Cellular and Molecular Life Sciences CMLS

, Volume 63, Issue 13, pp 1553–1563

Thiamine pyrophosphate: An essential cofactor for the α-oxidation in mammals – implications for thiamine deficiencies?

  • M. Sniekers
  • V. Foulon
  • G. P. Mannaerts
  • L. Van Maldergem
  • H. Mandel
  • B. D. Gelb
  • M. Casteels
  • P. P. Van Veldhoven
Research Article

DOI: 10.1007/s00018-005-5603-4

Cite this article as:
Sniekers, M., Foulon, V., Mannaerts, G.P. et al. Cell. Mol. Life Sci. (2006) 63: 1553. doi:10.1007/s00018-005-5603-4

Abstract.

The identification of 2-hydroxyphytanoyl-CoA lyase (2-HPCL), a thiamine pyrophosphate (TPP)-dependent peroxisomal enzyme involved in the α-oxidation of phytanic acid and of 2-hydroxy straight chain fatty acids, pointed towards a role of TPP in these processes. Until then, TPP had not been implicated in mammalian peroxisomal metabolism. The effect of thiamine deficiency on 2-HPCL and α-oxidation has not been studied, nor have possible adverse effects of deficient α-oxidation been considered in the pathogenesis of diseases associated with thiamine shortage, such as thiamine-responsive megaloblastic anemia (TRMA). Experiments with cultured cells and animal models showed that α-oxidation is controlled by the thiamine status of the cell/tissue/organism, and suggested that some pathological consequences of thiamine starvation could be related to impaired α-oxidation. Whereas accumulation of phytanic acid and/or 2-hydroxyfatty acids or their α-oxidation intermediates in TRMA patients given a normal supply of thiamine is unlikely, this may not be true when malnourished.

Keywords.

Beriberi 2-hydroxyfatty acids peroxisomes phytanic acid thiamine-responsive megaloblastic anemia vitamin B Wernicke-Korsakoff syndrome 

Copyright information

© Birkhäuser Verlag, Basel 2006

Authors and Affiliations

  • M. Sniekers
    • 1
  • V. Foulon
    • 1
  • G. P. Mannaerts
    • 1
  • L. Van Maldergem
    • 2
  • H. Mandel
    • 3
  • B. D. Gelb
    • 4
  • M. Casteels
    • 1
  • P. P. Van Veldhoven
    • 1
  1. 1.Departement Moleculaire Celbiologie, Afdeling Farmacologie, Faculteit GeneeskundeKatholieke Universiteit LeuvenLeuvenBelgium
  2. 2.Centre de Génétique Humaine – Maladies métaboliqueUniversité de LiègeLiègeBelgium
  3. 3.Metabolic Unit, Department of PediatricsRambam Medical CenterHaifaIsrael
  4. 4.Departments of Pediatrics and Human GeneticsMount Sinai School of MedicineNew YorkUSA