Thiamine Status in Humans and Content of Phosphorylated Thiamine Derivatives in Biopsies and Cultured Cells

Abstract

BackgroundThiamine (vitamin B1) is an essential molecule for all life forms because thiamine diphosphate (ThDP) is an indispensable cofactor for oxidative energy metabolism. The less abundant thiamine monophosphate (ThMP), thiamine triphosphate (ThTP) and adenosine thiamine triphosphate (AThTP), present in many organisms, may have still unidentified physiological functions. Diseases linked to thiamine deficiency (polyneuritis, Wernicke-Korsakoff syndrome) remain frequent among alcohol abusers and other risk populations. This is the first comprehensive study on the distribution of thiamine derivatives in human biopsies, body fluids and cell lines.Methodology and Principal FindingsThiamine derivatives were determined by HPLC. In human tissues, the total thiamine content is lower than in other animal species. ThDP is the major thiamine compound and tissue levels decrease at high age. In semen, ThDP content correlates with the concentration of spermatozoa but not with their motility. The proportion of ThTP is higher in humans than in rodents, probably because of a lower 25-kDa ThTPase activity. The expression and activity of this enzyme seems to correlate with the degree of cell differentiation. ThTP was present in nearly all brain and muscle samples and in ∼60% of other tissue samples, in particular fetal tissue and cultured cells. A low ([ThTP]+[ThMP])/([Thiamine]+[ThMP]) ratio was found in cardiovascular tissues of patients with cardiac insufficiency. AThTP was detected only sporadically in adult tissues but was found more consistently in fetal tissues and cell lines.Conclusions and SignificanceThe high sensitivity of humans to thiamine deficiency is probably linked to low circulating thiamine concentrations and low ThDP tissue contents. ThTP levels are relatively high in many human tissues, as a result of low expression of the 25-kDa ThTPase. Another novel finding is the presence of ThTP and AThTP in poorly differentiated fast-growing cells, suggesting a hitherto unsuspected link between these compounds and cell division or differentiation.

Molecular Identification and Functional Characterization of the Human Colonic Thiamine Pyrophosphate Transporter

“…Free thiamine could then move out of the cell across the basolateral membrane via the previously characterized THTR-1, which is expressed in colonocytes (12). As for TMP, this thiamine metabolite does exist in considerable amounts in the plasma (30), and, thus, it is possible that it can also leave the colonocyte via a yet to be identified transport system. Whether TPP itself can also cross the colonic basolateral membrane (knowing that there is some TPP in the plasma (31)) is not clear and requires further investigations.…”

Biological functions of thiamine derivatives: Focus on non-coenzyme roles

“…This 25-kDa cytoplasmic protein is a highly efficient ThTPase ubiquitously expressed in adult mammalian tissues. However, it seems to be most 5 abundant in highly differentiated cells while it is hardly detectable in cultured cells, suggesting that the expression of this enzyme is linked to the degree of cellular differentiation 20,21 .…”

“…However, in those organisms where 25-kDa ThTPase is absent (chicken) or catalytically inefficient (fish, pig), cytosolic ThTP indeed accumulates and, in skeletal muscles and electric organs its levels can even exceed those of ThDP, but without apparent toxic effect 21 . It is possible that ThTP has mainly a mitochondrial role, i. e., intramitochondrial ThTP synthesized by F o F 1 -ATP synthase is the physiologically relevant pool, while cytosolic ThTP synthesized by adenylate kinase would be only a by-product of this enzyme activity.…”

Efficient Transdermal Delivery of Benfotiamine in an Animal Model

“…Apparently, in both forms (type 1 and type 2) of diabetic condition there is about 70 % thiamine deficiency as measured in the plasma of diabetic patients [13][14][15] but the physiological mechanism associated with this deficiency has not been clarified yet. However, a number of studies found an altered thiamine handling in the kidneys of diabetic patients [16][17][18].…”

“…However, a number of studies found an altered thiamine handling in the kidneys of diabetic patients [16][17][18]. Benfotiamine, (S-benzoylthiamine-Omonophosphate), a derivative of the vitamin B1 or thiamine, has a much higher bioavailability than thiamine and, as a result, accumulates in the target tissues much more than thiamine itself [15,19,20]. Thiamine absorption from oral benfotiamine is approximately five times greater than from conventional thiamine supplements [21][22][23].…”