Thiamine or thiamin, sometimes called aneurin, is a water-soluble vitamin of the B complex (vitamin B1), whose phosphate derivatives are involved in many cellular processes. The best characterized form is thiamine diphosphate (ThDP), a coenzyme in the catabolism of sugars and amino acids. In yeast, ThDP is also required in the first step of alcoholic fermentation.

Thiamine is synthesized in bacteria, fungi and plants. Animals must cover all their needs from their food and insufficient intake results in a disease called beriberi affecting the peripheral nervous system (polyneuritis) and/or the cardiovascular system, with fatal outcome if not cured by thiamine administration. In less severe deficiency, nonspecific signs include malaise, weight loss, irritability and confusion. Today, there is still a lot of work devoted to elucidating the exact mechanisms by which thiamine deficiency leads to the specific symptoms observed (see below). Finally, new thiamine phosphate derivatives have recently been discovered, emphasizing the complexity of thiamine metabolism and the need for more research in the field.

Absorption and transport

Absorption

Thiamine is released by the action of phosphatase and pyrophosphatase in the upper small intestine. At low concentrations the process is carrier mediated and at higher concentrations, absorption occurs via passive diffusion. Active transport is greatest in the jejunum and ileum (it is inhibited by alcohol consumption and by folic deficiency. Decline in thiamine absorption occurs at intakes above 5 mg. The cells of the intestinal mucosa have thiamine pyrophosphokinase activity, but it is unclear whether the enzyme is linked to active absorption. The majority of thiamine present in the intestine is in the pyrophosphorylated form ThDP, but when thiamine arrives on the serosal side of the intestine it is often in the free form. The uptake of thiamine by the mucosal cell is likely coupled in some way to its phosphorylation/dephosphorylation. On the serosal side of the intestine, evidence has shown that discharge of the vitamin by those cells is dependent on Na+-dependent ATPase.

Bound to Serum Proteins

The majority of thiamine in serum is bound to proteins, mainly albumin. Approximately 90% of total thiamine in blood is in erythrocytes. A specific binding protein called thiamine-binding protein (TBP) has been identified in rat serum and is believed to be a hormonally regulated carrier protein that is important for tissue distribution of thiamine.

Cellular Dptake

Uptake of thiamine by cells of the blood and other tissues occurs via active transport and passive diffusion. About 80% of intracellular thiamine is phosphorylated and most is bound to proteins. In some tissues, thiamine uptake and secretion appears to be mediated by a soluble thiamine transporter that is dependent on Na+ and a transcellular proton gradient.

Tissue Distribution

Human storage of thiamine is about 25 to 30 mg with the greatest concentrations in skeletal muscle, heart, brain, liver, and kidneys. ThMP and free (unphosphorylated) thiamine is present in plasma, milk, cerebrospinal fluid, and likely all extracellular fluids. Unlike the highly phosphorylated forms of thiamine, ThMP and free thiamine are capable of crossing cell membranes. Thiamine contents in human tissues are less than those of other species.

Excretion

Thiamine and its acid metabolites (2-methyl-4-amino-5-pyrimidine carboxylic acid, 4-methyl-thiazole-5-acetic acid and thiamine acetic acid) are excreted principally in the urine.