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Related Experiment Videos

Alkyl-dihydroxyacetonephosphate synthase.

E C de Vet1, H van den Bosch

  • 1Department of Biochemistry of Lipids, Centre for Biomembranes and Lipid Enzymology, Institute for Biomembranes, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands. e.c.jm.devet@chem.uu.nl

Cell Biochemistry and Biophysics
|May 2, 2001
PubMed
Summary

Researchers identified the enzyme alkyl-dihydroxyacetonephosphate synthase, crucial for ether phospholipid biosynthesis. They cloned human and guinea pig genes, revealing a precursor protein with a peroxisomal targeting signal (PTS) type 2.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Ether phospholipids are vital components of cell membranes, and their biosynthesis initiates in peroxisomes.
  • Alkyl-dihydroxyacetonephosphate synthase (ADFPS) is the key peroxisomal enzyme responsible for introducing the ether linkage during this process.

Purpose of the Study:

  • To clone and characterize the cDNAs encoding ADFPS from mammalian (guinea pig and human) and invertebrate (Caenorhabditis elegans) sources.
  • To investigate the molecular basis of ADFPS deficiency in human genetic disorders.

Main Methods:

  • Purification of ADFPS from guinea pig liver.
  • Amino acid sequencing of purified ADFPS.
  • Cloning of ADFPS cDNAs using obtained sequences.
  • Analysis of ADFPS precursor protein processing and targeting signals.

Related Experiment Videos

  • Examination of ADFPS levels in patient-derived fibroblasts.

    • Main Results:

    • ADFPS was purified, and its cDNAs were cloned from guinea pig and human liver.
    • Mammalian ADFPS is synthesized as a precursor with a N-terminal peroxisomal targeting signal (PTS) type 2.
    • Reduced ADFPS levels were observed in fibroblasts from Zellweger syndrome and rhizomelic chondrodysplasia punctata patients, indicating a role in these disorders.
    • A C. elegans homolog of ADFPS was identified, lacking the N-terminal PTS type 2 but possessing a C-terminal PTS type 1.

    Conclusions:

    • The study elucidates the molecular cloning and characterization of ADFPS, a critical enzyme in ether phospholipid biosynthesis.
    • It identifies a specific molecular defect in certain human peroxisomal disorders and highlights differences in peroxisomal targeting signals between mammalian and C. elegans ADFPS.