Thiamin was the first of the water-soluble B vitamins to be identified as an essential nutrient. Chemically, it consists of a substituted pyrimidine ring (A) and a thiazole, connected by a methyl group. The term vitamin Bj encompasses several compounds with thi-amin-like effects. Naturally occurring Bj consists mostly of thiamin phosphates. In pharmaceuticals, water-soluble thiamin derivatives like thiamin hydrochloride or nitrate as well as lipophilic thiamin analogues like benfo-tiamine or fursultiamine are used.
Absorption of thiamin occurs predominantly in the jejunum after its release in the intestinal lumen during digestion. The active transport mechanism for water-soluble thiamin is saturable and rate-limiting. At higher luminal concentrations, some minor passive diffusion occurs. Overall, absorption at physiological doses is near 100%, while it drops to ~25% at pharmacological dosages. Lipophilic thiamin analogues pass through cell membranes more easily and are, therefore, absorbed in amounts corresponding to intakes. In the intestinal mucosa, free thiamin is converted to active thiamin diphosphate (TDP)—a process that consumes ATP—released into the bloodstream, bound to albumin, and transported to the target cells. The entire body contains ~30 mg thiamin, 40 % of which is found in the musculature. Since its storage is so limited and because of its short half-life, daily exogenous supply is required. Excretion is mainly renal, either as thiamin, as its sulfate ester, or as other, hitherto unidentified, metabolites.
The biochemical functions of thiamin are based mostly on its role as the TDP coenzyme. Beyond that, specific nervous system functions of thiamin tri-phosphate (TTP) are under discussion regarding involvement of TTP in the Na+-permeability of membranes. Transketolase is a thiamin-dependent key enzyme, the activity of which is also used to assess thiamin status (B). It catalyzes the reversible transfer of a C2 fragment during the pentose phosphate cycle, thereby converting various aldoses into ketoses and vice versa. Pyruvate, the end product of glycolysis and of the breakdown of glucogenic amino acids, is converted to acetyl by the thiamin-dependent pyruvate dehy-drogenase (C) after which it can enter the citrate cycle as acetyl-CoA. The formation of succinyl-CoA during the citrate cycle requires the enzyme a-ketoglutarate dehydrogenase, which also depends on a thiamin cofactor.
Generally, thiamin is involved in reactions (D) that lead either to decarboxylation of a-keto acids (1), formation of a-hydroxy ketones (2), or transfer of an a-keto R-group (3,4). During an intermediate stage (5), a negatively charged C atom is formed, the charge of which is stabilized by TDP, making it available for further reactions at the enzyme complex.
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