Biomembrane Structure 2024

Anchored Membrane Proteins by Covalently Linked Hydrocarbons (c) Exoplasmic face to GPI (glycolipids) – Glycosylphosphatidylinositol (a) Fatty acyl group attach to N term glyci...

Anchored Membrane Proteins by Covalently Linked Hydrocarbons (c) Exoplasmic face to GPI (glycolipids) – Glycosylphosphatidylinositol (a) Fatty acyl group attach to N term glycine. Anchors:(Myristate(C14) and palmitate (C16) are common acyl anchors (b) Hydrocarbon chain attach to cysteine residue at C terminus. Anchors: farnesyl(C15) and geranylgeranyl(C20)  Human ABO Blood Group Antigens Oligosaccharide chains covalently attached to glycolipids or glycoproteins in PM Terminal oligosaccharide sugars distinguish 3 antigens Presence or absence of glycosyltransferases that add galactose or GalNAc to O Antigen determines blood type Different blood types in US & Canadian populations Canada United States of America total Caucasian African American Hispanic Asian O+ 39% 37% 47% 53% 39% O- 7% 8% 4% 4% 1% A+ 36% 33% 24% 29% 27% A- 6% 7% 2% 2% 0.50% B+ 7.60% 9% 18% 9% 25% B- 1.40% 2% 1% 1% 0.40% AB+ 2.50% 3% 4% 2% 7% AB- 0.50% 1% 0.30% 0.20% 0.10% Information taken from the Canadian Blood Services and American Red Cross  Detergents Detergents are amphipathic molecules that disrupt membranes by intercalating into phospholipid bilayers and solubilize lipids and many membrane proteins proteins can be removed from membranes with detergents – Ionic detergents denature proteins – Non-ionic solubilize integral membrane proteins Yellow: Hydrophobic part attracted to hydrocarbons Blue: Hydrophilic part strongly attracted to H2O Sodium deoxycholate – bile salt is a natural product Principles of Membrane Biosynthesis New bio membranes are synthesized by expanding pre-existing membranes Many lipids are synthesized on the membranes of the smooth ER Final steps of membrane lipid synthesis takes place on destination membranes After synthesis, membrane lipids must be distributed to the appropriate leaflet & organellar membranes  Fatty Acid Synthesis Fatty acids can be synthesized from: – the enzymatic hydrolysis of triacylglycerol which is stored in adipocytes in mammals and other vertebrates, – or de novo from Acetyl CoA 14 and 16C fatty acids are synthesized in the cytosol by Acetyl-CoA carboxylase and fatty acid synthase. – Palmitoyl CoA (16C) can be elongated to 18-24C in the smooth ER membrane. All newly synthesized fatty acids are saturated. – Addition of double bonds occurs in the ER membrane by desaturase enzymes.  Intracellular Movement of Fatty Acids Fatty acids move within cells bound to cytosolic proteins called fatty acid binding proteins (FABPs). – Bind to hydrophobic pocket with which a long fatty acid chain can interact FABPs are up-regulated and down- regulated depending on the cellular requirements for the uptake and release of free fatty acids. A cell using fatty acids for respiration, FABP: ribbon diagram or an adipocyte releasing fatty acids, Fatty acid: yellow contains large numbers of FABPs 2 Oxygens: red within the cytosol.  Synthesis of Phospholipids Fatty acids converted into fatty acyl CoAs (CoA esters). 1. Fatty acyl CoA + glycerol phosphate are converted to phosphatidic acid by acyl transferases (esterases) on the smooth ER membrane. 2. Membrane phosphatase: converts phosphatidic acid to diacylglycerol 3. Choline phosphotransferase: transfers phosphocholine to diacylglycerol to form the phospholipid. 4. Flippase: transfers lipids from cytosolic leaflet to exoplasmic leaflet Cholesterol Synthesis Cytosolic acetyl CoA combines with acetoacetyl CoA forming HMG-CoA HMG-CoA converted to 6C mevalonate by HMG-CoA reductase HMG-CoA reductase embedded in SER membrane but has catalytic domain in cytosol Cytosolic enzymes convert mevalonate to IPP, Farnesyl pyrophosphate and squalene Squalene converted to cholesterol on SER membrane  Atherosclerosis Hardening of the arteries caused by blockage of arterial lumen Major cause of heart disease in the industrialized West Steps: – damage to endothelial cells – monocyte entry & conversion to macrophages – uptake of LDL – conversion to foam cells – foam cells accumulate – plaque formation Anti-atherosclerosis medications include statins – Bind to HMG-CoA reductase and directly inhibit its activity, so there is reduced cholesterol biosynthesis Transport of Lipids b/w Organelles Some cholesterol & phospholipids are transported via Golgi- dependent processes, especially if lipids bound to proteins 3 Golgi-independent mechanisms have been proposed for most lipid transport b/w organelles: (Figure 7-27) – via vesicles – direct contact b/w membranes mediated by integral proteins – mediated by soluble lipid-transfer proteins  q1 Which statements accurately describe membrane proteins? Select all that apply. A. All peripheral membrane proteins are predominantly hydrophobic. B. All integral membrane proteins are amphipathic. C. All transmembrane proteins are also integral membrane proteins. D. All transmembrane proteins contain a hydrophilic core that allows specific ions to pass through.  Q2 Which of the following components of biological membrane are amphipathic? Please select all that apply. a) Integral membrane proteins b) Phospholipids c) Glycolipids d) Membrane steroids such as cholesterol, sitosterol and ergosterol  Q3 Which of the following applies to membrane lipids? Please select all that apply. a) Membrane lipids are composed of hydrophobic molecules. b) Flippases are able to catalyze the transfer of lipid molecules between the outer and inner leaflets. c) Membrane lipids are able to spontaneously move between the outer and inner leaflets. d) Different lipid compositions are found in the two leaflets of a membrane.  Q4 In the plasma membrane, Glycolipids are usually situated in (a) cannot be predicted, it varies according to the cell types (b) inner leaflet of the plasma membrane (c) the outer leaflet of the plasma membrane (d) evenly distributed in both outer and inner leaves of plasma membrane