Download PHENYLKETONURIA

PHENYLKETONURIA
Stephanie Holton
Phenylketonuria
Genotype:
• Mutuation of the enzyme, phenylalanine
hydroxylase (PAH)
Phenotype:
• Mental Retardation, Seizures, Fair Skin,
“Mousy Odor” & Eczema.
Phenylketonuria
PAH Gene• Location: chromosome 12q22-24
• Length: 79,278 bp’s (13 exons)
• Over 450 mutations in the gene have been
identified in patients with PKU.
Phenylketonuria
Normal PAH gene function• Responsible for the first step in processing
the amino acid phenylalanine.
• Also, necessary for the conversion of
phenylalanine to tyrosine.
Phenylketonuria
Phenylketonuria
Conserved Domains1) ACT: (35-109) regulatory role
2) euPHeOH: (119-424)
• Catalyzes the first and rate-limiting step in
the metabolism of phenylalanine
• Location of PAH mutation in PKU
Phenylketonuria
PAH Mutation• Most common is located at position 408
• A substitution of an Arginine with a
Tryptophan(Arg408Trp).
Phenylketonuria
Aberrant Function• Reduces the activity of phenylalanine
hydroxylase
• Phenylalanine ingested in foods cannot be
metabolized and accumulates to toxic levels
in the bloodstream and other tissues
Phenylketonuria
Aberrant Phenotype• The increased levels of Phenylalanine can
cause brain damage, if left untreated.
• Tyrosine- necessary for production of certain
neurotransmitters & melanin (in hair in skin)
References
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cg
i?id=261600
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?d
b=gene&cmd=Retrieve&dopt=full_report&list
_uids=5053
http://ghr.nlm.nih.gov/gene=pah