Vitamin B1 (Thiamine)


Thiamine is a water-soluble B vitamin and plays an essential role in normal cellular functions, growth and development. Thiamine is found in high concentrations in the skeletal muscle, heart, liver, kidneys and brain. Mammals, including humans cannot synthesize thiamine so it has to be obtained from diet via intestinal absorption. Absorption of vitamin B1 involves a specialized pH-dependent, Na+- independent carrier mediated mechanism (1). In order to become a coenzyme thiamine has to acquire a pyrophosphate group. This process occurs intracellularly in a reaction catalyzed by the enzyme thiamine pyrophosphokinase at the expense of cellular ATP. Thiamine uptake is enhanced by thiamine deficiency and reduced by the thyroid hormone and diabetes (2).


Thiamine pyrophosphate (the coenzyme form of vitamin B1). The thiazolium ring is the moiety involved in the catalytic process.

  • Essential for energy production in carbohydrate/amino acid metabolism. TPP deficiency may lead to pyruvate accumulation, hence inhibition of energy production.
  • Essential for nerve cell function. A low level of thiamine in the brain impairs not only the energy production (ATP) but also the synthesis of the neurotransmitter acetylcholine. Acetylcholine is synthesized from choline and acetyl-CoA (reaction catalyzed by choline acetyltransferase).
  • Potentiates and mimics the effects of the neurotransmitter acetylcholine in the brain. Total thiamine content in cholinergic nerve terminals is comparable with that of acetylcholine and the phosphorylation state of thiamine changes with the release of acetylcholine. When scopolamine (a chemical that interferes with the neurocognitive function of the brain) was given to healthy subjects together with higher doses of vitamin B1, the adverse effects of scopolamine were greatly reduced. These findings suggest a cholino-mimetic effect of vitamin B1 in the central nervous system (3).
  • Promotes growth and good muscle tone.
  • Interactions: Thiamine is intricatelly involved with the other B vitamins in energy metabolism. Magnesium is required in the conversion of thiamine to the coenzyme form. Alcohol inactivates vitamin B1.
  • Health benefits: Supplementation is useful in cardiovascular disease, diabetes mellitus, varicose veins, inflammatory bowel disease.
  • Best food sources: brewer's yeast, wheat germs, soybeans, sunflower seeds, brown rice, fresh vegetables.
Some of the reactions in which TPP is involved are listed below:
1. Thiamine pyrophosphate (TPP) is one of the coenzymes required by the pyruvate dehydrogenase multienzyme complex for the decarboxylation of pyruvate:

pyruvate + CoA-SH + NAD+ ----> acetyl-CoA + CO2 + NADH

2. TPP is also required in the degradation of branched-chain amino acids isoleucine, leucine and valine. The second stage in this process is catalyzed by a-ketoisovalerate dehydrogenase, a multienzyme complex that employs the coenzymes TPP, FAD, NAD+ and the lipoamide.

3. TPP is involved in a reaction of the pentose phosphate pathway, i.e.in the formation of sedoheptulose-7-phosphate. The enzyme that catalyzes this reaction (transketolase) requires TPP as coenzyme. The pentose phosphate pathway is one of the generators of reducing power (NADPH) necessary for biosynthetic processes as well as for several reductive processes, such as the regeneration of GSH in the erythrocytes whose function is to protect the integrity of cell membrane by removing the hydrogen peroxide and lipid hydroperoxides through the reaction catalyzed by GSH-peroxidase.

References
1. Dudeja, P.K. et al. (2001) Am.J.Physiol. Cell Physiol. 281: C786-C792. Mechanism of thiamine uptake by human jejunal
    brush-border membrane vesicles.
2. Rindi, G. and Laforenza, U. (2000) Proc.Soc.Exp.Med. 224(4) 246-255. Thiamine intestinal transport and related issues: recent aspects.
3. Meador, K.J. et al. (1993) Ann.Neurol. 34(5), 724-726. Evidence for a central cholinergic effect of high-dose thiamine.