title: Thiamine pyrophosphate: an essential cofactor for the alpha-oxidation in mammals--implications for thiamine deficiencies?
abstract: The identification of 2-hydroxyphytanoyl-CoA lyase (2-HPCL), a thiamine pyrophosphate (TPP)-dependent peroxisomal enzyme involved in the alpha-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 alpha-oxidation has not been studied, nor have possible adverse effects of deficient alpha-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 alpha-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 alpha-oxidation. Whereas accumulation of phytanic acid and/or 2-hydroxyfatty acids or their alpha-oxidation intermediates in TRMA patients given a normal supply of thiamine is unlikely, this may not be true when malnourished.
authors.affiliation: Departement Moleculaire Celbiologie, Afdeling Farmacologie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, O & N1, Herestraat 49, Box 601, 3000, Leuven, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Sniekers
authors.forename: V
authors.initials: V
authors.lastname: Foulon
authors.forename: G P
authors.initials: GP
authors.lastname: Mannaerts
authors.forename: L
authors.initials: L
authors.lastname: Van Maldergem
authors.forename: H
authors.initials: H
authors.lastname: Mandel
authors.forename: B D
authors.initials: BD
authors.lastname: Gelb
authors.forename: M
authors.initials: M
authors.lastname: Casteels
authors.forename: P P
authors.initials: PP
authors.lastname: Van Veldhoven
mesh_terms: D000749:Anemia, Megaloblastic / Q000378:metabolism*; D000818:Animals; D019755:Carbon-Carbon Lyases / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D010084:Oxidation-Reduction; D010831:Phytanic Acid / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013831:Thiamine / Q000378:metabolism; D013832:Thiamine Deficiency / Q000378:metabolism*; D013835:Thiamine Pyrophosphate / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D010831:Phytanic Acid; D019755:Carbon-Carbon Lyases; C121516:2-hydroxyphytanoyl-coenzyme A lyase; D013835:Thiamine Pyrophosphate; D013831:Thiamine