MED1003 Week 5 Seminar PDF

The endomembrane system and peroxisomes II by Siu Wai (Phyllis) TSANG, PhD TUNG WAH COLLEGE email: [email protected] Office#: 3190-6713 Prepared by SWT 2024 email: [email protected] 1  https://open....

The endomembrane system and peroxisomes II by Siu Wai (Phyllis) TSANG, PhD TUNG WAH COLLEGE email: [email protected] Office#: 3190-6713 Prepared by SWT 2024 email: [email protected] 1  https://open.oregonstate.education/app/uploads/sites/178/2023/11/FIgure-04-01.png Prepared by SWT 2024 email: [email protected] trafficking 2 Endomembrane trafficking Each protein contains a specific “tag” targeting the protein to a transport vesicle that will carry material from one specific cellular location to another Depending on the protein and its destination, the tag may be a short amino acid sequence, an oligosaccharide side chain, a hydrophobic domain, or some other structural feature Tags may also be involved in excluding material from certain vesicles Membrane lipids may also be tagged to help vesicles reach their proper destinations This tag can be one or more phosphate groups attached to the molecules Apart from tags on lipids, the length and degree of saturation of certain membrane lipids also help in vesicle trafficking Prepared by SWT 2024 email: [email protected] 3  Trafficking (cont’d) The modified proteins are sorted (based on markers such as amino acid sequences and chemical tags) and packaged into vesicles that bud from the trans face of the Golgi Some of these vesicles deliver their contents to other parts of the cell where they will be used, e.g., other organelles images/0effee87f40002dfe966cb61199940e69409f394.png Others fuse with the plasma membrane, secreting out of the cell https://cdn.kastatic.org/ka-perseus- In mammalian cells, inhibition of inositol kinases disrupts vesicle trafficking to the lysosome 4 Prepared by SWT 2024 email: [email protected] Endomembrane trafficking (cont’d) Cells that secrete many proteins—such as salivary gland cells that secrete digestive enzymes, or cells of the immune system that secrete antibodies— have many Golgi stacks In plant cells, the Golgi apparatus has the additional role of synthesizing polysaccharides, some of which are incorporated into the cell wall and some of which are used in other parts of the cell Some proteins retain in the ER contain the tripeptide sequence RXR (Arg-X- Arg, where X is any amino acid), which appears to promote retention in ER Some resident proteins of the Golgi apparatus also contain retention tags Prepared by SWT 2024 email: [email protected] 5 Protein targeting Proteins that move out of the Golgi apparatus must be targeted to end up in the right place e.g., endosomes, lysosomes, secretory vesicles, etc… Soluble lysosomal proteins are targeted by recognition of mannose-6- phosphate in the carbohydrate side chains by specific receptors on the membrane of trans-Golgi compartment pH in trans-Golgi is ~6.4 favoring binding of soluble lysosomal enzymes to these receptors These receptor/protein complexes are then packaged into clathrin-coated transport vesicles, and conveyed to an endosome Prepared by SWT 2024 email: [email protected] 6 Lysosomal enzymes carry distinctive mannose-6- phosphate tags that direct them to lysosomes Prepared by SWT 2024 email: [email protected] 7 The endomembrane system – Endosomes & lysosomes Prepared by SWT 2024 email: [email protected] 8 Endosomes Endosomes are membrane-bound vesicles formed upon endocytosis Endosomes are typically involved in sorting and delivery of protein and lipid vesicles and their contents to and from the plasma membrane At endosomes, the internalized contents are either recycled back to the plasma membrane or are sorted for degradation The ‘early’ endosomes are positioned close to sites of active endocytosis, they provide a sorting environment for lipid, protein, and extracellular molecules contained within endocytic vesicles The “late” endosomes fuse directly and completely with lysosomes to form a hybrid organelle Prepared by SWT 2024 email: [email protected] 9 Endosomes (cont’d) Textbook Ch.12 p.365 Prepared by SWT 2024 email: [email