13- Amino Acid Metabolism Flashcards
What are the two products of aa catabolism
AA –> NH3(toxic) + carbon skeleton
What do the transaminase need to work?
Pyridoxal-P as coenzyme
comes from Vitamin B6
cerebral edema
if ammonia enters the brain.
what can the carbon skeleton be used for?
Used in glycolytic pathways
Also can be used to make other things like epinephrine.
In what two forms can NH3 be removed?
Urea (liver)
Ammonia (kidney)
What are the enzymes that break down amino acids?
transaminases
– removes amino group
One for each amino acid (so 20)
Urea and pathway to excretion
Two amino groups linked by carbonyl
MADE in the liver and dumped into blood. No transporter needed.
Will not change pH, not charged. Polar so will go through membrane.
What happens to nitrogen in most cells?
NH3 + glutamate > glutamine > kidney
enzyme is glutamine synthatase
What happens to glutamine in the kidney?
Glutaminase: Glutamine > glutamate + NH3
ammonium excreted in tubules
NH3 is a minor amount of excreted N
How do we carry ammonium in the blood?
Always as glutamine
Because it’s non polar and doesn’t change pH
Who is intestine tied into ammonia pathway?
Glutamine > intestine
Glutaminase: Glutamine > glutamate + NH3
NH3 (also from bacterial NH3) > hepatic portal vein > liver
When does muscle use AA and what happens to it?
During starvation.
AA > NH3 > NH3 + a keto glutarate > glutamate > NH3 + pyruvate > alanine > blood (not change pH)
Muscles also have transaminase (pyridoxal P)
Transaminase remove amino from AA
alanine aminotransaminase: takes amino group from glutamate puts it on pyruvate > alanine
What is alanine used for? coming from muscle
Alanine > liver > glutamate + pyruvate > glutamate > urea cycle
a-ketogluatarate: helps convert alanine to glutamate
Where does urea cycle begin?
Liver mitochondria
Urea cycle
Carbamoyl phosphatate synthetase I: NH4+ + HCO3- + 2 ATP > carbamoyl phosphotate
—- N acetyl glutamate and high protein activate it.
Orthinine Transcarbomoylase:
carbamoyl phosphate > citrulline
BUN
Blood Urea Nitrogen
Decreased BUN = liver dysfunction
— either OT or CPS I might not be working correct
Increased BUN= Kidney dysfunction
how is ammonium transported in the blood?
from muscle: alanine
usually: glutamine
What other enzymes can be used to determine liver function?
Alanine transaminase
Aspartate transaminase
Carbamoyl phosphate synthetase I defect
Hereditary, autosomal recessive
Inability for ammonia to be metabolized via urea cycle
No orotic aiduria hyperammonemia Blood glutamine increase BUN decreased Cerebral edema Lethargy convulsions, coma death
Ornithine transcarbamoylase
Hereditary, X lined recessive
Orotic aciduria and increase uracil (gout) hyperammonemia Blood glutamine increase BUN decreased Cerebral edema Lethargy convulsions, coma death
Enzyme deficiencies in urea cycle
Complete loss = death shortly after birth
Leads to:
Hyperammonemia
Build up of glutamin and glutamate
–brain swelling and neuro problems
Treated by dietary restriction in proteins
What is the key regulating enzyme in urea synthesis?
Carbamoyl phosphate synthetase I:
activated by n acetyl glutamate (NAG)
What does the urea cycle accomplish for the body?
Urea synthesis provides an efficient mechanism for land animals to remove excess nitrogen from the body. Urea is synthesized in the liver and exported to the kidneys where it enters the bladder.
Argininosuccinase deficiency
Inhibits flux through the urea cycle and causes hyperammonemia and neurological symptoms
Treated with a low protein diet that is supplemented with arginine, thereby resulting in argininosuccinate excretion a substitute for urea.
