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Phenylketonur IA: Done by
Phenylketonur IA: Done by
IA
DONE BY :
BARAKATHU
PEER
FATHIMA
INDIA
Phenylketonuria (PKU) is an autosomal
recessive metabolic genetic disorder characterized
by a mutation 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. When PAH activity is
reduced, phenylalanine accumulates and is
converted into phenylpyruvate (also known as
phenylketone), which can be detected in the urine.
The enzyme phenylalanine
hydroxylase ( in the presence of
co-factor Tetrahydrobiopterin BH4)
normally converts the amino
acid phenylalanine into the amino
acid tyrosine. If this reaction
does not take place,
phenylalanine accumulates and
tyrosine is deficient. Excessive
phenylalanine can be metabolized
into phenylketones through the
with
minorglutamate. Metabolites
route, a transaminase
include
pathwayphenylacetate, phenylpyruvate
and phenethylamine. Elevated levels
of phenylalanine in the blood and
detection of phenylketones in the
urine is diagnostic, however most
patients are diagnosed via newborn
screening.
Phenylalanine is a large, neutral amino acid .
LNAAs compete for transport across the blood–
brain barrier via the large neutral amino acid
transporter . If phenylalanine is in excess in the
blood, it will saturate the transporter. Excessive
levels of phenylalanine tend to decrease the levels
of other LNAAs in the brain. However, as these
amino acids are necessary for protein and
neurotransmitter synthesis, Phe buildup hinders
the development of the brain, causing intellectual
disability.
THE NORMAL METABOLIs M OF
PHENYLALANINE ( PATHw AYs A AND B)
BREAKDOWN
Dietry
sources, PHENYLALANINE
particularly PHENYLALANINE HYDROXYLASE TYROSINE
plant (a)
proteins
(b)
BODY
PROTEINS
(c)
Dietry
sources, PHENYLALANINE
particularly HYDROXYLASE
PHENYLALANINE*
plant (a)
proteins
(c)
(b)
PHENYLACETIC BODY
ACID* PROTEINS
Newborn screening
allows early
identification and
early implementation
of treatment.
All babies are screened for PKU by heel-
prick test.
Blood tested for excess phenylalanine.
Blood placed on agar plate with bacteria
that need phenylalanine to grow.
Healthy babies’ blood doesn’t have extra
phenylalanine, so bacteria can’t grow.
Babies with PKU have extra
phenylalanine, so bacteria grow.
Bacterial plate with newborn
blood
sample
s Positive blood test results:
bacterial halo = PKU
Negative controls: no
bacterial growth
Positive controls : increasing
phenylalanine concentrations
give bacterial halos