Urea Cycle Defects and Ammonia

Question 1

Genetic disorders and mutation can cause the complete lack and/or the partial loss of an enzyme in the urea cycle. What can this lead to? (2)

Answer 1

Hyperammonaemia

Accumulation/excretion of urea cycle intermediates

Question 2

What are the symptoms of a defect in the urea cycle?

Answer 2

Vomiting 
Lethargy
Irritability
Mental retardation
Seizures
Coma

Question 3

How are defects in the urea cycle managed?

Answer 3

Low protein diet

Replace amino acids in diet with keto acids (get rid of amine groups)

Question 4

What are the toxic effects of ammonia?

Answer 4

1. Interference with amino acid transport and protein synthesis
2. Disruption of cerebral blood flow
3. PH effects (alkaline)
4. Interference with metabolism of excitatory amino acid neurotransmitters (eg glutamate and aspartate)
5. Alteration of the blood-brain barrier
6. Interference with the TCA cycle (reacts with intermediate to form glutamate)