Phenylketonuria (PKU) is a metabolic genetic disorder caused by mutations in the PAH gene, which encodes the hepatic enzyme phenylalanine hydroxylase. This enzyme is necessary to metabolize the amino acid phenylalanine into tyrosine. Without this enzyme functioning properly, phenylalanine is not broken down and builds up in the blood, which can lead to intellectual disability if not treated through dietary restrictions. The document includes a metabolic flowchart illustrating the pathway of phenylalanine breakdown and how it is disrupted in PKU due to the deficient phenylalanine hydroxylase enzyme.

1. Phenylketonuria
a metabolic flowchart
Kristine Joy Y. Sumanga
MD-II CPU-ColMed

2. What is Phenylketonuria (PKU)?
an autosomal recessive metabolic genetic
disorder characterized by homozygous or compound
heterozygous mutations in the gene for the hepatic
enzyme phenylalanine hydroxylase (PAH), rendering it
nonfunctional.[ This enzyme is necessary to
metabolize the amino acid phenylalanine (Phe) to the
amino acid tyrosine (Tyr).

3. Precursor A
Substrate B
Toxic by-product
Product C
2 Deficient Enzyme
D E
General Metabolic Concept

4. Dietary Proteins
PhenylalaninePhenylpyruvic
acid
Tyrosine
Phenylalanine
Hydroxylase
3, 4
dihydroxyphenyl
alanine (DOPA)
Melanin pigments

5. The whole metabolic
pathway of PKU

6. Phenylalanine
Tyrosine
p-hydroxyphenylpyruvic acid
Homogentisic acid
2,5 dihydroxyphenylacetic acid
Maleylacetoacetic acid
Triiothyronine (T3)
Thyroxine (T4)
Glutamine GABA
Pyruvate Oxaloacetate
Glutamate decarboxylase
Pyruvate carboxylase
Phenylpyruvic acid
Phenylalanine
hydrolase
Tyrosine
transaminase
p-hydroxyphenylpyruvic
acid oxidase
Homogentisic acid
oxidase
Fumanylacetoacetic acid
Fumaric acid Acetoacetic acid
Carbon dioxide + Water
Iodinase 3,4 dihydroxyphenylalanine (DOPA) Melanin
Pigments
(decrease
pigmentation,
Blue eyes)
(Cretinisim)
(increased mousy odor)
(seizure ,increase deep
tendon reflex)
(decrease ATP, mental retardation)
(-)BH4
X
X
X
X

7. Thank You and God bless