FINAL NOTES.pdf

Module 18: Lysosomal Enzymes and Cell Diseases I-Cell Disease: - Involves undigested glycosaminoglycans. Tay-Sachs Disease: - Accumulation of GM2 due to deficiency of Hexosaminidase A. - Leads to psychomotor retardation. Lysosomal Enzymes: - When they escape the cytoplasm, they are captured by M...

Module 18: Lysosomal Enzymes and Cell Diseases I-Cell Disease: - Involves undigested glycosaminoglycans. Tay-Sachs Disease: - Accumulation of GM2 due to deficiency of Hexosaminidase A. - Leads to psychomotor retardation. Lysosomal Enzymes: - When they escape the cytoplasm, they are captured by MPRs. Characteristics of Lysosomal Proteins: - Synthesized on ER ribosomes and secreted into the cytoplasm. Module 19: Autophagy and Cell Cycle Regulation Microautophagy: - Lysosomes engulf cytoplasm. Macroautophagy: - Vesicles, chaperones form autophagosome. Cell Cycle Regulation: - Short-lived proteins are marked for degradation by ubiquitination. - Long-lived proteins are degraded by lysosomes. Proteasome Pathway: - Before entering a proteasome, ubiquitinated proteins are deubiquitinated and unfolded. Module 20: Extracellular Matrix and Glycosaminoglycans Glucosamine in Osteoarthritis Therapy: - Increases GAGs (glycosaminoglycans) which are important proteoglycans in cartilage. Glycosaminoglycans (GAGs) in ECM: - Form gels that retain water (H₂O). Basal Lamina: - Acts as a barrier for macromolecules. Proteins in the ECM: - Perlecan: Proteoglycan. - Entactin/Nidogen: Glycoproteins. Diseases Related to ECM: - Duchenne Muscular Dystrophy: Mutations in the dystrophin gene. - Congenital Muscular Dystrophy: Mutations in laminin α2. Role of the Basal Lamina in Kidneys: - Involved in filtering macromolecules in the glomerulus. Module 21: Proteoglycans, Fibers, and Collagen Proteoglycan: - Provides structural support. Fibronectin: - Associates with collagen and aggregates to form fibers. Hydroxylation: - Involved in collagen synthesis to initiate collagen fibril aggregation. Fibronectin (Adhesive Protein): - Not fibrous, but organizes the ECM. Fibrous Proteins: - Elastin, Collagen, Fibrin form structural elements. Collagen Types: - Type I: Provides tensile strength. - Type II: Fibril interaction. Amino Acids in Collagen: - Proline and Glycine are abundant in collagen. Propeptide: - Involved during collagen synthesis. ECM Degradation on Cancer Cells: - Assists in cell migration. Globular Proteins: - Exhibit compact structure. Laminin: - Aids in epithelial tissue adhesion. Primary Function of Adhesive Proteins: - Fibronectin and Laminin help organize the ECM. Module 20, 21, 22: Laminin and Collagen Laminin & Basement Membrane Assembly: - Self-polymerizes in the extracellular space to form a sheet-like structure. - Interacts with integrins and dystroglycans (anchors). Collagen Polymers: - Join laminin in the sheet, stabilized by glycoprotein nidogen and proteoglycan perlecan. Osteoarthritis: - Cartilage wear on bones, treated with chondroitin and glucosamine supplements. Main Structural Protein: - Collagen fibrils, modified in the rough ER. Peroxisomes, Microtubules, and Actin: - Involved in cellular transport mechanisms. Fibronectin Isoforms: - Produced by alternative splicing of one large gene (with 50 exons). Basal Lamina: - Underlies all epithelia as a supportive sheet. Quiz: Collagen and ECM-Related Diseases Collagen Type IV: - Major part of the basement membrane. Glycine and Proline: - Key amino acids in collagen formation. Scurvy: - Defects in collagen synthesis due to lack of hydroxyproline (vitamin C deficiency). Collagen Types and Functions: - Type IV Collagen: Muscular dystrophy. - Type IX/XII Collagen: Fibril interaction. - Type VII Collagen: Epidermis adhesion. Substitution of Nucleotide: - Affects collagen types I, III, and IV. Proteoglycans: - Trap water molecules, form hydrated gel, and draw water by osmosis. Negative Charges in ECM: - Trap cations to maintain neutrality. Water equalizes concentrations inside and outside the cell. Point Mutations: - More dangerous than deletions. Protein Structure: - Amino terminal (left) and carbonyl terminal (right). Set #6: Protein Degradation Pathways and the Unfolded Protein Response (UPR) UPR (Unfolded Protein Response): - Signals sent to the nucleus to slow down gene expression. Autophagy: - Cell death; the cell's ability to degrade and recycle its own non-essential organelles. Classes of Proteins: 1. Lysosomal proteins. 2. Secretory molecules. 3. Plasma membrane-resident proteins (sometimes cycle within endosomal compartments). Proteasome: - Proteolytic complex with ATPase, degrades proteins. V-ATPase: - Pumps protons into the lysosome to maintain low pH. Low pH: - Increases proton concentration inside lysosomes. Late Endosomes: - Converted to mature lysosomes by loss of specific proteins and lower pH. Retrograde Transport: - Following cargo unloading, MPR receptors are recycled back to the trans-Golgi. Lysosomal Enzymes and MP6 Tags 1. MP6 Tags: Enzymes escape the MP6 sorting pathway to lysosomes. 2. Secretion of Lysosomes: Some lysosomes are secreted. 3. Functionality of MP6: Enzymes remain functional with an MP6 tag. 4. MP6 Receptors on Plasma Membrane: Receptors bind escaped enzymes via receptor- mediated endocytosis. 5. Endocytosis and Enzyme Delivery: Enzymes are taken into cells via clathrin-coated pits, delivered to endosomes. 6. Extracellular Proteins: Normally do not cross the membrane into the cytosol. 7. Foreign Proteins: Delivered to lysosomes/proteasomes for degradation.