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Phospholipids
Uni of Notts, Signalling & Metabolic Regulation, year 2, topic 16
| Term | Definition |
|---|---|
| General structure of phospholipids | Sn1 (C1) saturated fatty acid, sn2 unsaturated, sn3 phosphate, alcohol head group esterified to phosphate |
| Why sn1 is usually saturated & sn2 is usually unsaturated | Evolutionary selection of enzymes with G3P acyltransferase favouring saturated & 1-acyl-CoA & 1-acyl G3P acyltransferase favouring unsaturated. This balance maintains ideal membrane fluidity |
| Lipid flip-flop | Diffusion of phospholipids between membranes, slow without flipase enzymes due to amphipathic nature |
| Phosphatidylcholine (PC) | -OCH2CH2N+(CH3)3. Zwitterionic cylindrical. Most abundant phospholipid in mammalian cells & makes up most of outer leaflet. Synthesised from methylated PE (PEMT) or Kennedy pathway. Precursor to DAG for DAG signalling |
| Phosphatidic acid (PA) | -H. Negative, very conical. Promotes membrane curvature for budding & recruitment of basic proteins. Signalling molecule. An intermediate in fat synthesis |
| Phosphatidylethanolamine (PE) | -OCH2CH2NH2. Zwitterionic conical. Promotes negative membrane curvature for fusion, autophagy, & fission. Common in inner leaflet and stabilises membrane proteins. Used in PMT |
| Phosphatodylserine (PS) | -OCH2CH(NH2)COOH. Negative conical. Negatively charges inner leaflet recruits signalling proteins like PK-C. When flipped to outer leaflet, can anchor signalling factors for apoptosis |
| Phosphatidylinositol (PI) | -OCH(CH(OH))5. Negative bulky head. Rarest, used in important signalling pathways & is precursor to PIP2 & PIP3. Contains stearic acid to anchor & arachidonic acid to be converted into different signalling molecules |
| Diphosphatidylglycerol (cardiolipin) | Glycerol linking 2 phosphatidates. Very negative very conical. Exclusively in inner mitochondrial membrane. Stabilises respiration chain complexes, needed for oxidative phosphorylation & curve cristae |
| Kennedy pathway | Activation of phosphorylated DAG or choline/ethanolamine group by adding a CMP to form R-CDP so head group transfer is thermodynamically feasible. PE can also come from decarboxylated PS |
| PC rate-determining step regulation | Rate determining step is converting phosphocholine to choline-CDP using cytidylyltransferase (CCT), but only active if membrane bound, PC packs the membrane more tightly which prevents CCT binding |
| General biosynthesis pathway | G3P obtained either by phosphorylating glycerol, reducing DHAP, or partially lysing a TAG to PA. Parts must be activated by NTP then CTT |
| Sphingolipid | Glycerol backbone is replaced by L-shaped sphingosine, only 1 fatty acid can bind using an amide bond (ceramaide). Structure is more liquid so can be used to form lipid rafts & caveolae |
| Lipid rafts & caveolae | Lipid raft: Dynamic transient membrane microdomains Caveolae: Small membrane invaginations involved in trafficking & signalling |
| Phosphosphingolipid formation + example | Sphingosine is an amino alcohol & the alcohol group can be phosphorylated & activated with CTP & choline or ethanolamine. If ethanolamine is added, it makes sphingomyelin (myelin sheath) |
| How membranes are self-healing | Exposing water molecules to hydrophobic fatty acid core causes very ordered molecules reducing entropy. This is thermodynamically not favourable & hydrophobic attraction repairs the hole |
| How lipid imbalance can lead to disease | Membrane fluidity, curvature, signalling, vesicle trafficking, apoptosis, mitochondria function & protein localisation are altered leading to cancer, cardiomyopathy, neurodegeneration, liver disease, & autoimmune dysfunctions |
Created by:
Denny12
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