Amino Acid Catabolism

Question 1

Why are all amino acids that are not used degraded?

Answer 1

No storage form for amino acids.

Question 2

What is the main site of amino acid degradation?

Answer 2

The liver.

Question 3

What is produced from amino acid breakdown?

Answer 3

Ammonia (NH3) and ammonium ions (NH4+).

Question 4

Why do we need a safe way of excreting these?

Answer 4

Build up of these leads to severe problems.

Question 5

What are the major nitrogen-containing excretory molecules?

Answer 5

Urea: 80%, formed in liver (not kidneys), 25-30g/24 hours.
Others: uric acids, creatinine and ammonium ions.

Question 6

Name the 3 steps for the synthesis of urea?

Answer 6

1. Transamination.
2. Deamination.
3. Urea (or ornithine) cycle.

Question 7

What are the enzymes involved in transamination and what do they do?

Answer 7

Aminotransferases. They move the amino group from alpha-amino acids to alpha-keto acids.

Question 8

What is the usual keto acid in transamination and what does this produce?

Answer 8

Alpha-ketoglutarate (TCA intermediate). Gives glutamate.

Question 9

What tissues does transamination occur in?

Answer 9

All tissues.

Question 10

How is glutamate prepared for transport to the liver?

Answer 10

Amino group of glutamate is transferred to pyruvate, giving alanine.
OR
Glutamine synthase adds NH4+ to glutamate giving glutamine.

Question 11

Where does deamination and the urea cycle occur?

Answer 11

In the liver.

Question 12

Describe deamination.

Answer 12

Removal of amino group from glutamic acid. Results in formation of alpha-ketoglutarate. NAD+ + H+ accepts an electron and an ammonium ion is formed.

Question 13

Describe the urea (or ornithine) cycle.

Answer 13

Ammonium ion converted to urea by addition of aspartic acid (another amino acid).

Question 14

Where are the 2 nitrogens of urea derived from?

Answer 14

1 from aspartic acid, the other from the free ammonium ion.

Question 15

Where does the extra carbon in urea come from?

Answer 15

CO2.

Question 16

How much energy does the urea cycle cost?

Answer 16

3 ATP (4 phosphate bonds are broken as 2 ADP and 1 AMP is formed).

Question 17

What is another product of the urea cycle and what is its function?

Answer 17

Fumarate (intermediate of the TCA cycle).

Question 18

What happens to the remaining carbon skeletons of ketogenic amino acids?

Answer 18

Degraded to acetyl-CoA or acetoacetyl-CoA.

Can give rise to ketone bodies or fatty acids.

Question 19

What happens to the remaining carbon skeletons of glucogenic amino acids?

Answer 19

Degraded to pyruvate or TCA cycle intermediates.

Can be converted into phosphoenolpyruvate and then into glucose.

Question 20

What are the causes of alcaptonuria, maple syrup urine disease and phenylketonuria.

Answer 20

Degradation of certain amino acids are blocked.

Question 21

What are the effects and treatment of maple syrup urine disease?

Answer 21

Mental and physical retardation. Prevented by appropriate diet.

Question 22

What are the effects and treatment of phenylketonuria?

Answer 22

Severe mental retardation.

Therapy is low phenylalanine diet.

Question 23

Describe the sequence of events when there is a defect in a urea cycle enzyme.

Answer 23

Accumulation of urea cycle intermediates. Glutamine levels increase in the circulation. Alpha-ketoglutarate is no longer recommended. Alpha-ketoglutarate levels become too low to fix more free ammonium ions. Levels of ammonia in the blood are elevated.

Question 24

How would you treat a urea cycle disorder?

Answer 24

Low-protein diet, drugs which remove nitrogen e.g. forming complexes with amino acids which are excreted, gene therapies in hepatocytes.