4.2 nitrogen metabolism

Question 1

Amino acids can be _______ or Amino acid carbons can be converted to ________

Answer 1

oxidized
glucose

Question 2

Nitrogen removed from Amino acids form _____

Answer 2

NH4+

Question 3

Is NH4+ toxic?

Answer 3

yes, thats why it needs to be removed through urea cycle

Question 4

How is dietary protein digested?

Answer 4

1. protein ingested
2. Gets ingested by proteases → gives us di/tri-peptides
3. Uptaken by intestinal epi cells → digested and released as AA
4. Most AA are taken up by Na+ symporter, Na+ recycled through antiporter
5. AA released into bloodstream by facilitated diffusion

Question 5

______ is the major product from the breakdown of amino acids and it exists as _____ and neutral pH

Answer 5

Ammonia (NH3+), Ammonium (NH4+)

Question 6

what can accumulation of NH4+ be caused by?

Answer 6

failure in urea cycle, inborn errors in metabolism, bacterial infection

Question 7

when you remove an amino group from amino acid and add it to alpha ketoglutarate you get ______

Answer 7

glutamate

Question 8

the best way to re-utilize nitrogen is by _______

Answer 8

making proteins

Question 9

what is the most important transamination step?

Answer 9

transamination of amino group from amino acid –> α-ketoglutarate to generate glutamate

Question 10

Oxidative deamination

Answer 10

glutamate —> a-ketoglutarate

• enzyme = glutamate dehydrogenase
• electrons go from NAD/NADP –> NADH/NADPH
• Ammonium produced
• a-ketoglutarate can now go back and do transamination rxn again

Question 11

_______ is the combined actions of aminotransferases and glutamate dehydrogenase

Answer 11

transdeamination

Question 12

how does transdeamination work?

Answer 12

1. amino group gets transferred from AA → a-ketoglutarate to make glutamate
2. glutamate → a-ketoglutarate= release of NADH and NH4+
   
   1. NADH + NH4+ = urea which now goes to liver

Question 13

_____ is the major N-donor, the rest is done by _____-

Answer 13

glutamate, glutamine

Question 14

what can be done with glutamate?

Answer 14

1. glutamate → NH4+ → urea cycle in liver
   
   1. glutamate → aspartate → urea cycle

Question 15

where is glucose-alanine cycle found?

Answer 15

muscle

Question 16

steps of glu-alanine/Cahill cycle?

Answer 16

1. Pyruvate made because exercise
2. glutamate will donate amino group to pyruvate (transamination)→ Alanine
3. Alanine will enter bloodstream and bring Nitrogen to liver→ Alanine loses amino group to a-ketoglutarate →
4. Glutamate that is regenerated will donate amino group/synthesis of aspartate → goes through urea cycle
5. Alanine loses amino group → pyruvate
   
   1. Pyruvate can go through gluconeogenesis → glucose, now cycle can go again

Question 17

Transport of AA nitrogen to liver by Peripheral tissue

Answer 17

1. a-ketoglutarate → Glutamate (by GDH)
2. Glutamate takes up nitrogen from ammonium → glutamine (by glutamine synthetase)
3. Glutamine → mitochondria of liver
4. Glutaminase removes one amino group in form of Ammonium → Glutamate
5. Glutamate goes through oxidation → release another ammonium OR will make aspartate
6. Goes through urea cycle

Question 18

glutamine can carry ____ nitrogen, alanine can carry ____

Answer 18

2, 1

Question 19

steps of urea cycle

Answer 19

1. Bicarbonate + Ammonium → Carbamoyl phosphate
   
   1. by CPS1
      
      1. uses 2 ATP
2. Carbamoyl phosphate + Ornithine → Citrulline
   
   1. by Ornithine transcabamoyalse
   2. displaced organic phosphate
3. Citrulline → exported to cytosol (exchanged for another molecule of Ornithine)
4. Citrulline (1 Nitrogen) + Aspartate (1 nitrogen)→ Argininosuccinate (2 nitrogen)
   
   1. by Argininosuccinate synthetase
   2. uses 1 ATP
5. Argininosuccinate →Arginine + Fumarate
   
   1. Fumarate is cleaved off, goes to TCA cycle
   2. by Argininosuccinate lyase
6. Arginine → Urea + Ornithine
   
   1. by Arginase
   2. Infants lack arginine

Question 20

3 ways for disposal of ammonia?

Answer 20

1. Urea by urea cycle
2. glutamine
3. alanine

Question 21

how can urea be regulated?

Answer 21

Allosterically regulation of CPS1 by NAG

Question 22

explain the regulation of CPS1

Answer 22

• NAG positively regulates CPS1(more NAG = more CPS1 rxns)
• Arginine regulates NAG, arginine made in urea cycle activates cycle more

Question 23

disorder of urea cycle

Answer 23

defect in Ornithine Transcarbamoylase (OTC) (urea cycle comes to a stop bc doesnt make citruline)

Question 24

______ is an autoimmune disorder that can also affect urea cycle

Answer 24

hepatitis