as shown at the Symposium of the New York Academy of Sci-ences (Semenza and Kinne, 1985). Since the brush-border ves-icles of epithelial cells are impoverished in the Na + -extruding mechanism, the imposition of a Na + gradient outside > inside produced an uphill flux of glucose (phlorizin-inhibitable) or of amino acids in the vesicles; the accumulation of the organic solutes was abolished when the Na + gradient was dissipated (Kinne, 1976). The predicted electrogenicity of the NaVglucose cotransport system was then established by Murer and Hopfer (1974). On the other hand, vesicles derived from the baso-lateral membrane did not display the NaVglucose cotransport system, but showed a high concentration of the (Na + -K + )-ATP-ase.
  • Book cover image for: Channels, Carriers, and Pumps
    eBook - PDF

    Channels, Carriers, and Pumps

    An Introduction to Membrane Transport

    • Wilfred D. Stein(Author)
    • 2012(Publication Date)
    • Academic Press
      (Publisher)
    Hence, the cycling of the calcium pump in the direction of removal of calcium from the cytoplasm is favored. This pump is, again, reversible, and ATP synthesis from ADP and Pj will occur when levels of calcium are such as to favor this direction of cycling. It is the strict coupling of calcium transport and ATP splitting that drives transport. The fact that the calcium pump changes its affinity from high to low as it alters confor-mation from Ei (with binding sites facing the cytoplasm) to E 2 (with binding sites facing the lumen of the vesicle) speeds up the transport of calcium but is not the force that drives it. 244 6. Primary Active Transport Systems 6.3. THE CALCIUM PUMP OF THE PLASMA MEMBRANE The sodium-calcium antiporter, discussed in detail in Section 5.2.5, is only one of the systems by which the cytoplasmic concentration of cal-cium ions in the cell is kept low. The other method is the harnessing of Primary Active Transport by the calcium-activated ATPase of the plasma membrane, a system first identified by Hans Schatzmann. Such a primary transporter of calcium ions is present in the plasma membrane of most animal cells. Two well-studied systems are those of red blood cells and the nerve membrane. The system in the human red blood cell is very effective. With cells stored in their own plasma, at a free calcium concen-tration of 1.3 mM, the intracellular free calcium can be as low as 26 nM, a 50,000-fold concentration ratio. The transmembrane potential in these red cells is about 10 mV, so that efflux of a divalent cation is hindered by the inside negative potential by a factor of 2.25-fold (59 mV is equivalent to a 100-fold concentration ratio for a divalent cation; see Section 2.2).
  • Book cover image for: Bioelectrochemistry of Biomembranes and Biomimetic Membranes
    • Rolando Guidelli(Author)
    • 2016(Publication Date)
    • Wiley
      (Publisher)
    129 5 Active Transport 5.1 The Ion Pumps Only a limited number of integral proteins, called ion pumps, have the ability to couple an exergonic chemical or photochemical reaction to a flow of ions across a membrane against their electrochemical potential gradient. This coupling of a scalar process (the chemical or photochemical reaction) to a vectorial process (the ion translocation) can only take place in a heterogeneous system provided by a biological membrane interposed between its interior and exterior solutions. Only some inorganic ions, such as Na + , K + , Ca 2 + , and H + , are translocated specifically by the ion pumps. Ion pumps can be subdivided into three classes: (i) ATPases; (ii) enzymes of the electron-transport chain, which translocate protons; and (iii) light-driven proton pumps, such as bacteriorhodopsin (Läuger, 1991). ATPases are integral membrane proteins that couple the exergonic reaction of hydrolysis of ATP into ADP and free phosphate ion (P i ) to the endergonic trans-port of an ion across a membrane against its electrochemical potential gradient. This coupling is widely used in all known forms of life. There are different types of ATPases, which differ in function (ATP synthesis and/or hydrolysis), structure, and type of transported ion. They can be classified into P-type, F-type, V-type, and A-type ATPases. P-type ATPases, also known as E 1 –E 2 ATPases, are a large group of evolution-arily related ion pumps that are found in bacteria, archaea, and eukaryotes. They are referred to as P-type ATPases because they catalyze phosphorylation of a key conserved aspartate residue within the pump by ATP. Vanadate, a transition-state analog of phosphate, inhibits this reaction, since it competes with phosphate for the specific binding site in the ion pump, preventing its phosphorylation.
  • Book cover image for: Intestinal Absorption of Metal Ions, Trace Elements and Radionuclides
    • S. C. Skoryna, D. Waldron-Edward, S. C. Skoryna, D. Waldron-Edward(Authors)
    • 2013(Publication Date)
    • Pergamon
      (Publisher)
    It is evident that in any animal cell which subserves the function of translocation, the occurrence of some form of cytoplasmic streaming will transport and stir intracellular substrate. Although the occurrence of any orderly movement of the intracellular contents will require the expen-diture of energy and must ultimately add to the metabolic cost of translocation, Ewart has calculated that the energy expended in sustaining protoplasmic streaming must be relatively small. (48) The occurrence of such a process in absorbing cells would serve as yet another example of the wide and fascinating variety of phenomena which challenge workers in the fields of biological transport and intestinal absorption. The response of the investigator to this challenge is to direct his thoughts, ingenuity and efforts towards devising experimental procedures to test his views of the phenomenon. At least one outcome of such experiments can be predicted; many more problems will arise, each yet another challenge to the inves-tigator. Summary 1. A description is given of the properties of some model systems for the transcellular active transport ('translocation') of material across a single layer of epithelial cells. 2. The functioning of the models depends upon the occurrence of solute ('substrate') pumping across the bordering membranes of a unit cell, the membranes being also leaky to the substrate. Two types of system are specified. In one sort the limiting membranes of the unit cell are furnished with 'pumps' which move substrate into the cell so that the intra-cellular electrochemical potential of the substrate is maintained at a value greater than that outside and translocation is achieved by the movement of substrate passively out of the cell down leaks.
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