1 Transport Across Cell Membrane - I
2 Overview Introduction: Membrane overview Basic Mechanism of transport Passive transport Active transport Special categories of transport: Vesicular transport – Bulk flow – Endocytosis – Transcytosis
3 Introduction Structure of the cell membrane Cell membrane is composed of three types of substances: 1. Proteins (55%) 2. Lipids (40%) 3. Carbohydrates (5%).
4 Protein Layers of the Cell Membrane electron-dense layers in Electron microscopy These layers cover the two surfaces of the central lipid layer, giving protection to the central lipid layer. The protein substances present in these layers are mostly glycoproteins, classified as: 1. Integral proteins or trans-membrane proteins. 2. Peripheral proteins or peripheral membrane proteins.
5 Functions of Proteins in Cell Membrane Integral proteins provide the structural integrity to the cell membrane Channel proteins help in the diffusion of water-soluble substances like glucose and electrolytes Carrier or transport proteins help in the transport of substances across the cell membrane by means of active or passive transport Pump: Some carrier proteins act as pumps, by which ions are transported actively across the cell membrane
6 Functions of Proteins in Cell Membrane Receptor proteins serve as the receptor sites for hormones and neurotransmitters Enzymes: Some of the protein molecules form the enzymes and control chemical (metabolic) reactions within the cell membrane Antigens: Some proteins act as antigens and induce the process of antibody formation Cell adhesion molecules or the integral proteins are responsible for attachment of cells to their neighbors or to basal lamina
7 Lipid Layers of the Cell Membrane Bi-layered structure, centrally The characteristic feature of lipid layer is that, it is fluid in nature and not a solid structure Major lipids are: 1. Phospholipids 2. Cholesterol
8 Lipid Layers of the Cell Membrane Functions of Lipid Layer in Cell Membrane Lipid layer of the cell membrane is a semi-permeable membrane and allows only the fat-soluble substances to pass through it. Thus, the fat-soluble substances like O 2, CO 2 and Alcohol can pass through this lipid layer. The water-soluble substances such as glucose, urea and electrolytes cannot pass through this layer.
9 Carbohydrates of the Cell Membrane glycoproteins (proteoglycans) glycolipids Carbohydrate molecules form a thin and loose covering over the entire surface of the cell membrane called glycocalyx. Functions of Carbohydrates in Cell Membrance 1. Carbohydrate molecules are negatively charged and do not permit the negatively charged substances to move in and out of the cell 2. Glycocalyx from the neighboring cells helps in the tight fixation of cells with one another 3. Some carbohydrate molecules function as the receptors for some hormones.
10 FUNCTIONS OF CELL MEMBRANE 1.Protective function: Cell membrane protects the cytoplasm and the organelles present in the cytoplasm 2. Selective permeability: Cell membrane acts as a semi-permeable membrane, which allows only some substances to pass through it and acts as a barrier for other substances 3. Absorptive function: Nutrients are absorbed into the cell through the cell membrane 4. Excretory function: Metabolites and other waste products from the cell are excreted out through the cell membrane 5. Exchange of gases: Oxygen enters the cell from the blood and carbon dioxide leaves the cell and enters the blood through the cell membrane 6. Maintenance of shape and size of the cell: Cell membrane is responsible for the maintenance of shape and size of the cell.
11 Basic Mechanism of Transport Passive Transport Active Transport Passive Transport: Transport of substances along the concentration gradient or electrical gradient or both (electrochemical gradient). It is also known as diffusion or downhill movement. Here, the substances move from region of higher concentration to the region of lower concentration without need of energy: Diffusion
12 Types of Diffusion 1.Simple diffusion and 2.Facilitated diffusion. Simple diffusion of substances occurs either through lipid layer or protein layer of the cell membrane. Facilitated diffusion occurs with the help of the carrier proteins of the cell membrane. Thus, the diffusion can be discussed under three headings: 1. Simple diffusion through lipid layer 2. Simple diffusion through protein layer 3. Facilitated or carrier-mediated diffusion.
