Inborn error metabolism of amino acids

Inborn errors of amino acid metabolism are metabolic disorders of in which impair the synthesis and degradation .amino acids .
Abnormality in phenylalanine and Tyrosine metabolism
1- PHENYL KETONURIA (PKU)
Deficiency of phenyl alanine hydroxylase (Fig.17.1) is the cause for this disease. The genetic mutation may be such that either the enzyme is not synthesized, or a non-functional enzyme is synthesized.
Phenyketonuria (PKU) is a genetic disorder that is characterized by an inability of the body to metabolize phenylalanine, caused by a deficiency in Phenylalanine Hydroxylase (PAH) enzyme or The defect is due to deficiency of dihydrobiopterin reductase.an enzyme that catalyzes the regeneration of tetrahydrobiopterin (cofactor of PAH)




4. Biochemical Abnormalities
A. Phenylalanine could not be converted to tyrosine. So phenylalanine accumulates. Phenylalanine level in blood is elevated.
B. So alternate minor pathways are opened accumulation of too much phenylalanine and its toxic metabolities phenylpyruvic acid, phenyllactic acid and phenylacetic acid. which becomes a major donor of amino groups in aminotransferase activity and depletes neural tissue of ?-ketoglutarate. Absence of ?-ketoglutarate in the brain shuts down the TCA cycle and the associated production of aerobic energy, which is essential to normal brain development.
Phenyl ketone (phenyl pyruvate), phenyl lactate and phenyl acetate are excretedin urine.
Clinical Manifestations
A. The classical PKU child is mentally retarded
B. Agitation, hyperactivity, tremors and convulsions are often manifested. This may be because phenylalanineinterferes with neurotransmitter synthesis. Since tetrahydrobioptrerin is the co-enzyme
required for serotonin and dopamine, the decreased level of these neurotransmitters may also result in the neurological symptoms.
C. The child often has hypopigmentation, explained by the decreased level of tyrosine.
D. Phenyl lactic acid in sweat may lead to mousy body odor.