Cell Structure & Transport I_202409016 Lecture Notes PDF

Cell structure & Transport 12 Sep 2024 Simon Fung ! Cell vs System ! ! Organelle vs Organ ! Schematic Overview of Eukaryocyte Highlights 1. Refresh what they might have learnt about CELL BIOLOGY (structure & function) in BIO2036 or other course 2. Arouse their interest to fa...

Cell structure & Transport 12 Sep 2024 Simon Fung ! Cell vs System ! ! Organelle vs Organ ! Schematic Overview of Eukaryocyte Highlights 1. Refresh what they might have learnt about CELL BIOLOGY (structure & function) in BIO2036 or other course 2. Arouse their interest to familiarize themselves with the importance of most cellular functions e.g. cell/mitochondria membrane transport 3. How this function relate to our health status and health maintenance 4. Relationship with the dyfunction of these organelles to the relevant disease caused e.g. Cell transport protein – Cystic Fibrosis, Carnitine deficiency Cytoskeleton - cardiovascular disease syndromes (?HCM/DCM), eurodegeneration (?SCA) or blistering skin diseases More in details… Cell transport protein in Plasma membrane – bilipid (phospholipid) layer, protein, cholesterol Mitochondria membrane Protein trafficking e.g. endocytosis/exocytosis Cytoskeleton – actin filament, intermediate filament, microtubule About the diseases Cell structure Foci on cellular components: Cell transport (plasma membrane) Cytoskeleton Others: Endocytosis & Exocytosis Lyzosome Peroxisome etc. Cell (plasma membrane) e.g. hCG, hormones receptors e.g. Red cell antigen The Fluidity of a Lipid Bilayer Depends on Its Composition e.g.Cholesterol Four major phospholipids in mammalian plasma membrane What are Conjugated Molecules in Biology? Glycoprotein, Glycolipid, Lipoproteins and Nucleoproteins (ahmadcoaching.com) https://www.ahmadcoaching.com/2022/01/what-are-conjugated-molecules-in-biology.html General concepts on cell transport: Both the Concentration Gradient and Membrane Potential Influence the Passive Transport of Charged Solutes Facilitated diffusion Active transport Each cell membrane has its own characteristic set of transporters With direction ! Need energy ! A glucose–Na+ symport uses the electrochemical Na+ gradient to drive the active import of glucose Roles of protein in membrane Cell membrane contain specialized membrane transport proteins - Facilitate the passage of selected small, water soluble molecules  Examples The Ca2+ pump in the sarcoplasmic reticulum was the first ATP-driven ion pump to have its 3-dimensional structure determined by x-ray crystallography. The Na+ pump uses the energy of ATP hydrolysis to pump Na+ out of animal cells and K+ Animal and plant cells use a variety of transmembrane pumps to drive the active transport of solutes Mitochondria - Role importance Mitochondria vs Chloroplasts  Mitochondria’s double membrane Raw materials for energy production 1. Outer membrane  Substances in and out e.g. nutrient & ATP 2. Inner membrane  Oxidative phosphorylation in respiratory (e-transport) chains: NADH to NAD+ > generate ATP e.g. fatty acid oxidation  Protein transport in and out between cytosol & inner membrane e.g. carnitine Example of respiratory chain enzymes The transport protein (Carnitine) shuffles between cytosol and inner mitochrondria membrane in Fatty Oxidation (energy yielding)  Protein trafficking - is the transport of proteins to their correct subcellular compartments or to the extracellular space (“secretory pathway”). Cell Transport - Endocytosis, Exocytosis, Phagocytosis, and Pinocytosis https://www.youtube.com/watch?v=jn4MTkqbZjg Protein Trafficking, I-Cell Disease, Clathrin, Vesicular Transport & Protein Modifications https://www.youtube.com/watch?v=4sWnK7OqK-k&t=33s Protein trafficking - Protein ship to specific locations within cell Usual involvements: Exocytosis Rough endoplasmic reticulum- mainly protein synthesis Golgi apparatus – mainly post- translational modification e.g branch chain added (glycosylation) Transport/secretory vesicle  Endocytosis (opposite direction) e.g. Pinocytosis, Phagocytosis Aided by pseudopdium, receptor- mediated Membranes retain their orientation during transfer between cell compartments Phagocytosis - where endocytosis & exocytosis can both occur Synatic endocytosis & exocytosis - within pre-synape or post-synape Reminder Cell transport protein in Plasma membrane – bilipid (phospholipid) layer, protein, cholesterol Mitochondria membrane Protein trafficking e.g. endocytosis/exocytosis  Diseases Cell membrane protein Transport protein Cystic Fibrosis - membrane protein defect  Cystic Fibrosis: Pathophysiology, Genetics, Symptoms, Diagnosis and Treatments https://www.youtube.com/watch?v=Ihx19-56Kzc Cystic Fibrosis transmembrane conductance regulator (CFTR) CFTR (Chloride ion transporter) Introduction - Incidence, Genetics, Sign & complication etc. 1 child in 2000 born most common lethal hereditary disease of Caucasians. 