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Lysosomes

Lysosomes. Also Peroxisomes and Other Cellular Inclusions. Digestive System of the Cell. Digests ingested materials obsolete cell components Degrades macromolecules of all types Proteins, Nucleic acids, Carbohydrates, Lipids 50 different enzymes

jocelyn-cleveland
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Lysosomes

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  1. Lysosomes Also Peroxisomes and Other Cellular Inclusions

  2. Digestive System of the Cell • Digests • ingested materials • obsolete cell components • Degrades macromolecules of all types • Proteins, Nucleic acids, Carbohydrates, Lipids • 50 different enzymes • Interior is pH 5.0, proton pump helps it stay this way

  3. Products delivered to lysosomes by four routes: • Indiscriminate Pinocytosis • Cell “drinking” < 150nm • Receptor Mediated Endocytosis • Phagocytosis • Cell “eating” of material > 250nm • Autophagy • “self eat” of old worn out organelles, • important in cell degradation during apoptosis

  4. Lysosomal pathways Secondary lysosome phagosome phagocytosis phagocytosis Secondary lysosome pinocytosis pinocytotic vesicle pinocytosis Primary lysosome Receptor mediated endocytosis Coated pit RME autophagy Secondary lysosome Recycling of receptors to membrane Endosome Secondary lysosome Autophagic vacuole

  5. Primary lysosome • Buds from trans face of Golgi • exogenous materials, deteriorating organelles • Secondary lysosome • primary fuses with an endosome or phagosome • Usually look more electron dense

  6. Lysosomal enzyme deficiency

  7. Tay Sach’s Disease • A lysosomal storage disease • Due to a mutation in lysosomal enzymes B-N-hexosaminidase-A* • Accumulations of un-degraded glycolipid within lysosomes • Found in neurons of CNS Whorled inclusions (lamellar bodies) help I.D.Tay Sach’s

  8. Peroxisomes Crystalline inclusion • Similar structure to lysosomes • Single membrane • 200-300/cell • Abundant in kidney and liver • 0.2-1 mm • Consume oxygen • but not to form ATP as mitochondria Inclusion NOT found in humans, we don’t have urate oxidase

  9. Generates hydrogen peroxide detoxify various ingested molecules In kidney and liver Degrades hydrogen peroxide (H2O2) can be toxic to cells Using catalase to degrade hydrogen peroxide to water Synthesizes bile acids Metabolism of purines, alcohol Oxidation of fatty acids Provides energy Also done by mitochondria Peroxisome functions

  10. Cells with lysosomes • All cells have lysosomes, but a few cells are distinguished by abundance of lysosomes

  11. Macrophages • Includes histiocytes and Antigen Presenting Cells (APCs) • Histiocytes are fixed macrophages • Professional phagocyte, consuming debris and invaders in connective tissue • Originally from a monocyte

  12. Primary and secondary lysosomes of macrophage primary secondary Notice dark inclusions

  13. * Neutrophil • A professional phagocyte • First on the scene of an infection • Main component of pus

  14. Osteoclasts • Break down bone • Very large cells from monocyte and macrophage fusion • Stain pink in H&E due to presence of acid contents of lysosomes

  15. Cellular inclusions • Unlike organelles, they do not have specified functions • Exogenous • Usually harmful, heavy metals, etc. • Endogenous • Metabolic • Lipid, glycogen, mucigen • Pigments • Lipofuscin, melanin • Crystalloids • Unknown function

  16. Endogenous inclusions • Lipid droplets • Found in adipose, hepatic cells, some steroid secreting cells • Clear in standard LM preps, dark in standard TEM preps • Important nutritional reserves FH 4.13

  17. Note sER Glycogen • Principle storage form of carbohydrates • Liver, muscle, adrenal cortex • Requires special stain to be seen with LM • In TEM, can see rosette clumps of electron dense material • Too much glycogen results in Pompe’s disease: liver enlargement, lysosomal deficiency

  18. Enzyme precursors • Zymogen • Found in apical portion of the cell • Contain precursors of many enzymatic proteins • Pancreas • trypsinogen • Chief cells of stomach • pepsinogen • Salivary glands • Precursor to amylase

  19. Enzyme precursors, continued • Mucigen • Secreted by goblet cells • Found in respiratory and gastrointestinal tract epithelial linings • When mucigen released by exocytosis, mixes with water to form mucus • Used for protection • Local irritation can cause cell to release entire contents

  20. Pigments • Lipofuscin • Unknown function, but increases with age, especially in neurons • Yellow brown, fluorescent • Represents accumulation of insoluble intracellular debris after lysosomal activities • Melanin • Imparts color to skin and hair • Neuromelanin also found in some multipolar neurons

  21. Crystalloids • Eosinophils • white granulocyte • Specific granules have lamellated, angular, crystalloid cores • “Cat-eye” shape

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