13 Simple diffusion through lipid layer The diffusion of lipid layer is directly proportional to solubility of substances in lipids Lipid layer of the cell membrane is permeable only to lipid-soluble substances like oxygen, carbon dioxide and alcohol
14 Simple diffusion through Protein Layer The protein layer of the membrane is permeable to water soluble substance Mainly electrolytes move through the protein layer through protein channels The channels contains pores for those substances which cannot pass through the lipid bi-layer
15 Types of protein channels Characteristic feature of protein channel is selective permeability Specific channels for specific ions, molecules are present. REGULATION OF THE CHANNELS Continuously Open channels = Ungated channels Closed channels/gated channels = open only when required
16 Types of Gated Channels Voltage Gated channels Ligand gated channels Mechanically gated channels
17 1.Voltage gated channels These channels open when there is change in electrical potential Eg. Neuromuscular Junction, Ca channels are open and move in the interior of the axon terminal;
18 2.Ligand gated channels These channels open in the presence of some hormonal substances (Ligands). Eg. Neuromuscular Junction the acetylcholine molecules cause opening of sodium channels in the postsynaptic membrane and sodium ions diffuse into the neuromuscular junction from ECF
19 Voltage gated channels and Ligand gated channels shown in Neuromuscular Junction (NMJ)
20 3.Mechanically gated channels Opened by some mechanical factors Eg. Channel present in the pressure receptors(Pacinian body) – Channels present in the hair cells in the internal ear.
21 Example of Mechanically Gated Channels: Hair cells in Inner Ear
22 Facilitated diffusion or Carrier Mediated Diffusion the water-soluble substances having larger molecules are transported by this way through the cell membrane with the help of a carrier protein. substances are transported faster than transport by simple diffusion. Eg, glucose, Amino acids: these molecules bind with carrier protein
23 Factors affecting rate of diffusion Permeability of cell membrane Temperature Concentration/electric gradient across the membrane Solubility of substance(lipid soluble: high) Thickness of cell membrane Size of molecules, ions Charge of ions
24 Special Types of Passive Transport 1.Filtration 2.Bulk flow 3.Osmosis
25 Special Types of Passive Transport FILTRATION Movement of water and solutes from an area of high hydrostatic pressure to an area of low hydrostatic pressure is called filtration. Eg. In kidneys, arterial end of blood vessels, etc
26 Special Types of Passive Transport BULK Flow/ Transport Bulk flow is the diffusion of large quantity of substances from a region of high pressure to the region of low pressure. It is due to the pressure gradient of the substance across the cell membrane. Eg. exchange of gases across the respiratory membrane in lungs
27 Special Types of Passive Transport OSMOSIS The movement of water or any other solvent from an area of lower concentration to an area of higher concentration of a solute, through a semi-permeable membrane occurs whenever there is a difference in the solute concentration on either side of the membrane. Osmosis depends upon osmotic pressure.
28 Osmotic Pressure pressure created by the solutes in a fluid. During osmosis, when water or any other solvent moves from the area of lower concentration to the area of higher concentration, the solutes in the area of higher concentration get dissolved in the solvent. This creates a pressure which is known as osmotic pressure. Normally, the osmotic pressure prevents further movement of water or other solvent during osmosis the osmotic pressure exerted by the colloidal substances (proteins) of the plasma is known as oncotic pressure (25 mm Hg)
29 Osmotic Pressure Normally, the osmotic pressure prevents further movement of water or other solvent during osmosis the osmotic pressure exerted by the colloidal substances (proteins) of the plasma is known as oncotic pressure (25 mm Hg)
30 Types of Osmosis Osmosis across the cell membrane is of two types: 1. Endosmosis: Movement of water into the cell 2. Exosmosis: Movement of water out of the cell.
