Lecture 22 Flashcards
What was the first protein ever sequenced?
insulin
What is proopiomelanocortin?
A prohormone that is cleaved in a lot of different tissues to make different hormones such as ACTH
How long is proinsulin and what peptides does it have?
86 AA
- A, B, C
Where is insulin cleaved into mature form and what side chains does it have at this point?
- Golgi apparatus
- A and B (proteinases cleave C)
Where do trypsin-like enzymes cleave?
At the C terminus at basic residues like lysine and arginine
Where do carboxypeptidase-like enzymes cleave?
They cleave one AA at a time near the C end
What occurs in Familial Hyperproinsulinemia and why?
- too much proinsulin in the blood
- Autosomal dominant
- due to defective proinsulin cleavage resulting in equal amounts of proinsulin and insulin
Why is the C peptide in proinsulin useful?
It stays in the blood for a longer time than the other cleaved peptides sop its concentration is proportional to insulin production.
- useful in distinguishing between type 1 and type 2 diabetes
- measures endogenous levels of insulin because artificial insulin doesn’t have the C peptide
What is the difference between type 1 and type 2 diabetes?
- type 1 doesn’t make enough insulin
- type 2 is resistant to insulin
What is fictitious hypoglycemia?
- when people over treat themselves with insulin
How is pepsinogen activated?
Hydrogen ions
What is caspases?
apoptosis
What method does polio virus use to intiate protein synthesis?
IRES method instead of CAP dependent scanning
How does polio virus highjack the cell machinery?
Polio virus protease 2A cleaves eIF4G which is required for CAP dependent scanning initiation of protein synthesis BUT since polio doesn’t fuck wit CAP it stops the cell from making any proteins and then uses the cleaved eIF4G for IRES-mediated initiation. So it clears cellular ribosomes of any cellular tasks.
What does protein disulfide isomerase do?
It shuffles disulfide crossings combinations
What does peptidyl prolyl isomerase do?
interconvert CIS and trans forms of proline
What do chaperones do?
Discourage improper interactions lol naturally
When is the turnover rate of proteins elevated and why?
During starvation and hypercatalic states due to cortisol induction of ubiquitin-mediat3ed proteolysis
What are the two extracellular mechanisms for protein turnover?
- proteases
- amino and carboxy- peptidases
What are the intracellular mechanisms for protein turnover?
- proteasome-ubiquitin (most important and require ATP)
- caspases (involved in apoptosis)
How does the proteasome-ubiquitin system work?
- chain of ubiquitin attach to lysine residues on the protein which tarts that protein to the proteasome
Listen carefully.
I want you to describe the process of ubiquination, in detail.
1) enzyme E1 uses ATP to attach to ubiquitin
2) ubiquitin gets transferred to E2
3) ubiquitin gets transferred to the target protein via E3 catalyzation
4) ubiquitin goes to a proteasome who digests the protein and frees ubiquitin unharmed.
What is the N-end rule?
The nature of the N end has determinant properties regarding the proteins stability
If the N-end is serine how long is the protein stable for?
20 hours
If the N-end is aspartame how long is the protein stable for?
3 minutes
What is a PEST sequence?
(proline, glutamate, serine, threonine) sequence that causes the protein to be degraded more rapidly by ubiquitin system
What is the cause of Cystic Fibrosis?
- a 3 nucleotide deletion (phenylalanine) that causes the cystic fibrosis transmembrane receptor to misfold.
What is the actual purpose of the C peptide?
To hold the A and B peptide in the correct formation for them to correctly form sulfide bridges
How is insulin formed?
- signal sequence at the N end gets cleaved by signal peptidase
- disulfide bridges are formed between peptides A and B
- C peptide is cleaved via proteinases in the Golgi apparatus
