1 / 10

Phenylketonuria (PKU)

Fourier Transform Ion Cyclotron Resonance (FT-ICR) Mass Spectrometry & Phenylketonuria (PKU) Screening. Phenylketonuria (PKU). Genetic d isorder characterized by the inability to metabolize phenylalanine, an essential amino acid Recessively inherited

aliza
Download Presentation

Phenylketonuria (PKU)

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Fourier Transform Ion Cyclotron Resonance (FT-ICR) Mass Spectrometry &Phenylketonuria (PKU) Screening

  2. Phenylketonuria (PKU) • Genetic disorder characterized by the inability to metabolize phenylalanine, an essential amino acid • Recessively inherited • Caused by partial or complete deficiency of phenylalanine hydroxylase • Enzyme that metabolizes phenylalanine into tyrosine • Accumulation of phenylalanine leads to neurological damage • Mental retardation, seizures Phenylalanine

  3. Phenylketonuria (PKU) • Treatment: Diet low in phenylalanine • Avoid high protein foods (meat, fish, poultry, eggs, cheese, milk, dried beans, peas) • Testing: Every state requires blood screening for all newborns • Fourier transform mass spectrometry often used • A high phenylalanine: tyrosine ratio (above 2:1) results in a positive screening

  4. Mass Spectrometry • Ion Source • Compound vaporized into gas phase • Energy added to ionize the compound • Excess energy may also fragment compound • Mass Analyzer • Fragments sorted based on mass/charge ratios (m/z) • Ions detected • Ion cyclotron resonance (ICR) in an ion trap is a type of mass analyzer

  5. Fourier Transform-Ion Cyclotron Resonance (FT-ICR) Mass Spectrometry • Ions are trapped in an ion trap • Magnetic and electric fields used to make ions cycle • Ions excited by energy • Causes ions to move in packets • Ions perpendicular to a magnetic field move in a circular path with a radius & frequency: • Can measure cyclotron frequency and calculate the mass very accurately r = mv/eB f = eB/pm

  6. When ions pass by receiver plate, causes electrical signal called an image current • Signal is free induction decay • Consists of many superimposed sine waves • Fourier Transform converts time signal to frequencydomain, where mass can be calculated.

  7. Phenylalanine Fragmentation

  8. Mass Spectrum of L-Phenylalanine

  9. Advantages & Disadvantages Advantages • Extremely High Resolution (>500,000) • Very Good Accuracy (<1 ppm) Disadvantages • Expensive • Requires Superconducting Magnet

  10. GC FT-MS chromatographs of a PKU newborn before treatment (above) with a phenylalanine: tyrosine ratio of 2.30 and after three months of treatment (below) with a ratio of 1.02

More Related