Biochemistry- amino acid catabolism

Question 1

Can all amino acids be fully oxidised in the TCA cycle?

Answer 1

Yes, although they enter it in different ways.

Question 2

Which amino acids are degraded?

Answer 2

Those which are not needed as building blocks for biosynthetic reactions, as they cannot be stored.

Question 3

What is the major site of amino acid degradation?

Answer 3

The liver

Question 4

Where do the amino acids come from that are degraded?

Answer 4

1. Our diet
2. Protein turnover: protein may be broken down in regulation of protein turnover and damaged proteins may need to be broken down.

Question 5

Why can nitrogen in the amino acids be problematic?

Answer 5

Because ammonium is toxic at high concentrations, and a build up can lead to severe problems.
Therefore we need a safe way of excreting nitrogen.

Question 6

What are the nitrogen-containing excretory molecules?

Answer 6

Urea (the vast majority)
Uric acid
Creatinine
Ammonium ion

Question 7

How many steps are in the urea cycle?

Answer 7

3

Question 8

Describe the synthesis of urea.

Answer 8

Step 1: Can occur in all tissues
The amino acid of an amino acid is transferred onto a keto acid, usually alpha ketoglutarate, which is a TCA intermediate.
This is called transamination.
Transamination forms a new keto acid and a new amino acid.
If ketoglutarate is the keto acid taking part in the transamination reaction, the product is glutamic acid. Since the second step occurs in the liver, the amino acids have to be transported to the liver. The amino group is either transferred to pyruvate in a transamination reaction to form alanine, or glutamine synthase uses glutamate and a free ammonium ion to form glutamine. These are the major carriers of nitrogen in the blood to the liver.
Step 2: Occurs in the liver.
The amino acid is removed from glutamic acid (this is deamination), which forms alpha ketoglutarate again, and this amino acid group is converted to a free ammonium ion.
Step 3: The free ammonium ions enters the urea/ornithine cycle. One carbon dioxide, one free ammonium ion, one aspartate molecule (containing the second nitrogen), 3 ATP and 2 H20 go into the urea cycle, and the products are urea, 2 ADP + Pi and 1 AMP + Pi and fumarate.
It is an energy consuming reaction.

Question 9

What happens to the carbon skeletons once the amino groups have been removed from the amino acids?

Answer 9

They are converted into major metabolic intermediates.
They can be converted to glucose in gluconeogenesis or oxidised in the TCA cycle.
Ketogenic amino acids:
are degraded to acetyl-coA or acetoacetyl-coA
These can enter the TCA cycle, give rise to ketone bodies or fatty acids.
Glucogenic amino acids:
are degraded to pyruvate or TCA cycle intermediates
These can be converted to phosphoenolpyruvate and then into glucose in gluconeogenesis.

Question 10

Name and describe 3 inherited disorders associated with amino acid degradation

Answer 10

Alcaptonuria: the degradation of tyrosine and phenylalanine is blocked.
Maple syrup urine disease: degradation of valine, isoleucine and leucine is blocked
The patient’s urine smells like maple syrup
The results are mental and physical retardation, but these can be prevented by an appropriate diet
Phenylketonuria: Phenylalanine accumulates in all the body fluids
It leads to severe mental retardation if untreated
Can be treated with a low phenylalanine diet