1 African in 15,000; 1 Asian in 32,000. 1 in 25 is an unaffected carrier in US. In all, there are about 10 million carriers. Nowadays a child may live to as long as 30-40 years of age. CF gene occurs on chromosome 7 & chromosome 1 encodes for a protein called the CF antigen forming the transport protein - cystic fibrosis transmembrane conductance regulator (CFTR) which regulates the passage of chloride and sodium ions across epithelial membranes.  An autosomal recessive disorder, more than 1000 known gene mutations. Predominant deletion mutation of phenylalanine 508 is part of the nucleotide- binding function in ATP-binding domain (NBD1, NB2). Mutant CFTR (CFTR δ-F508) protein is synthesized but fails to be modified in the endoplasmic reticulum (ER) and becomes degraded. CFTR is the only anion channel in sweat gland duct (chloride ion transporter) & regulation of the bicarbonate ion (HCO3 ) in the pancreatic duct. They are poorly functional or nonfunctional in CF patient. CFTR is synthesized in epithelia of the pancreas and lung, colon, sweat gland, kidney proximal tubules etc. Cystic Fibrosis - membrane protein defect CFTR = chloride ion transporter  Pathogenesis/Pathophysiology/Pathology - Cellular & functional defect In the presence of ATP, the channel is open. Cl ions to flow in in or out of the cell of the electrochemical gradient. CFTR inhibits the function of ENaC so that there would be an excess of NaCl on the outside of the cell driving Cl movement through the CFTR from the intracellular space to the extracellular space. In the absence of ATP, the channel is closed and Cl does not flow in either direction. In the sweat gland the reabsorption of salt is abnormal in cystic fibrosis. CFTR is the only anion channel in the duct of the sweat gland and it is nonfunctional in cystic fibrosis. Chloride transfer would be absent and because the transport of chloride is followed by water, causing the reduction of water transport. Sweat becomes concentrated in sodium chloride (>60 mmol/L in sweat is diagnostic); thus the salty sweat condition of the person with this disease and the deficient secretion of digestive enzymes from the pancreas lead to the development of thick mucus. This defect occurs in many tissues and causes great difficulty in the lung where breathing problems and infections develop. In the newborn, stools do not develop within the first 24 to 48 hours of life meconium ileus 胎便 occurs or obstructive mass (meconium) in the intestine due to the low secretions of digestive enzymes from the pancreas. Sign & complication Defective Cl & water export out of cell> dry secretion High sweat Cl in CF patient Thick mucus in lung> recurrent lung disease and infection Pancreatic enzyme secretion e.g. trypsinogen > high blood trypsinogen level Diagnosis Newborn screening  Immunoreactive trypsinogen Sweat chloride test,  chloride (>60 mmol/L in sweat is diagnostic) Genetic testing for CFTR mutation https://www.testing.com/tests/immunoreactive-trypsinogen-irt/ Cystic Fibrosis - Diagnosis | NHLBI, NIH Cystic fibrosis - Diagnosis and treatment - Mayo Clinic Treatment  What Is Cystic Fibrosis? With primary treatments https://www.youtube.com/watch?v=k4U5wyPzxJE  Cystic Fibrosis Mechanism and Treatment https://www.youtube.com/watch?v=6IbP1ASGv9w e.g. Pancreatic digestive enzyme supplements clear buildup of mucus and mucus-clearing drugs and antibiotics A lung transplant in lungs failure Others links Cystic Fibrosis https://www.youtube.com/watch?v=4IGz5p4n8Fg https://www.youtube.com/watch?v=6IbP1ASGv9w https://www.youtube.com/shorts/Cdgu9MwRJ84 Carnitine Deficiency (Supp.) - transport protein deficiency in mitochondria 1. Introduction & background knowledge Primary carnitine deficiency https://www.youtube.com/results?search_query=carnitine+deficiency 2. Foci on: Introduction e.g. prevalence, clinical manifestation, sign & symptom, complication etc Etiology (various underlying causes for disease) Pathophysiology/Pathology/Pathogenesis Diagnosis (DX or DDX) Treatment (Tx) Carnitine Deficiency - StatPearls - NCBI Bookshelf (nih.gov) Systemic Primary Carnitine Deficiency - GeneReviews® - NCBI Bookshelf (nih.gov) Primary and secondary carnitine deficiency syndromes - PubMed (nih.gov) Refer to the main book for details Alberts, B., Hopkin, K., Johnson, A., Morgan, D., Raff, M., Roberts, K., & Walter, P. (2023). Essential Cell Biology (6th ed.). W. W. Norton & Company. Chapters on:  11- CELL MB STRUCTURE,  12- TRANSPORT ACROSS CELL MB  PRINCIPLES OF TRANSMEMBRANE TRANSPORT  TRANSPORTERS AND THEIR FUNCTIONS  15- INTRACELLULAR COMPARTMENT & PROTEIN TRANSPORT  membrane-enclosed organelles  vesicular transport  secretory pathways o endocytic pathways  17- CYTOSKELETON