phenylalanine is an essential, aromatic amino acid.

phenylalanine

1. PHENYLALANINE METABOLISM

2. PHENYLALANINE Phenylalanine is an essential, aromatic amino acid. Its is partly glucogenic and partly ketogenic. The need for phenylalanine becomes minimal, if adequate tyrosine is supplied in the food. This is called the sparing action of tyrosine on phenylalanine.

3. CATABOLISM OF PHENYLALANINE

4. IMPORTANT SPECIALIZED PRODUCTS FROM TYROSINE Melanin Catecholamines ( epinephrine, norepinephrine and dopamine) Thyroxine.

5. CATABOLISM OF TYROSINE AND PHENYLALANINE

6. INBORN ERRORS ASSOCIATED WITH PHENYLALANINE Phenylketonuria (OMIM: 261600) The deficiency of phenylalanine hydroxylase 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. It is a recessive condition. There are five types of PKU. Type 1: phenylalanine hydroxylase deficiency. Type 2 and 3: dihydrobiopterin reductase deficiency. Type 4 and 5: deficiency of the enzyme synthesizing biopterin .

7. Biochemical Abnormalities in PKU Phenylalanine cannot be converted to tyrosine. So, phenylalanine accumulates. Phenylalanine level in blood is elevated. So alternate pathways operate. Phenylketones , phenyllactate and phenylacetate are excreted in urine.

8. Clinical Manifestations in PKU The classical PKU child is mentally retarded with an IQ of 50. Agitation, hyperactivity, tremors and convulsions are often manifested. The child has hypopigmentation, explained by the decreased availability of tyrosine. Phenylacetic acid in sweat may lead to mousy body odor.

9. Laboratory Diagnosis Blood phenylalanine : Normal level is 1 mg/dl. In PKU, the level is >20 mg/dl. Tandem mass spectroscopy is the most reliable test; but is costly. Guthrie test is a rapid screening test. DNA probes are now available to diagnose the defects in phenylalanine hydroxylase and dihydrobiopterin deficiency. Ferric chloride test: Urine pf the patient contains phenylketones about 500-3,000 mg/day. This could be detected by adding a drop of ferric chloride to the urine. Transient blue-green color is positive test. It is a less reliable test.

10. Treatment Policy Early detection is very important. About 5 units of IQ are lost for each 10 week delay in starting the treatment. The treatment is to provide a diet containing low phenylalanine (10-20mg/kg body weight per day). Food based on tapioca will have low phenylalanine content.

11. Phenylketonuria carrier state Phenylketonuria is recessive; the disease is manifested only in homozygous state. In heterozygous (carrier) state, the phenylalanine hydroxylase enzyme is sufficient to metabolize normal levels of phenylalanine. But when phenylalanine (4g) injected intravenously, the carriers will show increased level in the blood. This is called phenylalanine load test.

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