AA metabolism

Question 1

How are AA catabolised? (2 routes)

Answer 1

1. Transdeamination
   AA transaminated to a ketoacid and glutamate is formed.
   Glutamate can be deaminated in the mitochondria to release NH4+ and alpha-ketoglutarate.
2. Transamination
   Ketoacid transaminated to aspartate which can enter the urea cycle

Question 2

How is ammonia formed?

Answer 2

Protein turnover,
Inactivation of neurotransmitters,
Exercise
Protein breakdown

Question 3

Why is ammonia removed from the body?

Answer 3

It is toxic

Question 4

How is ammonia removed from the brain?

Answer 4

Alpha-ketoglutarate is converted to glutamate (using NADPH or NADH) by glutamate dehydrogenase - this uses an ammonium ion
Glutamate is converted to glutamine using glutamine synthase requiring an ammonium ion.
Ammonia is removed from the Brian as glutamine

Question 5

Why is it important that for each alpha-ketoglutarate 2 ammonium ions are removed in the brain?

Answer 5

It reduced the depletion of the important TCA cycle intermediate

Question 6

What happens to glutamine from the brain?

Answer 6

Glutamine is transported to the liver where it is converted to glutamate using glutaminase this releases an ammonium ion which enters the urea cycle.
Glutamate undergoes oxidative deamination and the 2nd ammonium ion is released and enters the urea cycle

Question 7

How is ammonia removed from the muscle?

Answer 7

Alpha-ketoglutarate is converted to glutamate using NADPH or NADH and NH4+ by glutamate dehydrogenase.
Glutamate is transaminated into alpha-ketoglutarate using pyruvate –> alanine (alanine aminotransferase). Alanine leaves the muscles and goes to the liver

Question 8

How do the muscles ensure that alpha-ketoglutarate is not depleted?

Answer 8

It is reformed from the transamination of glutamate

Question 9

Why do the muscles use pyruvate to remove ammonia?

Answer 9

Ammonia is formed through exercise.

Pyruvate increases during exercise.

Question 10

What happens when alanine reaches the liver?

Answer 10

It is transaminated back to glutamate.
Glutamate undergoes oxidative deamination and releases an NH4+ into the urea cycle.
Pyruvate enters gluconeogenesis

Question 11

What is the process of oxidative deamination, where does it occur?

Answer 11

In the liver mitochondria
Glutamate is converted to alpha-ketoglutarate by glutamate dehydrogenase.
This uses NAD+
NH4+ is released and enters urea cycle

Question 12

What is the purpose of the urea cycle?

Answer 12

Converts ammonia to urea in the liver

Question 13

What acts as the base for the urea cycle?

Answer 13

Ornithine

Question 14

How many ammonium ions are eliminated for each molecule fo urea produced?

Answer 14

2

Question 15

What is the fate of urea?

Answer 15

Travels in the blood to the kidneys and is excreted

Question 16

What is the rate limiting step of the urea cycle?

Answer 16

CO2 + NH4+ –> carbamoyl phosphate

This uses 2ATP and carbonyl phosphate synthase

Question 17

How do each NH4+ enter the urea cycle?

Answer 17

1. Through the rate limiting step to from carbamoyl phosphate.
2. As aspartate

Question 18

What enzyme converts arginine to ornithine releasing urea?

Answer 18

Arginase

Question 19

What increases the activity of carbamoyl phosphate synthase?

Answer 19

Increased deamination of AA via allosteric activators

Question 20

How is the aspartate that enters the urea cycle formed?

Answer 20

From the fumarate released in the urea cycle

Question 21

Where does the urea cycle take place?

Answer 21

Partly in liver mitochondria partly in cytosol