Intracellular proteolysis Flashcards
Proteolysis
Break down of proteins with proteases by cleaving the peptide bond
What are metalloprotease?
Any protease enzyme whose catalytic mechanism involves a metal
For example Meltrin has a significant role in myogenesis which is the fusion of muscle cells during embryo development
Endopeptidases
Break peptide bond in the middle of the polypeptide
Exopeptidases and what type of enzymes does this include
Break of polypeptide from end of chain
These include Aminopeptidases and Carboxypeptidases
Why is protein degradation necessary?
Necessary to prevent the build up of unwanted protein and permitting the breakdown of amino acids
Phase 1 of protein degradation
- Forms thioester bond between end (COOH) group of ubiquitin and a cystein E1(HS) using ATP
- Transfer of Ubiquitin to cystein on to E2
- E3 transfer Ubiquitin from E2 to target protein
- Many different E3 enzymes exist for specific target proteins
Phase 2 of degreadation
Ubiquitinated proteins are degraded by a large complex known as the 26 proteasome.
What is the half life of proteins?
Time taken for protein to degrade the protein in half and measures how stable the protein is.
What is the N-end rule?
The N-terminal amino acid of a protein determines its half life
What is The SREBP cycle for?
• For cholesterol regulation
Protein activion of digestive enzymes?
○ An inactive precursor referred to as pro-proteins are cleaved to form the active protein.
○ Specific cleavage causes conformational changes which expose the active site
○ Inactive Chymotrypsinogen forms active π-chymotrypsin by a trypsin cleavage
○ Certain residues are removed at different positions resulting in the formation of active α-chymotrypsin and the fragments are held together with disulphide bonds.
Activation of clotting factors
○ Serine proteases and its glycoprotein co-factor are activated to become active components that then catalyse the next reaction
○ Factor 9 deficiency is the cause of X-linked Haemophilia
○ This ultimately results in a cross-linked fibrin
Enzymes involved in ubiquitulation
E1: Ubiquitin-activating enzyme
E2: Ubiquitin-conjugating enzyme
E3: Ubiquitin ligase
The SREBP cycle when cholesterol levels are low
○ Ubiquitin targets Insig for degradation
○ Secretory proteins escort SCAP/SREBP to golgi complex
○ In golgi, two proteases release regulatory domain of SREBP
○ The regulatory domain enters the nucleus and the transcription of lipid synthesizing enzymes are stimulated
This increases cholesterol synthesis
What does HIV-1 protease generate?
Generates 2 proteins:
Gag and Pol
