Protein and Amino Acid Metabolism

Question 1

What enzyme is likely to be deficient in a patient with PKU?

Answer 1

Phenylalanine hydroxylase

Question 2

What pattern of inheritance does PKU show and which chromosome is the affected gene on?

Answer 2

Autosomal recessive, 12

Question 3

Which amino acid is deficient and thus needs to be supplemented in PKU?

Answer 3

Tyrosine

Question 4

What metabolic disorder are these symptoms of? Severe intellectual disability, developmental delay, microcephaly, seizures, hypopigmentation, musty smelling urine

Answer 4

Phenylketonuria

Question 5

What accumulates in the urine in PKU?

Answer 5

Phenylketones such as phenylacetate and phenyllactate

Question 6

How does PKU affect brain development?

Answer 6

Excess phenylalanine (a large neutral amino acid) can saturate the LNAA transporter across the blood-brain barrier, leading to decreased levels of other LNAAs and inhibiting protein and neurotransmitter synthesis

Question 7

What enzyme is most commonly defective in a patient with homocystinuria?

Answer 7

Cystathione beta-synthase

Question 8

What is the treatment for homocystinuria?

Answer 8

Low methionine diet and supplements of cysteine, B6, B12, Betaine and Folate

Question 9

What amino acid is present in the urine of a patient with homocystinuria and why?

Answer 9

Homocystine is present, which is the oxidised form of homocysteine which is synthesised from methionine and is in excess

Question 10

Why is homocystinuria often mistaken for Marfan’s syndrome and what is the difference?

Answer 10

They have similar clinical features such as lens dislocation and skeletal deformities. Excess homocysteine causes damage to collagen and elastic fibres by binding to lysine residues in proteins. Marfan’s is a genetic disorder of the connective tissue. There are no neurological effects present in Marfan’s