Amino Acids: Disposal of Nitrogen Flashcards
What is the main difference between AAs and fats/carbs?
They are NOT stored and it is important to dispose of them if they are in excess b/c can build up as ammonia (toxic)
What are 3 sources of AAs?
1) Diet
2) Protein that is ubiquitously degraded
3) Transamination
What is the most important route to dispose nitrogen?
Urea
What is the ubiquitin-proteasome proteolytic pathway?
- Ubiquitin tags proteins for death
- Proteasomes recognize ubiquitinated proteins
- Unfolds it, deubiquitinates it and transports it to its proteolytic core -> peptide fragments come out -> degraded to AAs in cytosol
- Whole process is ATP-dependent
Where does dietary protein digestion begin?
Stomach: HCl (denatures) and Pepsinogen (inactive zymogen)
-Pepsinogen -> Pepsin (active, first enzyme for digestion of proteins)
Why is pepsin unique?
Works really well at the very low pH of stomach
-Only works in stomach
What enzymes does the pancreas release during dietary protein digestion?
1) Enteropeptidase: activates trypsin -> key to activate rest of enzymes:
2) Elastase
3) Chymotrypsin
4) Carboxypeptidase A and B
In the small intestine you get down to free AAs, where do these get absorbed?
Most in the liver
What do all degradation digestive enzymes have in common?
- Cut peptide bonds to release AAs
- All begin as zymogens
- All required in combination
What is transamination?
Funneling of amino groups to glutamate
What happens in the alanine aminotransferase (ALT) rxn?
Alanine (alpha-amino acid) gives its amino group to Alpha-ketoglutarate
-Alpha-ketoglutarate becomes glutamate (by PLP) along with its alpha-keto partner pyruvate
What happens in the aspartate aminotransferase (AST) rxn?
AST funnels amino groups from alpha-ketoglutarate -> glutamate
- AST transfers amino group from glutamate to oxaloacetate -> aspartate
- Aspartate is used as a source of N in the urea cycle
What does elevated plasma AST and ALT indicate?
Elevated in nearly all liver disease
-Could be from viral hepatitis, toxic injury, prolonged circulatory collapse
What is pyridoxal phosphate (PLP)?
Coenzyme of transamination rxns
-Requires Vitamin B6
What are the 3 enzymes that can fix ammonia into an organic compound?
1) Glutamate dehydrogenase
2) Glutamine synthetase
3) Carbamoyl phosphate synthase I
Where is glutamate dehydrogenase found? How does it fix ammonia?
In liver and kidney; fixes ammonia to alpha-ketoglutarate -> glutamate
-Oxidative deamination -> free ammonia
What are the 2 ways we can transport ammonia to the liver?
1) Glutamine synthetase combines ammonia w/ glutamate (adds an additional amino group) -> Glutamine (end has an amide instead of a carboxylic acid)
2) Transamination of pyruvate -> Alanine
What does glutaminase do?
Glutamine -> Glutamate
- Releases free ammonia
- Useful to eliminate ketoacidosis: ammonia pick up extra proton, make ammonium ion and release in urine
Where is there a high concentration of glutamine synthetase?
Skeletal muscle, liver, and CNS
-Glutamine found in plasma at concentrations higher than other AAs
What is the top concern of hyperammonemia?
Neurotoxicity: tremores, slurring of speech, somnolence (drowsiness), vomiting, cerebral edema, and blurring of vision
-At high concentrations -> death
Where are the rxns of the urea cycle?
1st 2 in mitochondria, rest in cytosol (in the liver)
What does urea look like?
1 C (from CO2) + 2 N (1 from free ammonia, 1 from aspartate)
What is the reaction that starts the urea cycle?
Carbamoyl phosphate synthase I fixes ammonia (using 2 ATP) -> Carbamoyl phosphate
What does the actual making of urea come from?
Breakdown of Arginine by Arginase