31 Transport Across Cell Membrane - II
32 Active Transport vs Facilitated Diffusion 1.Carrier protein of active transport needs energy, whereas the carrier protein of facilitated diffusion does not need energy 2.In active transport, the substances are transported against the concentration or electrical gradient or both 3. In facilitated diffusion, the substances are transported along the concentration or electrical gradient or both Active transport Movement of molecules and ions against their concentration gradients (electrical or chemical or both) 1. Uses specific protein carriers 2. Requires energy (ATP)
33 Carrier Proteins of Active Transport 1.Uniport/ Uniport pump: Carrier protein that carries only one substance in a single direction 2. Symport/Antiport pump: The carrier protein carries two substances at a time Same direction: symport Opposite direction: antiport Two types: – Uniport – Symport or antiport
34 Mechanism of Active transport When a substance to be transported across the cell membrane comes near the cell, it combines with the carrier protein of the cell membrane and forms substance-protein complex. This complex moves towards the inner surface of the cell membrane. Now, the substance is released from the carrier proteins. The same carrier protein moves back to the outer surface of the cell membrane to transport another molecule of the substance.
35 Substance transported by Active transport Substances, which are transported actively, are in ionic form and non-ionic form. Substances in ionic form: Na +, K +, Ca ++, H+, Cl - and I - Substances in non-ionic form: glucose, amino acids & urea. Types of active transport Primary active Transport Primary active transport is the type of transport mechanism in which the energy is liberated directly from the breakdown of ATP
36 1. Primary Active Transport of Sodium and Potassium: Na + /K + Pump
37 thyroid hormones, insulin, aldosterone: Na/K pump increases Dopamine inhibits Na/K pump
38 Is present in sarcoplasmic reticulum of muscle cells Also located in cell membrane and in many cell organelle membrane In the cell membrane, the direction of Ca transport is from cytoplasm to ECF. cell organelle: from cytoplasm to organelle lumen 3. Potassium/Hydrogen pump or K + /H + ATPase Present in cells of gastric mucosa Secretes H + 2.Calcium pump or Ca ++ ATPase
39 Types of active transport Secondary Active transport Secondary active transport is the transport of a substance with sodium ion, by means of a common carrier protein Secondary active transport is of two types: 1. Co-transport 2. Counter transport
40 Types of Secondary active transport Now, the carrier protein is activated causing conformational changes in the carrier protein, so that Na + and glucose are released into the cell. Na + co-transport of glucose occurs during absorption of glucose from the intestine and reabsorption of glucose from the renal tubule Na + ions and glucose molecule from the ECF bind with the respective receptor sites of carrier protein of the cell membrane. Sodium co-transport of glucose
41 Types of Secondary active transport Sodium-hydrogen counter transport: In this system, the hydrogen ions are exchanged for sodium ions and this occurs in the renal tubular cells. The sodium ions move from tubular lumen into the tubular cells and the hydrogen ions move from tubular cell into the lumen Sodium Counter Transport
42 Composite diagram of main secondary effects of active transport of Na+ and K+. The energy of the gradients is used for countertransport, cotransport, and maintenance of the membrane potential Na+/K+ ATPase converts the chemical energy of ATP hydrolysis into maintenance of an inward gradient for Na+ and an outward gradient for K+.
43 Special Types of active transport (Vesicular Transport) 1. Endocytosis 2. Exocytosis 3. Transcytosis.
44 Special Types of active transport (Vesicular Transport) 1. Endocytosis larger molecules that cannot pass through the cell membrane either by active or by passive transport mechanism, are transported into the cell by endocytosis Endocytosis is of three types: 1. Pinocytosis 2. Phagocytosis 3. Receptor-mediated endocytosis.
45 Special Types of active transport (Vesicular Transport) 2. Exocytosis 3. Transcytosis
46 Molecular Motors Molecular motors are the protein-based molecular machines that perform intracellular movements in response to specific stimuli. FUNCTIONS OF MOLECULAR MOTORS 1. Transport of synaptic vesicles containing neurotransmitters from the nerve cell body to synaptic terminal 2. Role in cell division (mitosis and meiosis) by pulling the chromosomes 3. Transport of viruses and toxins to the interior of the cell for its own detriment.
47 Types Of Molecular Motors Molecular motors are classified into 3 super families: 1. Kinesin 2. Dynein 3. Myosin
48 References: Sebulingam, Essentials of Medical Physiology Ganong’s Review of Medical Physiology Guyton and Hall, Textbook of Medical Physiology