4.2 nitrogen metabolism Flashcards
Amino acids can be _______ or Amino acid carbons can be converted to ________
oxidized
glucose
Nitrogen removed from Amino acids form _____
NH4+
Is NH4+ toxic?
yes, thats why it needs to be removed through urea cycle
How is dietary protein digested?
- protein ingested
- Gets ingested by proteases → gives us di/tri-peptides
- Uptaken by intestinal epi cells → digested and released as AA
- Most AA are taken up by Na+ symporter, Na+ recycled through antiporter
- AA released into bloodstream by facilitated diffusion
______ is the major product from the breakdown of amino acids and it exists as _____ and neutral pH
Ammonia (NH3+), Ammonium (NH4+)
what can accumulation of NH4+ be caused by?
failure in urea cycle, inborn errors in metabolism, bacterial infection
when you remove an amino group from amino acid and add it to alpha ketoglutarate you get ______
glutamate
the best way to re-utilize nitrogen is by _______
making proteins
what is the most important transamination step?
transamination of amino group from amino acid –> α-ketoglutarate to generate glutamate
Oxidative deamination
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
_______ is the combined actions of aminotransferases and glutamate dehydrogenase
transdeamination
how does transdeamination work?
- amino group gets transferred from AA → a-ketoglutarate to make glutamate
- glutamate → a-ketoglutarate= release of NADH and NH4+
- NADH + NH4+ = urea which now goes to liver
_____ is the major N-donor, the rest is done by _____-
glutamate, glutamine
what can be done with glutamate?
- glutamate → NH4+ → urea cycle in liver
- glutamate → aspartate → urea cycle
where is glucose-alanine cycle found?
muscle
steps of glu-alanine/Cahill cycle?
- Pyruvate made because exercise
- glutamate will donate amino group to pyruvate (transamination)→ Alanine
- Alanine will enter bloodstream and bring Nitrogen to liver→ Alanine loses amino group to a-ketoglutarate →
- Glutamate that is regenerated will donate amino group/synthesis of aspartate → goes through urea cycle
- Alanine loses amino group → pyruvate
- Pyruvate can go through gluconeogenesis → glucose, now cycle can go again
Transport of AA nitrogen to liver by Peripheral tissue
- a-ketoglutarate → Glutamate (by GDH)
- Glutamate takes up nitrogen from ammonium → glutamine (by glutamine synthetase)
- Glutamine → mitochondria of liver
- Glutaminase removes one amino group in form of Ammonium → Glutamate
- Glutamate goes through oxidation → release another ammonium OR will make aspartate
- Goes through urea cycle
glutamine can carry ____ nitrogen, alanine can carry ____
2, 1
steps of urea cycle
- Bicarbonate + Ammonium → Carbamoyl phosphate
- by CPS1
- uses 2 ATP
- by CPS1
- Carbamoyl phosphate + Ornithine → Citrulline
- by Ornithine transcabamoyalse
- displaced organic phosphate
- Citrulline → exported to cytosol (exchanged for another molecule of Ornithine)
- Citrulline (1 Nitrogen) + Aspartate (1 nitrogen)→ Argininosuccinate (2 nitrogen)
- by Argininosuccinate synthetase
- uses 1 ATP
- Argininosuccinate →Arginine + Fumarate
- Fumarate is cleaved off, goes to TCA cycle
- by Argininosuccinate lyase
- Arginine → Urea + Ornithine
- by Arginase
- Infants lack arginine
3 ways for disposal of ammonia?
- Urea by urea cycle
- glutamine
- alanine
how can urea be regulated?
Allosterically regulation of CPS1 by NAG
explain the regulation of CPS1
- NAG positively regulates CPS1(more NAG = more CPS1 rxns)
- Arginine regulates NAG, arginine made in urea cycle activates cycle more
disorder of urea cycle
defect in Ornithine Transcarbamoylase (OTC) (urea cycle comes to a stop bc doesnt make citruline)
______ is an autoimmune disorder that can also affect urea cycle
hepatitis
