1. Thiamine pyrophosphate: An essential cofactor for the α-oxidation in mammals – implications for thiamine deficiencies?
- Author
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Sniekers, M., Foulon, V., Mannaerts, G. P., Van Maldergem, L., Mandel, H., Gelb, B. D., Casteels, M., and Van Veldhoven, P. P.
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VITAMIN B1 ,OXIDATION ,MAMMALS ,ANIMAL disease models ,EXPERIMENTAL pathology ,ANEMIA ,THIAMIN pyrophosphate ,VITAMIN B1 deficiency - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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