Presence of thiamine pyrophosphate in mammalian peroxisomes

<p>Abstract</p> <p>Background</p> <p>Thiamine pyrophosphate (TPP) is a cofactor for 2-hydroxyacyl-CoA lyase 1 (HACL1), a peroxisomal enzyme essential for the α-oxidation of phytanic acid and 2-hydroxy straight chain fatty acids. So far, HACL1 is the only known peroxisomal TPP-dependent enzyme in mammals. Little is known about the transport of metabolites and cofactors across the peroxisomal membrane and no peroxisomal thiamine or TPP carrier has been identified in mammals yet. This study was undertaken to get a better insight into these issues and to shed light on the role of TPP in peroxisomal metabolism.</p> <p>Results</p> <p>Because of the crucial role of the cofactor TPP, we reanalyzed its subcellular localization in rat liver. In addition to the known mitochondrial and cytosolic pools, we demonstrated, for the first time, that peroxisomes contain TPP (177 ± 2 pmol/mg protein). Subsequently, we verified whether TPP could be synthesized from its precursor thiamine, <it>in situ</it>, by a peroxisomal thiamine pyrophosphokinase (TPK). However, TPK activity was exclusively recovered in the cytosol.</p> <p>Conclusion</p> <p>Our results clearly indicate that mammalian peroxisomes do contain TPP but that no pyrophosphorylation of thiamine occurs in these organelles, implying that thiamine must enter the peroxisome already pyrophosphorylated. Consequently, TPP entry may depend on a specific transport system or, in a bound form, on HACL1 translocation.</p

Reflections upon the Mathematization of Mayotte’s Economy

International audienceThis chapter envisages that Mayotte's economy could be viewed as a significant issue for the modelization of complex systems in the systemic paradigm – a paradigm which has come into being since the second half of the 20th Century. Despite the long debate on the so-called mathematization of economics since the 19th Century, advanced knowledge in mathematics is a necessity for any postgraduate economist. Though there are several arguments for justifying the mathematization of economics, it is sufficient in the chapter to group them into two categories, which are linked: the ontological argument and the linguistic one. The chapter uses examples to show the fact that Mayotte's formal economy cannot be strictly separated from informal activities and that their interactions, difficult to mathematize traditionally, might be viewed as issues for the modelization of complex systems

Biochemistry and genetics of inherited disorders of peroxisomal fatty acid metabolism[S]

In humans, peroxisomes harbor a complex set of enzymes acting on various lipophilic carboxylic acids, organized in two basic pathways, α-oxidation and β-oxidation; the latter pathway can also handle ω-oxidized compounds. Some oxidation products are crucial to human health (primary bile acids and polyunsaturated FAs), whereas other substrates have to be degraded in order to avoid neuropathology at a later age (very long-chain FAs and xenobiotic phytanic acid and pristanic acid). Whereas total absence of peroxisomes is lethal, single peroxisomal protein deficiencies can present with a mild or severe phenotype and are more informative to understand the pathogenic factors. The currently known single protein deficiencies equal about one-fourth of the number of proteins involved in peroxisomal FA metabolism. The biochemical properties of these proteins are highlighted, followed by an overview of the known diseases