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 Conserved Domains- 1) 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.cgi?id=261600 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uids=5053 http://ghr.nlm.nih.gov/gene=pah