Transfusion Red Cell Membrane PDF
Document Details
Uploaded by LikedJoy
Geoff White
Tags
Summary
This document provides an overview of the red cell membrane, its components, and functions. It details the structure, composition, and roles of proteins and lipids in cellular transport and maintenance of the red blood cell structure. This session aims to give an understanding of the Red Cell Membrane and its components and explain how structures in the red blood cells work together to maintain and maximize the lifespan of these blood cells.
Full Transcript
Geoff White (from Moore, Knight & Blann,2010) 1 Session Aims and Outcomes this session aims for you to gain an understanding of : the Red Cell Membrane and its Constituents function of the Red Cell Membrane How structure of red cell membrane allows...
Geoff White (from Moore, Knight & Blann,2010) 1 Session Aims and Outcomes this session aims for you to gain an understanding of : the Red Cell Membrane and its Constituents function of the Red Cell Membrane How structure of red cell membrane allows it to perform its function By the end of this session you should be able to explain: How the red blood cells membrane and constituents work together How the membrane works to maximise red cell lifespan How the structure of the membrane relates to its function. Red Blood Cells ‘erythrocytes’ have a bi-concave disc shape their role is to transport respiratory gases to/from tissues deliver oxygen (O2) to the tissues where active metabolism is going on to remove the waste products of metabolism from the tissues Red Cell Facts on average a healthy adult male has 5,000,000,000,000 in each litre of blood they develop in the bone marrow but lose their nucleus by the time they reach the bloodstream contain Haemoglobin which enables oxygen delivery to the tissues average life-span of 120 days in the blood circulation reduced life-span can lead to haemolytic anaemia Function of Red Cell Membrane function in microcirculation means red cell membrane must be tough but flexible and show deformability achieved by interaction of a protein cytoskeleton with the membrane lipid bilayer main functions separate the cell contents from the plasma maintain characteristic shape regulate intracellular cat ion concentrations site of membrane surface receptors The Red Cell Membrane composed of an outer Glycocalyx carbohydrate ‘coat’ made up of both extracellular proteins and glycosylated proteins & lipids from the Lipid Bilayer underneath is the framework of peripheral proteins that comprise the red cell Cytoskeleton Chemical structure 44% lipid acts as permeability barrier comprise a basic phospholipid bilayer 49% protein integral or peripheral provide skeletal structure and selective transport across membrane 7% carbohydrate associated with proteins/polypeptides or lipid (ie glycosylated) presented on the outside of the membrane The Red Cell Membrane Red Cell Membrane showing Glycocalyx, Lipid Bilayer & Cytoskeleton (from Issitt & Anstee,1999) Composition of the Red Cell Membrane Membrane Lipids 30% cholesterol 60% Phospholipid Phosphatidyl choline (lecithin) Sphingomyelin Phosphatidyl ethanolamine Phosphatidyl serine characterised by polar head group attached to a non- polar fatty tail arranged in a bilayer fluidity allows movement of ‘rafts’ 10% glycerides/FFA Composition of the Red Cell Membrane Integral Proteins Band 3 facilitates anion transport across the membrane binding site for skeletal and other red cell proteins has binding sites for Hb, ankyrin, Band 4.1, Band 4.2 Glycophorins (A,B,C,D,E) Sialoglycoproteins provide negative charge act as binding sites for viruses, bacteria, parasites required for structural integrity of the red cell Glucose Transport Protein 12 trans-membrane domains surface concentration varies Rh Proteins associated into a macrocomplex transport function & interacts with cytoskeleton Peripheral Proteins of the Cytoskeleton membrane peripheral proteins interact to form the cytoskeleton Peripheral Proteins are Spectrin subunits bind in an anti-parallel arrangement associates with Ankyrin, band 4.1, actin & anionic phospholipids Ankyrin found in 2 forms anchors spectrin molecules to the lipid bilayer Actin globular protein that polymerises readily to form filaments bind weakly to the tail end of spectrin and holds together in a 2D lattice Band 4.1 globular protein that binds to spectrin close to the actin binding site binds directly to glycophorins A & C, Band 3, phosphatidyl serine & ankyrin Peripheral Proteins of the Cytoskeleton membrane peripheral proteins interact to form the cytoskeleton Peripheral Proteins are Spectrin subunits bind in an anti-parallel arrangement associates with Ankyrin, band 4.1, actin & anionic phospholipids Ankyrin found in 2 forms anchors spectrin molecules to the lipid bilayer Actin globular protein that polymerises readily to form filaments bind weakly to the tail end of spectrin and holds together in a 2D lattice Band 4.1 globular protein that binds to spectrin close to the actin binding site binds directly to glycophorins A & C, Band 3, phosphatidyl serine & ankyrin Peripheral Proteins of the Cytoskeleton membrane peripheral proteins interact to form the cytoskeleton Peripheral Proteins are Spectrin subunits bind in an anti-parallel arrangement associates with Ankyrin, band 4.1, actin & anionic phospholipids Ankyrin found in 2 forms anchors spectrin molecules to the lipid bilayer Actin globular protein that polymerises readily to form filaments bind weakly to the tail end of spectrin and holds together in a 2D lattice Band 4.1 globular protein that binds to spectrin close to the actin binding site binds directly to glycophorins A & C, Band 3, phosphatidyl serine & ankyrin Integral Proteins Glucose Transport Protein (GLUT 1) Glycophorin A Red Cell Na+/K+ ATPase ‘ cation pump’ enzyme composed of 3 protein subunits catalyses the conversion of ATP to ADP to release energy ADP formed is reconverted to ATP by the EM Pathway each ATP hydrolysed removes 3 Na+ molecules and subsequently transports 2 K+ into the cell Mechanism of Na+/K+ ATPase ‘pump’ Phosphorylation (energy release) of the pump transports out 3 NA+ molecules Dephosphorylation transports 2K+ into the cell Peripheral Proteins of the Cytoskeleton membrane peripheral proteins interact to form the cytoskeleton Peripheral Proteins are Spectrin subunits bind in an anti-parallel arrangement associates with Ankyrin, band 4.1, actin & anionic phospholipids Ankyrin found in 2 forms anchors spectrin molecules to the lipid bilayer Actin globular protein that polymerises readily to form filaments bind weakly to the tail end of spectrin and holds together in a 2D lattice Band 4.1 globular protein that binds to spectrin close to the actin binding site binds directly to glycophorins A & C, Band 3, phosphatidyl serine & ankyrin Representation of Membrane Structure Primary Membrane Disorders inherited disorders of the red cell membrane affects cell shape reduced life-span can lead to compensated anaemia Hereditary Spherocytosis autosomal inheritance results in defective/deficiency of skeletal proteins mainly affects spectrin causes spherocytosis & haemolytic anaemia Primary Membrane Disorders Hereditary Elliptocytosis presence of a large proportion of oval or elliptical cells defective spectrin, Band 4.1, or Band 3 Rh Null Syndrome absence of Rh Polypeptides and RhAG in membrane stomatocytosis & spherocytosis observed in peripheral blood patient experiences compensated haemolytic anaemia