MMT: amino acid catabolism I Flashcards
How do we store amino acids?
We don’t
What are the major components of an amino acid?
An amino group and a carbon skeleton
How is the amino group removed from the body?
The urea cycle
What are the 3 key steps of removing an amino group?
Transamination, oxidative deamination, urea cycle
Describe transamination.
An amino group gets transferred from the amino acid to a-ketoglutarate (ALWAYS) to form glutamate via an aminotransferase
What cofactor is required during transamination?
PLP
PLP is derived from…
B6
Describe oxidative deamination.
NAD+ is used to remove the amino group from glutamate, forming NADH and ammonia. This molecule of ammonia can enter the urea cycle.
What enzyme is used in oxidative deamination?
Glutamate dehydrogenase
What happens to glutamate following oxidative deamination?
It is converted back to a-ketoglutarate, and can go on to accept more amino groups and continue its cycle
What would happen if we did lots of oxidative deamination in tissues other than the liver?
We’d get a huge buildup of ammonia, since really only the liver can do the urea cycle
What happens in the urea cycle?
Generation of urea from ammonia
What is reductive animation?
In extrahepatic tissues where the urea cycle can’t happen, we can fix ammonium to a-ketoglutarate to make glutamate to prevent buildup of ammonium
In what forms can ammonium be sent back to the liver?
As alanine or glutamine
Describe the alanine shuttle.
- Glutamate converts to alanine
- Alanine transports to the liver
- Alanine breaks into glutamate and pyruvate
- The glutamate can undergo the oxidative deamination to release ammonia, which can then undergo the urea cycle
- The pyruvate will become glucose and return back to tissues
Describe glutamine shuttle.
- Glutamate converts to glutamine, which is transported to the liver
- Glutamine breaks back into glutamate by releasing ammonia
- Glutamate is broken into a-ketoglutarate and ammonia
- Ammonia enters the urea cycle
How many ammonias are delivered by glutamate?
2
Where does the urea cycle occur?
The liver only
Where do the ammonia in urea molecules come from?
One from an amino acid breakdown and one from aspartate from the TCA cycle
What is the rate limiting enzyme of the urea cycle?
CPS I
Describe CPS I enzyme.
Catalyzes the first step in the urea cycle in the mitochondria using 2 ATP
What cofactor does CPS I need?
N-acetyl glutamate
What can N-acetylglutamate do?
Allosterically activate the urea cycle; it uses arginine, so high levels of arginine from an active urea cycle cause further activation of N-acetylglutamate and therefore CPS I
Describe ornithine transcarbamoylase.
Forms citrulline from ornithine and carbamoyl phosphate in the mitochondria, which then leaves and enters the cytoplasm
Describe arginosuccinate synthetase.
In the cytoplasm forms arginosuccinate from aspartate and citrulline
What does arginosuccinase do?
Breaks arginosuccinate to form arginine and fumarate that can be shunted into the TCA cycle
What does arginase do?
Convert arginine to ornithine and urea. The ornithine will re-enter the cycle to generate the second urea.
How much ATP do we need for one urea molecule?
4
