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Thiamin function, metabolism, uptake, and transport

Biochemistry. 2014 ;53(5):821-35.

Manzetti S, Zhang J, van der Spoel D.

Uppsala Center for Computational Chemistry, Science for Life Laboratory, Department for Cell and Molecular Biology, University of Uppsala , Box 596, 751 24 Uppsala, Sweden.

 

 Abstract

Vitamins are crucial components in the diet of animals and many other living organisms. One of these essential nutrients, thiamin, is known to be involved in several cell functions, including energy metabolism and the degradation of sugars and carbon skeletons. Other roles that are connected to this vitamin are neuronal communication, immune system activation, signaling and maintenance processes in cells and tissues, and cell-membrane dynamics. Because of the key functions of thiamin, uptake and transport through the body are crucial. Its uptake route is relatively complex, encompassing a variety of protein families, including the solute carrier anion transporters, the alkaline phosphatase transport system, and the human extraneuronal monoamine transporter family, some of which are multispecific proteins. There are two known structures of protein (subunits) involved in thiamin uptake in prokaryotes. Binding of thiamin to these proteins is strongly guided by electrostatic interactions. The lack of structural information about thiamin binding proteins for higher organisms remains a bottleneck for understanding the uptake process of thiamin in atomic detail. This review includes recent data on thiamin metabolism, related deficiencies and pathologies, and the latest findings on thiamin binding transporters.

 

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Figure legend: The Thiamin transporter protein (silver) from protein databank structure 3RLB is shown with a bound thiamin molecule (orange). The protein is embedded in a membrane of mixed phospholipid composition. Thiamin or Vitamin B1 is an essential nutrient usually ingested from plants. Deficiency of Thiamin can lead to grave symptoms and, eventually, death. Beriberi is a common name for this disease. Recent findings of ailing and dying wild birds and mammals have been attributed to thiamin deficiency but no evidence has been put forward, other than that the condition of these animals could be reversed by injecting thiamin. In the present paper we review Thiamin function, metabolism, uptake and transport, with special attention for molecular level information. A long-term goal of this research is to predict, based on known protein structures, whether other molecules, e.g. pollutants, might block Thiamin uptake from nutrients. Such predictions would allow a directed search for these compounds in affected animals.

 

Thiamin Function, Metabolism, Uptake, and Transport - global medical discovery