Phenylalanine Lecture Notes PDF

PHENYLALANINE phenylalanine (Phe), one of the essential amino acids that cannot be manufactured by the body and must therefore be consumed in protein rich foods Metabolism of Phenylalanine: *It is one of the essential Aromatic Amino Acid. *Can not be synthesized in the body. *It is metabolized mainl...

PHENYLALANINE phenylalanine (Phe), one of the essential amino acids that cannot be manufactured by the body and must therefore be consumed in protein rich foods Metabolism of Phenylalanine: *It is one of the essential Aromatic Amino Acid. *Can not be synthesized in the body. *It is metabolized mainly in the liver in to two pathway: 1.Major pathway (Hydroxylation pathway) Tyrosine pathway) 90% 2.Minor pathway (Transamination pathway) 10% This reaction need O2 and at the same time need a cofactor (molecule of tetrahydrobiopterin which is converted to dihydrobiopterin by the effect of biopterin reductase enzyme which need molecule of NADH to convert back to tetrahydrobiopterin Inborn Error of Metabolism Of Phenylalanine Phenylketonuria:Deficiency of Phe. Hydroxylase enzyme *autosomal recessive 1/10000. *Treatable disease when early diagnosis. Late diagnosis lead to mental retardation, if diagnose after 2 weeks Classification: Hyperphenylalaninemia I (classical) Defect: Phenylalanine hydroxylase. Hyperphenylalaninemia II ,III (minority) Defect: Dihydrobiopterin reductase enzyme. Hyperphenylalaninemia IV,V Defect: Synthesis of biopterin cofactor  The PKU gene is found on the chromosome 12, locus 24.1 in the phenylalanine hydroxylase gene A disorder of the metabolism of phenylalanine, a substance present in milk and also in products containing aspartame. Phenylalanine is not metabolized by the body it accumulates in the blood and reaches toxic levels, damaging various body structures, including the brain. PKU is largely preventable, and testing for PKU in newborns is required. Neonatal Screening Early diagnosis of PKU is important because the disease is treatable by diet. However the infant has normal blood level of phenylalanine at birth because the mother clears increased blood phenylalanine in her affected fetus through the placenta, Normal level of phenylalanine my persist until the new born is exposed to 24-48 hr protein feeding. Screening should be done after this time to avoid false negative. Positive result by quantitative measurement of phenylalanine. Diagnosis: Measurement of phenylalanine in blood taken from a heel prick. 1.Amino Acid Analysis High peak level of Phenylalanine and Low level of Tyrosine. 2.Guthrie Test: 3.Ferric Chloride Test: 4.Urine Chromatography. Clinical Features: **Irritability, feeding problem, vomiting. fits during the first week of life **Mental retardation developing between 4-6 months. **Generalized Eczema. **Tendency to reduce melanin formation because of reduced production of tyrosine. Blue eyes. ** Deficiency of pigmentation (fair hair, light skin colour). Amino Acid analysis in the blood is the most important method which give high peak of phenylalanine& low peak of Tyrosine. The advantage of this method is the early diagnosis. It is only suitable for mass screening. ** Should be performed about 4 days after birth. False positive……. Premature infant Ferric Chloride Test: Pink or green ring in urine …… Ferric chloride test for urine Management: 1. To lower plasma phenylalanine ,give low phenylalanine diet special milk formula). 2. Supplementation with tyrosine. 3. Diet may be terminated at age of 6 years. 4. The earlier treatment is started ,the more completely neurological damage can be prevented 5. Tyrosine can not be synthesized from phenylalanine and it becomes an essential amino acid and should be supplied in the diet. 6. Meat, fish, eggs, cheese, milk products, and bread are all foods that have high levels of phenylalanine