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22 Cards in this Set
- Front
- Back
What is a Proteosome
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A large multi-protein complex that is involved in breakdown of damaged or unnecessary proteins
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Three steps in proteosome breakdown of proteins
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1: Receptor on "lid" recognizes multiubiquitin chain bound to target
2: Protein is unfolded and fed into proteasome 3: Polypeptide chain is degraded into small peptides and amino acids that can be recycled |
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Mammals have:
? E1 enzymes? ? E2 enzymes? ? E3 proteins? |
1 E1 enzyme
30 E2 enzymes >100 E3 proteins |
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What do E3 proteins serve as in protein degradation?
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Specificity factors to bring a variety of different targets to a common structure that mediates their destruction
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Ubiquitin-Mediated Proteolysis Pathway has a role in:
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*Turnover of abnormal or damaged proteins
*Cell cycle control *Stress response *Peroxisome assembly *Antigen processing *Regulation of histone function *Viral Infection *Tissue degeneration *Cell differentiation |
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Neurological disorders involving accumulation of aggregates of misfolded or non-functional proteins:
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*Alzheimer's Disease
*Prion-related diseases |
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Parkin
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*E3 ligase
*One of 3 mutated genes in Parkinson's Disease *Mutations inactivating Parkin lead to accumulation of aggregates of proteins |
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Lysosome
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Membrane-surrounded vesicles containing large varieties of hydrolytic enzymes capable of breaking down most biological molecules (proteases, lipases, nucleases, etc)
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Delivery of material to the lysosome occurs in 3 ways
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1: Endosomes
2: Autophagy 3: Phagocytosis |
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Endosomes
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Membrane vesicles that are taken up by endocytosis. Fuse with lysosome adn deposit material for destruction
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Autophagy
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Process by which cells digest own organelles. Defective organell is surrounded by membrane-bound endoplasmic reticulum resulting in an AUTOPHAGOSOME, which fuse with lysosome and deposit organelle for degradation
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Phagocytosis
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Endocytosis on a large scale. Large particles (viruses, bacteria, dead cells) are engulfed into large vesicles which then fuse with lysosome.
*Carried out by Macrophages and Neutrophils |
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Macrophages are involved in
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Phagocytosis. Engulf large particles and fuse with lysosomes
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Defective lysosomal function can lead to
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Tay-Sachs disease
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Tay-Sachs Disease
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Lack of functional lipases within lysosomes of nerve cells leads to massive lipid accumulation in these defective lysosomes, and eventual impaired nerve function.
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2 Main mechanisms by which cells in multi-cellular organisms die
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1: Necrosis
2: Apoptosis |
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Necrosis
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Pathological response to acute cell injury
*Lysis of membrane - materials spill out *Mitochondria swell and rupture *General inflammatory response triggered |
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Apoptosis
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Normal physiological response to suicide signals, or a lack of survival signals
*Chromatin condensation *Cytoplasm shrinks without membrane rupture *Cell contents packaged into membrane bound bodies, with functional organelles that may be engulfed and used by neighboring cells *Epitopes on plasma membrane appear that attract phagocytes |
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Functions of Apoptosis
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*Limb development: Sculpts structures
*Neuronal development: Neurons that fail to contact target apoptose *Regulation of cell number *A response to DNA damage or cell damage that can't be repaired *Response to excessive proliferative signals *Removal of virally infected cells |
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Mechanism of apoptosis initiated OUTSIDE the cell
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Killer lymphocytes recognize foreign molecules displayed on surface of the cells destined to die
*They recruit intracellular adaptor proteins that aggregate procaspase molecules *These procaspase molecules cleave and activate each other |
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Apoptosis initiated INSIDE the cell
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Stressed cells are induced to release cytochrome C out of the mitochondria and into the cytoplasm where it binds to adaptor molecules and activates caspases
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Caspase Function
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*Caspases are proteases that are synthesized in the cell and maintained in their inactive form
*Upon activation, they cleave key components of the cell to initiate cell death *They also cleave each other, resulting in synergistic activation *Much like cells that respond to growth factors, this signal amplification step results in a unified cellular response |