Amino Acid Metabolism: Protein Degradation Flashcards
(38 cards)
3 ways to breakdown protein and amino acids
- Lysosomes
- Digestive enzymes
- Ubiquitin/Proteasome
Properties of protein, kcal, how its regulated and syntheses
Energy Production (4 kcal/gm)
Regulation of Glucose Levels
Fatty Acid Biosynthesis
Ketone Body Synthesis
Digestive enzyme: Amino acids come from digestive enzyme, name four
Pepsinogen
Trypsin
Chymotrypsin
Carboxypeptidases
How are amino acids transported, in digestive enzymes
Sodium-dependent amino acid Symporters Transport AA across the intestinal epithelia.
Active Protease Catalytic Triad, 3 chains held it together by disulfides to protect it from harsh environments
Where are amino acids transported to?
amino acids are relatively soluble
Transported in blood to other tissues
Lysosomes: breakdown and recycling of cellular components. Describe ph, membrane characteristics and acidic hydorlases
Lysosomal Hydrolases:
Optimal activity at pH 5
Lysosomal Membrane Proteins: Most are heavily glycosylated to prevent breakdown
Transport Proteins: Protein Import and Export of Products Proteins for membrane fusion: Allow vesicles to fuse
Acidic hydrolases: Lipases, Amylases, Proteases, Nucleases
Lysomal protein pump
Lysosomal Substrates process
Degrade cellular materials
Recycle damaged organelles
Starvation response
Autophagy engulfs around proteins in intracellular
Ubiquitin-Proteasome System,the major protein degradation system. Try to name the major components, seven.
Proteasome is a macromolecular machine designed for protein degradation
Proteasome is the major route for the degradation of intracellular proteins
Protein quality control
Also has thiorse in the macromolecule!
Removal of damaged or misfolded proteins
Cell Cycle
Progression Destruction irreversible – inactivation complete Transcriptional Regulation Immune Response Surveillance for Foreign Antigens
How is ubiquitan similar to tied knots? Where can it be found? Length and nature?
It has the basic knot to which it is an ubiquitan subunit.
Ub - 76 residue protein (8.5 kDa)
Found only in eukaryotes
Very Highly Conserved
Covalently attached to proteins including other Ubn’s to build a poly-Ub chain
What is Ubiquitylation of a Protein?
Communicates a change in Protein Location, Conformation, Activity, Binding partners, or Stability
How is ubiquitin more than protein degradation?
It has numerous signals.
K 63
Target damage DNA
K 11 linked
Target cell cycle
K 48
Target protein degradation
Two ways AMPK is regulated
- activity is allosterically regulated by AMP levels and phosphorylation.
- AMPK enzyme levels are also regulated by Ubiquitylation
Ubiquitylation does..
Protein Conformation Ligand Binding Enzyme Activity Protein-Protein Interactions Cellular Location Protein Stability/Lifetime
Overall changes the landscape of proteins
Phosphorylation does..
Protein Conformation
Ligand Binding
Enzyme Activity (Activates AMPK)
Protein-Protein Interactions
Draw Ubiquitin-Transfer Pathways please
:)
E1: Ubiquitin Activating Enzyme
•First forms a Ubiquitin-AMP intermediate with release of PPi •Then a covalent E1~Ubiquitin thioester
E2: Ubiquitin Conjugating Enzyme
•Carries activated Ubiquitin as a covalent thioester conjugate •Share a conserved core domain of ~150 amino acid residues
E3: Ubiquitin Ligase
- Catalyzes the transfer of Ubiquitin to a Lys residue on a target protein
- Humans have more E3 Ubiquitin ligases than Kinases
How does Deubiquitinases (DUBs) catalyze the removal of Ub
Ubiquitin E3 ligase –covalently modifies proteins with Ub
Deubiquitinase – hydrolyzes isoamide bond between Ub and a target protein, or between linked Ub subunits
Human Genome ~ 100 DUBs
How long does ub has to be in order to be broken down by k 48?
Ub chain needs to have at least 4 Ub subunits
chains can grow much longer
Rate of Protein Degradation by the Proteasome is quicker in shorter ub chains
Three parts of Ubiquitin-Proteasome System
19S Particle: Composed of a Lid and a Base
20S proteasome
b-subunits are THR proteases with 3-different specificities
