lysosomes and proteosomes Flashcards
de Duve
discovered lysosomes through differential gradient centrifugation
- “injured” (homogenized) = hydrolytic
- lysosomes co-sedimented with mitochondria
lysosomes
a) 50+ hydrolytic enzymes
- degrade nearly all molecules
- e.g nucleases, phosphatases, proteases
b) single membrane bound
c) pH 5 = optimal
acid phosphatase
marker enzyme for lysosomal identification
- cleaves phosphates from proteins
- works best in acidic environments
heterophagy
- most closely associated with lysosomes
- Rudolph Virchow - looked at pus, thought WBC were giving birth to RBC
- Elie Metchnikoff - phagocytosis, discovered WBCs prevent disease
cell consumes (eats) material
opsinization
antibodies tag a bacterium and the Fc region of the antibody binds to the Fc receptor for phagocytosis
ex: leukocytes have these receptors
Myasthenia Gravis
- autoimmune disease
- acetylcholine receptors are internalized and degraded = impaired muscle contraction
- antibodies form against nicotinic acetylcholine synapse receptors
curare
plant poison
- antagonist of nicotine Ach receptor
- blocks Ach receptor
- increased symptoms
drug = vyvgart
eserine
- inhibits breakdown of acetylcholinesterase
- relieved symptoms in patients
Torpedo Rays
- electroplax
- used to generate anti-Ach antobodies
- highest code of Ach-R
- when injected into mice, caused droopy eyelids
- indicated MG may be an autoimmune disease
3H bungarotoxin
- binds to Ach-R
- showed their were fewer number of receptors on postsynaptic component of neuromuscular junction
autophagy
- self digestion and has to do with cell death
- mitophagy –> aging
- LC3 mediates autophagy
chloroquine
autophagy lysosomal drug
- increases pH of lysosome which decreases its activity
- used to sensitize cancer cells to chemo drugs (cisplatin), but harms normal cells too
- cisplatin blocks nuclear DNA repair process –> apoptosis
specialized lysosomes
acrosome + plant vacuole
plant vacuoles serve as “lysosomes”
Silicosis (Miner’s disease)
- lungs become less elastic because of collagen deposition
- silica particles are sharp
- they enter the lungs and lysosomes, causing leak of hydrolytic enzymes = cells die
fibrosis : collagen secreted due to an injury
- decreases CO2/O2 exchange and elasticity of the lungs
chloroquine retinopathy/myopathy
- drug induced lysosomal disease
- not heritable
inherited lysosomal diseases
- 70 different types of storage diseases
- treated with enzyme replacement therapy
Tay Sachs Disease
inherited lysosomal disease
- Hex A deficiency
- can’t break down ganglioside GM2 –> accumulates in the brain
Hurlers Syndrome (Gargoylism)
inherited
- cis golgi
- gangliosides accumulate –> large lysosomes
- “co-culture” experiment “conditioned medium”
- Hurler cells look normal when put in culture with normal cells
- drug = Aldurazyme (ERT)
I cell disease
inherited
- cis golgi
- lots of hydrolases in the extracellular medium
- I cells can endocytose - M6P is ok
- I cell lysosomal enzymes can’t be endocytosed in normal fibroblast - M6P tag wasn’t added
Pompe’s Disease
- cis golgi
- defect in acid alpha glucosidase
- buildup of glycogen
- muscular generative disease
- myozyme = ERT drug
Gaucher’s Disease
inherited
- cis golgi
- lysosomal disease
- deficiency in glucocerebrosidase
- leads to enlargement of spleen and erosion of the long bones
- cerezyme - ERT drug
lysosomes
- degrades all molecules
- is an organelle
proteasomes
- degrades only proteins
- “particles” - “machine”
- large (750,000 Daltons)
- 30,000 per cell - target for cancer
- Velcade - blocks proteasomes and inhibits protease activity
- ubiquinated
- mutant yeast without proteasomes –> die
velcade
proteasome drug that targets cancer
