BIOCELL GEN Lecture 8 endomembrane system II

• The Endomembrane System


  • Structure
  • Functions

  
• Components of the Endomembrane System

  • Plasma membrane
  • Nuclear envelope
  • Endoplasmic Reticulum
  • Golgi Apparatus
  • Lysosomes
  • Vacuoles

  
• Endomembrane System


  • Related either by physical contact or by transfer of vesicles (sacs made of membrane)

  
• Functions of the Endomembrane System


  • Storage & trafficking
  • Metabolism
  • Detoxification

  
• Protein Trafficking within the Endomembrane System

  1. Sorting signals direct the movement

  2. Gated transport

  3. Transmembrane transport

  4. Vesicular transport
• Lysosomes


  Membranous sac of hydrolytic enzymes that can digest macromolecules

  
• Lysosomes


  • Lysosomal enzymes work best in the acidic environment inside the lysosome
  • Lysosomal enzymes & membranes made by rough ER, then processed in the Golgi
  • Some lysosomes bud from the trans Golgi
  • Some types of cell can engulf material by phagocytosis; this forms a food vacuole
  • A lysosome fuses with the food vacuole and digests the contents
  • Lysosomes also use enzymes to recycle the cell's own organelles and macromolecules, a process called autophagy

  
• Acid Hydrolases


  • Hydrolases optimal enzymatic activity only at an acidic pH
  • Protected from cleavage by high level of glycosylation and/or their 3-D shape (conformation) (GLYCOCALIX)
  • An H+ ATPase in the membrane pumps H+ into the lysosome, maintaining its lumen at an acidic pH
• Phagocytosis


  1. Cell engulfs material to form a food vacuole

  2. Lysosome fuses with food vacuole and digests contents

  
• Autophagy


  1. Activation of a signaling pathway initiates a nucleation event in the cytoplasm

  2. A crescent of autophagosomal membrane grows by fusion of vesicles

  3. Autophagosome fuses with lysosomes containing acid hydrolases that digest its content

  
• Autophagy


  • Selective autophagy is mediated by receptors that recruit cargo to the autophagosome membrane
  • Nonselective Autophagy Is Regulated by Nutrient Availability
• Lysosomal Storage Diseases


  • Gene for one of the hydrolytic enzymes of the lysosome may be not functional
  • Accumulation of the component that cannot be digested
  • Tay-Sachs disease: lipase is missing, leading to accumulation of lipids in the brain
  • Inclusion-cell disease (I-cell disease): almost all lysosomal enzymes are missing due to defective sorting to lysosomes (they are secreted), leading to inclusions of undigested substrates in the cell, with multi-organ disfunctions

  
• Vacuoles


  • Large vesicles derived from the ER and Golgi apparatus
  • Perform a variety of functions in different kinds of cells
  • Food vacuoles formed by phagocytosis in animal cells
  • Contractile vacuoles in many freshwater protists, pump excess water out of cells
  • Central vacuoles in plant cells, contain a solution called sap
  • Digestive vacuoles as plant lysosomes
  • Storage vacuoles for reserves
• How do plant cells grow?

  1. Localized weakening of cell wall → turgor-driven expansion and enlargement

  2. Uptake of water into an expanding vacuole. The cytosol is eventually confined to a thin peripheral layer, which is connected to the nuclear region by strands of cytosol stabilized by bundles of actin filaments

  
• Peroxisomes


  • Specialized metabolic compartments bounded by a single membrane
  • Contain enzymes that remove hydrogen atoms from various substances and transfer them to oxygen, forming hydrogen peroxide (H2O2)
  • Also contain catalase enzyme that converts H2O2 to water
  • Some use oxygen to break fatty acids into smaller molecules, eventually used for fuel for respiration
  • In the liver, they detoxify alcohol and other harmful compounds
  • Glyoxysomes in the fat-storing tissues of plant seeds, convert fatty acids to sugar to feed the emerging seedling
• 1. linked adrenoleukodystrophy (ALD)


  • Inherited single enzyme deficiency disorder
  • Mutations in the ABCD1 gene – encodes the adrenoleukodystrophy protein (ALDP), a peroxisomal integral membrane protein
  • Very long fatty acid oxidation in peroxisomes is dysfunctional → accumulation of very-long chain fatty acids
  • Myelin sheath tissue completely damaged and lost
  • Without myelin, nerves cannot conduct impulses properly
  • Lack of myelin –demyelination – destroys nerve cells in brain
• 'Lorenzo's Oil'


  • Mixture of rapeseed & olive oil (4:1 = erucic acid : oleic acid)
  • Reduces the levels of very long chain fatty acids
  • Must be used with low-fat diet
  • Especially effective in pre-symptomatic patients