BIOC Lecture 7: Nitrogen II Flashcards
When does amino acid catabolism occur?
- Excess protein is consumed
- Insufficient dietary protein
- Insufficient dietary energy
What happens in the situations where amino acid catabolism occurs?
Carbon skeletons enter the main energy pathways and amino groups are processed to urea in the liver for excretion
What do aminotransferase enzymes catalyse?
Transaminase reactions to transfer amines
What are aminotransferase enzymes sometimes called?
Transaminases
How do aminotransferases work?
- Generate a keto acid from original AA
- Pyridoxamine phosphate is now in N bound form
- It then transfers N to another keto acid
- New AA is formed
How do we make new AA’s?
An interchanging of N groups to other keto acids
What organ has the highest concentration of aminotransferase enzymes?
Liver
The receiving keto acid (the one that picks up the nitrogen) is generally one of what three keto acids?
- α-Ketoglutarate
- Oxaloacetate
- Pyruvate
Where is Pyridoxamine phosphate derived from?
Vitamin B6
Where is Pyridoxamine phosphate found?
In the active center of the transaminase enzyme
What is the amino acid - keto acid pair for a-ketoglutarate?
Glutamate
What is the amino acid - keto acid pair for oxaloacetate?
Aspartate
What is the amino acid - keto acid pair for pyruvate?
Alanine
The deamination of most amino acids leads to the production of what?
Glutamate, aspartate or alanine
What AA is produced the most?
Glutamate as a-ketoglutarate is the most prominent
Aminotransferases are specific for the donor amino acid but mostly only accept?
a-ketoglutarate or oxaloacetate as the donor keto acid
Are aminotransferases reactions reversible?
Yes - dependent on concentration of substrates
What do aminotransferases require?
the co-enzyme pyridoxal-phosphate (derived from the vitamin B6) which is involved in transfer of the amino group
What do aminotransferases allow for?
Generation of AA’s in short supply and safe removal of excess amino groups
What can glutamate form?
Glutamine
What is the glutamate-glutamine reaction catalysed by?
Glutamine synthetase (GS)
What are glutamate and glutamine very important in?
Brining the nitrogen back from tissues
Why is glutamine special?
Because it can carry two amine groups, therefore is very efficient in terms of transferring nitrogen
How does the reaction of glutamate become glutamine?
- Catalysed by GS
- Fixes another ammonia group onto glutamate structure
- Requires ATP
When is the glutamate-glutamine reaction highly driven?
When there is high levels of ammonia - you don’t want free ammonia in the tissues
What is the reaction that converts glutamine back to glutamate catalyzed by?
Glutaminase
What happens in the reaction from glutamine to glutamate?
- Glutamine loses an amino group
- Release of ammonia
- Ammonia is then used to make urea in the liver
What is the loss of an amino group called?
Oxidative deamination
What is the reaction of glutamate losing its amino group catalyzed by?
Glutamate dehydrogenase (GDH)
Glutamate dehydrogenase is one of very few enzymes that can use…
NAD or NADP
What ways can an amino group be removed?
- Transaminations
- Oxidative deamination
- Hydrolysis
What is hydrolysis?
a molecule is split into two parts by the addition of a water molecule
What is oxidative deamination?
the removal of an amino group from an amino acid, producing a keto acid and free ammonia
Where are glutamine and alanine prominent?
In plasma
How is Nitrogen transported in most tissues?
Most tissues in terms of nitrogen metabolism, the nitrogen for transfer to the liver will be contained in glutamate
- The glutamine synthetase reaction will occur to give you glutamine
What happens to glutamine after it is produced in most tissues?
It will then go back to the liver
What happens to glutamine in the liver?
- It will undergo the glutaminase reaction which will release one ammonia group
- Glutamate can also then undergo the glutamate dehydrogenase reaction to release its second ammonia
- That ammonia will be used to make urea
What is the glucose-alanine cycle?
a metabolic pathway that facilitates the exchange of metabolites between muscle and liver
What does the glucose-alanine cycle allow?
The muscles to transfer the amino group from amino acid catabolism to the liver, where it can be safely converted into urea and excreted
What is the main amino acid coming out of muscle?
Alanine
Why does lots of alanine come out of the muscle?
Skeletal muscle relies a lot on glycolysis for energy, there is high levels of pyruvate being formed, therefore high levels of alanine being produced
What happens in the muscle during the glucose-alanine cycle?
- Amino acids undergo transamination to form glutamate
- Glutamate donates its amino group to pyruvate forming alanine
- Alanine is then transported to the liver
What happens when alanine is transported to the liver?
- Alanine undergoes transamination again to form glutamate and pyruvate.
- Glutamate can then undergo oxidative deamination, releasing ammonia (NH₃) and regenerating α-ketoglutarate
- ammonia is converted to urea and excreted
What happens to the pyruvate generated by alanine in the glucose-alanine cycle?
used to synthesize glucose through gluconeogenesis.
