Protein Degradation Flashcards
Two systems of protein degradation
extracellular
intracellular
EC Protein Degradation
diet: proteins –> epithelial cells of SI (absorption)–> liver (by the portal vein for processing): AAs
4 steps of protein catabolism
- 1) degradation of proteins to AAs
- 2) removal of AA group
- 3) elimination of ammonia (urea)
4) fate of the carbon chain…
Which can be stored?
fat, carb, protein
only fat and carb can be stored (protein/AAs/ammonia cannot be stored)
What happens to AAs of protein?
Carbon chain goes for storage but NH3 gets excreted
What are 2 roles of trypsin?
cut proteins in diet; cut other proteases (zymogens)
-lacks protein target specificity
Why is no ATP required for absoprtion of proteins?
Acidity of gut environment
In cells, you need ATP to de-fold proteins
Describe the transamination reaction
take nitrogen group from alpha amino acid from diet and add it to glutamate using AMINOTRANSFERASE (multiple)
*converted AA to ketoacid, which is basically a carbon chain
- no energy requirement,
- fully reversible
- no energy needed
What is the essential co-factor required for transamination reaction?
pyridoxal phosphate (B6 derivative)
What are the 3 important AA/Ketoacid pairs (that feed into TCA)?
1) glutamate alpha-ketoglutarate
2) alanine pyruvate
3) aspartate oxaloacetate
What is the role of “glutamate alpha-ketoglutarate” ?
transamination
What is the role of alanine pyruvate?
glucose-alanine cycle: capture of ammonia in peripheral tissue and safe transportation of that ammonia to the liver
What is the role of aspartate oxaloacetate?
urea cycle (donates second nitrogen into the cycle)
Why the tight coupling btwn AA breakdown and TCA?
energy requirement (depletion)
these are the sensors to tell you time to start breaking down protein:
1) glutamate alpha-ketoglutarate
2) alanine pyruvate
3) aspartate oxaloacetate
What is arginine’s effect on S-ethyglutamate (cofactor for CPS1)?
stimulates as [arg] increases
CPS1
rate limiting factor in pathway
Why is the urea cycle irreversible?
1) energy requirement
2) compartmentalized
How is urea cycle regulated?
-positively regulated:
arg positively regulates cofactor for CPS1 (RLS enzyme)
What is the nitrogen source for the urea cycle?
glutamate (directly and indirectly)
What is the net effect in step(s) of urea cycle?
hyperammonenemia
eg: Mutation in CPS1
What is the physiological response to sudden “pulse” of ammonia?
1) attach ammonia to pyruvate and make alanine –> transport to liver –> catalyze hydrolysis there
What are key enzymes only expressed in liver?
asparginase, glutaminase, arginase, CPS1
Which reactions require: Vitamin B6 (pyridoxal phosphate)?
x
Which reactions require: S-adenosyl methionine?
x
