Amino Acid Catabolism Flashcards
Why are all amino acids that are not used degraded?
No storage form for amino acids.
What is the main site of amino acid degradation?
The liver.
What is produced from amino acid breakdown?
Ammonia (NH3) and ammonium ions (NH4+).
Why do we need a safe way of excreting these?
Build up of these leads to severe problems.
What are the major nitrogen-containing excretory molecules?
Urea: 80%, formed in liver (not kidneys), 25-30g/24 hours.
Others: uric acids, creatinine and ammonium ions.
Name the 3 steps for the synthesis of urea?
- Transamination.
- Deamination.
- Urea (or ornithine) cycle.
What are the enzymes involved in transamination and what do they do?
Aminotransferases. They move the amino group from alpha-amino acids to alpha-keto acids.
What is the usual keto acid in transamination and what does this produce?
Alpha-ketoglutarate (TCA intermediate). Gives glutamate.
What tissues does transamination occur in?
All tissues.
How is glutamate prepared for transport to the liver?
Amino group of glutamate is transferred to pyruvate, giving alanine.
OR
Glutamine synthase adds NH4+ to glutamate giving glutamine.
Where does deamination and the urea cycle occur?
In the liver.
Describe deamination.
Removal of amino group from glutamic acid. Results in formation of alpha-ketoglutarate. NAD+ + H+ accepts an electron and an ammonium ion is formed.
Describe the urea (or ornithine) cycle.
Ammonium ion converted to urea by addition of aspartic acid (another amino acid).
Where are the 2 nitrogens of urea derived from?
1 from aspartic acid, the other from the free ammonium ion.
Where does the extra carbon in urea come from?
CO2.
How much energy does the urea cycle cost?
3 ATP (4 phosphate bonds are broken as 2 ADP and 1 AMP is formed).
What is another product of the urea cycle and what is its function?
Fumarate (intermediate of the TCA cycle).
What happens to the remaining carbon skeletons of ketogenic amino acids?
Degraded to acetyl-CoA or acetoacetyl-CoA.
Can give rise to ketone bodies or fatty acids.
What happens to the remaining carbon skeletons of glucogenic amino acids?
Degraded to pyruvate or TCA cycle intermediates.
Can be converted into phosphoenolpyruvate and then into glucose.
What are the causes of alcaptonuria, maple syrup urine disease and phenylketonuria.
Degradation of certain amino acids are blocked.
What are the effects and treatment of maple syrup urine disease?
Mental and physical retardation. Prevented by appropriate diet.
What are the effects and treatment of phenylketonuria?
Severe mental retardation.
Therapy is low phenylalanine diet.
Describe the sequence of events when there is a defect in a urea cycle enzyme.
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.
How would you treat a urea cycle disorder?
Low-protein diet, drugs which remove nitrogen e.g. forming complexes with amino acids which are excreted, gene therapies in hepatocytes.
