Amino Acids: Disposal of Nitrogen

Question 1

What is the main difference between AAs and fats/carbs?

Answer 1

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)

Question 2

What are 3 sources of AAs?

Answer 2

1) Diet
2) Protein that is ubiquitously degraded
3) Transamination

Question 3

What is the most important route to dispose nitrogen?

Answer 3

Urea

Question 4

What is the ubiquitin-proteasome proteolytic pathway?

Answer 4

• 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

Question 5

Where does dietary protein digestion begin?

Answer 5

Stomach: HCl (denatures) and Pepsinogen (inactive zymogen)

-Pepsinogen -> Pepsin (active, first enzyme for digestion of proteins)

Question 6

Why is pepsin unique?

Answer 6

Works really well at the very low pH of stomach

-Only works in stomach

Question 7

What enzymes does the pancreas release during dietary protein digestion?

Answer 7

1) Enteropeptidase: activates trypsin -> key to activate rest of enzymes:
2) Elastase
3) Chymotrypsin
4) Carboxypeptidase A and B

Question 8

In the small intestine you get down to free AAs, where do these get absorbed?

Answer 8

Most in the liver

Question 9

What do all degradation digestive enzymes have in common?

Answer 9

• Cut peptide bonds to release AAs
• All begin as zymogens
• All required in combination

Question 10

What is transamination?

Answer 10

Funneling of amino groups to glutamate

Question 11

What happens in the alanine aminotransferase (ALT) rxn?

Answer 11

Alanine (alpha-amino acid) gives its amino group to Alpha-ketoglutarate
-Alpha-ketoglutarate becomes glutamate (by PLP) along with its alpha-keto partner pyruvate

Question 12

What happens in the aspartate aminotransferase (AST) rxn?

Answer 12

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

Question 13

What does elevated plasma AST and ALT indicate?

Answer 13

Elevated in nearly all liver disease

-Could be from viral hepatitis, toxic injury, prolonged circulatory collapse

Question 14

What is pyridoxal phosphate (PLP)?

Answer 14

Coenzyme of transamination rxns

-Requires Vitamin B6

Question 15

What are the 3 enzymes that can fix ammonia into an organic compound?

Answer 15

1) Glutamate dehydrogenase
2) Glutamine synthetase
3) Carbamoyl phosphate synthase I

Question 16

Where is glutamate dehydrogenase found? How does it fix ammonia?

Answer 16

In liver and kidney; fixes ammonia to alpha-ketoglutarate -> glutamate
-Oxidative deamination -> free ammonia

Question 17

What are the 2 ways we can transport ammonia to the liver?

Answer 17

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

Question 18

What does glutaminase do?

Answer 18

Glutamine -> Glutamate

• Releases free ammonia
• Useful to eliminate ketoacidosis: ammonia pick up extra proton, make ammonium ion and release in urine

Question 19

Where is there a high concentration of glutamine synthetase?

Answer 19

Skeletal muscle, liver, and CNS

-Glutamine found in plasma at concentrations higher than other AAs

Question 20

What is the top concern of hyperammonemia?

Answer 20

Neurotoxicity: tremores, slurring of speech, somnolence (drowsiness), vomiting, cerebral edema, and blurring of vision
-At high concentrations -> death

Question 21

Where are the rxns of the urea cycle?

Answer 21

1st 2 in mitochondria, rest in cytosol (in the liver)

Question 22

What does urea look like?

Answer 22

1 C (from CO2) + 2 N (1 from free ammonia, 1 from aspartate)

Question 23

What is the reaction that starts the urea cycle?

Answer 23

Carbamoyl phosphate synthase I fixes ammonia (using 2 ATP) -> Carbamoyl phosphate

Question 24

What does the actual making of urea come from?

Answer 24

Breakdown of Arginine by Arginase