Week 9 Errors In Amino Acid Metabolism

Question 1

SOME HUMAN GENETIC DISORDERS AFFECTING AA CATABOLISM

Question 2

DEFECTS IN CATABOLISM OF PHENYLALANINE (AND TYROSINE)

Answer 2

Phenylketonuria (PKU)
If phenylalanine hydroxylase is non-functioning (as in PKU patients) catabolism proceeds by an alternative pathway.
Alkaptonuria
Build up of homogentisate turns urine black.
Can’t break down phenylalanine

Question 3

ALTERNATIVE PATHWAY OF PHENYLALANINE BREAKDOWN

Answer 3

Phenylalanine and phenylpyruvate accumulate in blood and tissues.
This impairs normal brain development.
Phenyllacetate gives urine a distinctive “mousy” odour, which was traditionally used to detect PKU in infants.
Babies are now routinely screened for PKU.
Patients are prescribed a diet low in phenylalanine.

Question 4

ARTIFICIAL SWEETENER ASPARTAME (E951) IS A SOURCE OF PHE

Question 5

NEW TREATMENT FOR PKU PATIENTS?

Question 6

BCAA’S ARE NOT DEGRADED IN THE LIVER

Answer 6

Leucine, isoleucine and valine are oxidised as fuel in brain, adipose tissue, muscle and kidney.
These tissues contain an aminotransferase absent in the liver
Defects in one of the enzyme complexes leads to MSUD.

Question 7

MAPLE SYRUP URINE DISEASE (MSUD)

Answer 7

MSUD patients have defective branched-chain α-keto acid dehydrogenase (BCKD) enzyme complex.

MSUD patients produce urine with a characteristic odour, due to build up of α-keto acids.

Rare disease resulting in abnormal brain development, mental retardation and death in early infancy.

Treatment involves careful control of diet: limit intake of Val, Iso and Leu.

Question 8

METHYLMALONIC ACIDAEMIA (MMA)

Answer 8

Patients with the rare genetic disease methylmalonic acidemia (MMA) lack functioning methylmalonyl-CoA mutase enzyme.
This leads to a build-up of a toxic intermediate – symptoms similar to poisoning with antifreeze.
Before this was discovered a woman was falsely imprisoned for poising her child!