Case2

Question 1

explain the process of intracellular vesicular trafficking

Answer 1

1. exocytosis
   
   1. N vs O linked
   2. er->golgi-> extracellular (olink) or cytosolic(Nlinked)
2. endocytosis
   
   1. endosome
      
      1. early
      2. late

Question 2

explain how lysosomal enzymes are delivered into lysosomes

Answer 2

N-linked oligosaccharide processing

1. protein/oligosacchardie synthesis begins in the ER
   
   1. oliosaccharide is built on dolichol one sugar at a time by glycosyltransferases
   2. oligosaccharide brach is consrtucterd and attached to amide nitrogen of and asparganine of protein by
2. oligosaccharides are added and trimmed, then moved to golgi
   
   1. processing by the removal of specific mannosyl and glucosyl residues as the glycoprotein moves through the rER.
3. golgi further trims and addition of further monsacchardies
   
   1. sugar moeities ar completed in the golgi with mannoses and fucoses
   2. N-linked glycoproteins are phorylated on carbon 6 of one or more mannsyl residues, via UDP-GlcNAc (phosphotransferase).
4. leaving to the targeted area
   
   1. receptors, located in the golgi membrane, bind the mannose 6-phosphate residues of these proteins, which are then packeged into vesicles and sent to the lysosomes.

Question 3

list structural differences between different types of oligosaccharides

Answer 3

oligosaccharide (glycan) is the component of glycoprotein. These are enzymatically attached to protein linkage

Two types of linkages

1. Olinked
   
   1. attached to the hydroxyl group of S and T
   2. example
      
      1. ABO groups
         
         1. terminal glycan is GalNAc, blood group=A
         2. Terminal glycan is Galactose,bloodgroup=B
         3. neither Gal or GalNAc ins blood group=o
2. Nlinked
   
   1. attached to the amide group of the (asparganinge)
   2. Branched structure
   3. mannose rich or complex

Question 4

recognize LSD based on enzyme assays

1. disease
   
   1. dificiency
   2. assays
      
      1. urine,plasma,fibroblasts and leukocytes

Answer 4

1. mucopolysaccharidoses- hurler and hunter
   
   1. deficiency
      
      1. inability to degrade GAG
      2. subtypes
         
         1. hunter
            
            1. lack iduronate sulfatase
               
               1. removes sulfer from iduronic sugar on GAG(DS or KS)
            2. less severe than mucopolysaccharidosis
         2. hurler
            
            1. lack a-liduronidase
               
               1. rate limiting step,removes iduronic sugar group from GAG
            2. mirrors mucopolylipidosis
   2. metabolites
      
      1. plasma
         
         1. higher GAGs
      2. fibroblast
      3. peripheral leukocytes
      4. urine
         
         1. GAGs present
2. sphingolipidoses
   
   1. deficiency
      
      1. inability to degrade plasma membrane sphigolipids
   2. metabolites
      
      1. plasma
         
         1. higher number of sphingolipids
      2. fibroblast
      3. peripheral leukocytes
3. pompe disease
   
   1. deficiency
      
      1. inability to degrade glycogen
   2. metabolites
      
      1. fatty liver
         
         1. build up of glycogen in the liver
      2. enzyme screening leads to lack of function in assay
4. mucopolipidosis 2
   
   1. deficiency
      
      1. inability to phosphorylate mannose in the in the golgi
   2. metabolites
      
      1. plasma
         
         1. elevated enzymes
      2. fibroblast
         
         1. decreased enzyme levels
      3. peripheral leukocytes
         
         1. enzymes are normal except “N-acetylglucosamine-1-phosphotransferase”
      4. urine
         
         1. oligosaccharides present in urine

Question 5

Differentiate single lysosomal enzyme deficiencues from a complex lysosomal disease

Answer 5

1. simple
   
   1. one enzyme is affected
   2. example
      
      1. hunter, hurler
2. complex
   
   1. multiple enzymes are affected
   2. example
      
      1. ML2

Question 6

what enzymes are present in lysosomes

Answer 6

1. hydrolases
2. sulfases
   3.