protected] 10 Lysosomes The lysosome is a membrane-bound organelle of the endomembrane system that contains digestive enzymes capable of degrading all the major classes of biological macromolecules—lipids, carbohydrates, nucleic acids and proteins These hydrolytic enzymes (>60 types of hydrolases) degrade extracellular materials brought into the cell by endocytosis and digest intracellular structures and macromolecules that are damaged or no longer needed Lysosomal enzymes are synthesized by ribosomes attached to the rough ER Lysosomes fuse with endosomes, aiding the digestion of materials inside the endosome Prepared by SWT 2024 email: [email protected] 11 Lysosomes (cont’d) Why don’t lysosomes digest themselves? Most of the proteins found in the membrane of a lysosome have an unusually large number of carbohydrates attached to them These carbohydrate groups making up the glycocalyx protective layer protect the membrane proteins by preventing the digestive enzymes in the interior of the lysosome from breaking them down Prepared by SWT 2024 email: [email protected] 12 Lysosomes (cont’d) Whereas most digestive processes involving lysosomal enzymes occur intracellularly, in some cases lysosomes discharge their enzymes to the outside of the cell by exocytosis, resulting in extracellular digestion e.g., The head of the sperm releases lysosomal enzymes capable of degrading barriers that would otherwise prevent contact between the sperm and egg membranes Certain inflammatory diseases, such as rheumatoid arthritis, may result from the inadvertent release of lysosomal enzymes by white blood cells in the joints, damaging the joint tissue Prepared by SWT 2024 email: [email protected] 13 Peroxisomes Prepared by SWT 2024 email: [email protected] 14 Peroxisomes Peroxisomes are specialized for carrying out oxidative reactions using molecular oxygen Peroxisome is known to be an organelle that sedimented at a slightly different density in a sucrose density gradient than lysosomes https://o.quizlet.com/CnNkL8wPgCKaQy3r-YiKHA.png Prepared by SWT 2024 email: [email protected] 15 Peroxisomes (cont’d) Similar to Golgi apparatus, endosomes and lysosomes, peroxisomes are bounded by single membranes Peroxisomes are NOT derived from the ER and are NOT part of the endomembrane system They are found in all eukaryotic cells but are especially prominent in mammalian kidney and liver cells, in algae and photosynthetic cells of plants and in germinating seedlings of plant species Peroxisomes are somewhat smaller than mitochondria, though there is considerable variation in size, depending on their function and the tissue where they are found Prepared by SWT 2024 email: [email protected] 16 Peroxisomes (cont’d) Hydrogen peroxide (H2O2) metabolism H2O2 is a potentially toxic compound formed by oxidases The peroxisome contains catalase, an enzyme essential for the degradation of hydrogen peroxide  detoxification of H2O2 Both catalases and oxidases are confined to peroxisomes The generation and degradation of H2O2 occur within the same organelle, thereby protecting other parts of the cell from exposure to this harmful compound Detoxify reactive oxygen species such as, superoxide anion and hydroxyl radical, as well as other toxic substances, e.g., methanol, ethanol, formic acid, formaldehyde, nitrites and phenols  reduce oxidative damage to cellular components Prepared by SWT 2024 email: [email protected] 17 Peroxisomes (cont’d) Oxidation of fatty acids About 25–50% of fatty acid oxidation in animal tissues occurs in peroxisomes (with the remainder localized in mitochondria)  provides energy for the cell In animal cells, peroxisomal β oxidation is especially important for degrading long- chain (16–22 carbons), very long chain (24–26 carbons), and branched fatty acids The primary product of β oxidation, acetyl-CoA, is then exported to the cytosol, where it enters biosynthetic pathways or the citric acid cycle In plants and yeasts, peroxisomes are essential for the complete catabolism of all fatty acids to acetyl-CoA Prepared by SWT 2024 email: [email protected] 18 ~ The end ~ Prepared by SWT 2024 email: [email protected] 19