A m I n o c d S M E T B O L 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

Phenylalanine *Can not be synthesized in the body. m I n o c d S M E T B O L 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%

A m I n o c d S M E T B O L Phenylalanine

A m I n o c d S M E T B O L Major pathway Tyrosine Phenylalanine

Phenylalanine This reaction need O2 and at the m I n o c d S M E T B O L Phenylalanine This reaction need O2 and at the same time need a cofactor (molecule of tetrahydrobiopterine which is converted to dihydrobiopterine by the effect of biopterine reductase enzyme which need molecule of NADH to convert back to tetrahydrobiopterine

m I n o c d S M E α- T B O L A phenylpyruvate Phenylalanine phenyl acetate phenylaetylglutamine Phenyl lactate

Inborn Error of Metabolism Of Phenylalanine c d S M E T B O L Phenylketonuria: Deficiency of Ph. Hydroxylase enzyme *autosomal recessive 1/10000. *Treatable disease with 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:Dihydrobiopterine reductase enzyme. Hyperphenylalaninemia IV,V Defect: Synthesis of biopterine cofactor

Phenylketonuria (PKU) m I n o c d S M E T B O L Phenylketonuria (PKU) A disorder of the metabolism of phenylalanine, a substance present in milk and also in products containing aspartame (NutraSweet). 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.

PHENYLALANINE HYDROXYLASE m I n o c d S M E T B O L The normal metabolism of phenylalanine (pathways a and b) Dietry sources, particularly plant proteins BREAKDOWN PHENYLALANINE HYDROXYLASE PHENYLALANINE TYROSINE (b) (a) BODY PROTEINS © 2008 Paul Billiet ODWS

PHENYLALANINE HYDROXYLASE m I n o c d S M E T B O L The abnormal metabolism in phenylketonuric (pathway c) subjects HYDROXYPHENYLACETIC ACID Hydroxyphenylacetic Acid (c) PHENYLALANINE* Dietry sources, particularly plant proteins BODY PROTEINS (b) (a) PHENYLALANINE HYDROXYLASE (c) PHENYLACETIC ACID* *Agents, thought to be responsible for mental retardation © 2008 Paul Billiet ODWS

Phenylketonuria (PKU) m I n o c d S M E T B O L Phenylketonuria (PKU) The PKU gene is found on the chromosome 12, locus 24.1 in the phenylalanine hydroxylase gene

G g GG Gg gg Punnett Square Carriers of Phenylketonuria. Both Gg. m I n o c d S M E T B O L Punnett Square The punnet square below shows the results of when two parents, both carriers of PKU produce offspring. G g GG Gg gg Carriers of Phenylketonuria. Both Gg.

Phenylketonuria (PKU) m I n o c d S M E T B O L Phenylketonuria (PKU) 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) .

Biochemical Effects m I n o c d S M E T B O L A Accumulation of substrate of blocked reaction. Phenylalanine Reduced formation of the product . Tyrosine Alternative pathways of metabolism of the precursor,( formation & excretion of phenylpyruvate, phenyllactate & phenylacetate). The mental retardation of PKU can be prevented by a diet containing low level of phenylalanine up to six year

Phenylketonuria (PKU) m I n o c d S M E T B O L Phenylketonuria (PKU) 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. Screenig should be done after this time to avoid false negative. Positive rsult by quantitatve measurement of phenylalanine.

Phenylketonuria (PKU) m I n o c d S M E T B O L Phenylketonuria (PKU) Diagnosis:Measurement of phenylalanine in blood taken from a heel prick. Amino Acid Analysis High peak level of Phenylalanine and Low level of Tyrosine. Guthrie Test: Ferric Chloride Test: Urine Chromatography.

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. d S M E T B O L 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……

Supplementation with tyrosine. c d S M E T B O L Management: To lower plasma phenylalanine ,give low phenylalanine diet special milk formula). Supplementation with tyrosine. Diet may be terminated at age of 6 years. The earlier treatment is started ,the more completely neurological damage can be prevented Tyrosine can not be synthesized from phenylalanine and it becomes an essential amio acid and should be supplied in the diet.

A m I n o c d S M E T B O L PKU Treatment Meat, fish, eggs, cheese, milk products,, and bread are all foods that have high levels of phenylalanine