AA Catabolism & Urea Cycle Flashcards
What are the 4 processes that AAs are used for?
- Protein synthesis
- Glucose synthesis
- Ketogenesis
- Synthesis of nitrogen-containing compounds
What are the two components that make up AAs and what is the fate of each?
- NH3 group: excreted as urea or NH4+ into urine
- Carbon skeleton (used in TCA Cycle or Gluconeogenesis)
What are the 3 groups by which AAs are classified?
- Glucogenic: AAs enter TCA Cycle and lead to increase of OAA which is used for gluconeogenesis
- Ketogenic: AAs form Acetyl CoA or Acetoacetate
- Glucogenic/Ketogenic: AAs used for either gluconeogenesis or ketogenesis
With Ketogenic AAs, why can’t the Acetyl CoA be used to make glucose?
The 2 Cs from Acetyl CoA are lost to CO2
Where are AAs catabolized?
LIVER ONLY
What is a transamination reaction? What type of enzymes are used for these reactions?
Transamination is the removal of NH3 from AAs to produce the carbon skeleton of AAs (alpha-ketoacids)
- Uses Aminotransferase enzymes (transaminases)
What are the two starting substrates and two end products of every transamination reaction? What accepts the NH3 from the AA?
- Alpha-Ketoglutarate accepts the NH3 to produce Glutamate
- AAs produce the carbon skeleton (alpha-ketoacids)
In what part of the body do non-branched chain AAs undergo transamination? In what part of the body do branched chain AAs undergo transamination?
- Non-branched chain AAs: transamination in liver
- Branched chain AAs: transamination in muscle
AAs arriving to the liver carry nitrogens from what two sources? Are these AAs arriving to the liver branched chain or non-branched chain AAs?
AAs arriving to the liver carry nitrogen from:
- Dietary AAs
- AAs broken down by muscle in fasting state
These AAs are non-branched chain
Why can’t BCAAs be metabolized by the liver? Where are BCAAs metabolized?
Liver lacks the enzymes (aminotransferases) to deaminate BCAAs
BCAAs are metabolized in muscle
What are the three AAs metabolized in muscle? (hint: branched chain AAs)
- Valine
- Isoleucine
- Leucine
What is the fate of muscle AAs? Describe the process.
- BCAAs are deaminated (NH3+ removed) and sent to the muscle where they are metabolized
- The nitrogen is given to Glutamate
- The nitrogen is then added to either Alanine or Glutamine and enters circulation
What happens to Alanine after it is produced in the muscle? What happens to Glutamine after it is produced in the muscle?
They are sent into circulation and taken up by:
- Alanine: taken up by liver and metabolized like non-branched-chain AAs
- Glutamine: taken up by kidneys and serves as an alternative nitrogen excretion mechanism (as NH4+)
What is the Glucose Alanine Cycle?
Allows for the transfer of BCAA amino nitrogens from the muscle to liver
What is the first step of the Glucose Alanine Cycle? What is the enzyme used in this step?
Glutamate + Pyruvate > Alanine + alpha-ketoglutarate
- via MUSCLE Alanine Aminotransferase (ALT)
What is the second step of the Glucose Alanine Cycle? What is the enzyme used in this step?
Glutamate + Pyruvate > Alanine + alpha-ketoglutarate
- via LIVER Alanine Aminotransferase (ALT)
What is the fate of the Glutamate produced in the Glucose Alanine Cycle?
What is the fate of the Pyruvate produced in the Glucose Alanine Cycle?
- Glutamate is used as a key intermediate in nitrogen disposal pathway (urea or glutamine)
- Pyruvate is used in gluconeogenesis
What are the two ways by which glutamate delivers nitrogen to the Urea Cycle? What is the enzyme used for each process?
- Amino group from glutamate is deaminated to produce NH3 (then protonated to NH4+): Glutamate > NH3 + alpha-ketoglutarate
- uses Glutamate Dehydrogenase - Amino group from Glutamate incorporated into Aspartate: Glutamate + OAA > Aspartate + alpha-ketoglutarate
- uses Aspartate Aminotransferase
What are the sources of the two nitrogens found on urea in the Urea Cycle? (hint: come from glutamate)
- NH4+ via reaction by Glutamate Dehydrogenase
2. Aspartate via reaction by Aspartate Aminotransferase
What is the function of the Urea Cycle and where does it occur?
Urea Cycle disposes of nitrogen in a non-toxic form (urea) and transports it to the kidneys where it is excreted as urine
- Occurs in the liver
What is the energy requirement of the Urea Cycle and where does this energy come from?
ATP is required - this ATP comes from B-oxidation
What is the rate limiting enzyme of Urea Cycle? How is this enzyme regulated?
CPSI (Carbamoyl Phosphate Synthetase I)
- Activated by high glutamate in the liver (need for nitrogen disposal)
+ N-acetylglutamate
- Acidosis (protons)
What are the three fates of the Glutamate produced from AAs (either from muscle or diet)?
- Glutamate + OAA > Aspartate + alpha-ketoglutarate (via Aspartate Aminotransferase)
- Glutamate > NH3 + alpha-ketoglutarate (via Glutamate Dehydrogenase)
- Glutamate + NH4+ > Glutamine (via Glutamine Synthetase)
When additional NH4+ is needed to produce glutamine, which enzyme is utilized? Where is this enzyme found in the body?
Glutamate Dehydrogenase
- Found in liver and muscle
