disease

disease

1. mucolipidosis type II (I-cell disease)

   • eye problems
     • optic nerve needs high ATP
   • signal detected
     • expressed
       • transcribed in nucleus
         • translated in cytoplasm
           • co-translational protein processing
             • cytosolic proteins
               • remain in cytosol
               • targeted to organelles
             • ER signal sequence
               • secreted or organelle-targeted proteins
                 • secreted proteins have signal sequence targeting ribosome to ER
                 • nuclear proteins have specific AA sequence
                   • called nuclear localization signal sequence (NLS)
             • proteins modified "post-translationally"
               • individual AA phosphorylated
                 • phosphate added by kinase
               • sugar chains added (glycosylation)
                 • most common
                 • important in cell-cell recognition
               • polypeptide chain cleaved (proteolysis)
                 • ubiquitin added to protein to be degraded by proteasome
               • enter "endomembrane system" if destined for excretion or organelles
                 • Golgi apparatus
                   • modify proteins, sorts, and packages into labeled vesicles
                 • lysosomes
                   • contain hydrolytic enzymes that work at low pH
                     • enzymes destined for here have M6P tag
   • recessive genetic mutation
   • high levels of lysosome hydrolyses in blood
   • defective phosphotransferase is unable to transfer phosphate to mannose on proteins
     • not tagged for lysosome and are excreted

2. cystic fibrosis

   • lack of functional Cl- ion channel protein
     • thick mucus
       • passive diffusion
         • simple diffusion
           • through lipid bilayer
         • facilitated diffusion
           • through a protein
         • ion channels
           • gated, specific
         • aquaporins
           • passive membrane channel proteins
           • permit cellular waste flow
         • active transport
           • pump protein can transport against concentration gradient
             • low to high
           • uses ATP
   • recessive, loss-of-function mutation
   • abnormal, AQP5 (CF)

3. cancer

   • COLLECTION of diseases caused by unregulated cell division after multiple mutations
     • increased cell division
     • decreased apoptosis
   • ignore normal cell cycle checkpoints
     • tumor-suppressor genes (brakes)
       • function can be lost
         • mutation in TS gene
         • DNA methylation near its promoters
         • aneuploidy
     • proto-oncogenes (accelerator)
       • make proteins that allow cell division
       • mutations create oncogenes (OVERACTIVE)
   • two-hit hypothesis (sporadic)
     • person w/ 2 functional alleles of TS gene accumulates 2 mutations
   • familial
     • person w/ 1 inherited mutant picks up 1 more mutation in TS gene