lysosomes

Question 1

structure amd function of lysosomes

Answer 1

100 lysosomes per cell

Single membrane  

Heterogeneous contents (lots of vesicles inside lysosomes) 

Acidic maintaining a pH of about 4-5 

pH is lowered by H+ pumps in the lysosome membrane  

Contains 40 hydrolytic enzymes (acid hydrolases), activated by proteolytic cleavage (hydrolysis of peptide bond)

Question 2

Extracellular substrate delivery to lysosomes

Answer 2

Fluid-phase endocytosis of molecules and lipoproteins (includes receptor-mediated endocytosis) ‘cell drinking’

Phagocytosis of particles 0.5 μm or more

Question 3

Intracellular substrate delivery to lysosome(Microautophagy)

Answer 3

Microautophagy is the direct uptake of soluble or particulate cellular constituents

Cytoplasmic substances translocate into lysosomes by direct invagination of the lysosome membrane 

Induced by rapamycin which inhibits mTOR. This inhibition mimics cellular starvation resulting in autophagy

Question 4

Intracellular substrate delivery to lysosomes(Macroautophagy)

Answer 4

Macroautophagy is cytosol or organelles wrapped around in a membrane which then fuse with lysosomes. § Double-membraned structures called autophagosomes enclose the material Non-selective macroautophagy is stimulated by cellular starvation.

Question 5

Receptor mediated endocytosis

Answer 5

Specific receptors on the surface of the lysosomes bind to the extracellular molecule

Plasma membrane region containing the receptor undergoes endocytosis forming a vesicle 

Molecules are transported to the lysosome and the receptors are recycled and placed back on to the cell membrane by exocytosis

Question 6

Targeting of lysosomal hydrolases to lysosomes

Answer 6

Lysosomal enzymes are delivered to endosomes in vesicles that bud from the TGN (Trans Golgi Network)

Lysosomal hydrolases are recognized in the TGN due to marker: mannose-6-phosphate which are added to N-linked-oligosaccharides as the lysosomal enzyme pass through Cis-Golgi-network 

Transmembrane M6P receptor proteins are present in TGN and binds to M6P at pH 5.6-6.7 

The hydrolases are packaged in Clathrin-coats (in the clathrin coated pits of the cytosolic side) and bud off the TGN (in a coat called retromer)

Question 7

Protein glycosylation in the ER

Answer 7

Translocation moves the imcomplete oligosaccharide across the membrane and completion of the core oligosaccharide occurs within the lumen of the ER

Precursors which contribute mannose and glucose to the growing oligosaccharide in the lumen are dolichol phosphate derivatives 

The core oligosaccharide is transferred from the dolichol phosphate to an Asn residue of the protein within the ER 

The core oligosaccharide is further modified in the golgi and the five sugar residue are retained in the final N-linked oligosaccharide

Question 8

I cell disease

Answer 8

Due to a single gene defect and is caused due to a recessive allele

All the hydrolases are missing from the lysosomes and are found in the blood as they’re unable to sort properly in the golgi apparatus  

They are secreted rather than transported to lysosomes 

Due to defective or missing GIcNAc phosphotransferase 

Lysosomal enzymes are not phosphorylated in the cis golgi network 

The M6P receptors do not segregate them into the appropriate transport vesicles in the TGN 

Instead, the lysosomal hydrolases are carried to the cell surface and secreted

Question 9

symptoms of i cell disease

Answer 9

Skeletal abnormalities

Developmental delay 

Enlarged liver and spleen 

Impaired hearing 

Death from pneumonia or congestive heart failure