Vitamin B1 (Thiamine)
Vitamins

Thiamine is a water soluble vitamin which acts as a coenzyme in pyruvic acid and other ketoacids decarboxylation reactions. It is found in foods of plant (wheat germ, cereals, legumes) and animal origin (beef and pork, especially the liver, brain, kidneys and intestines). In the first it is mostly in the free form, while in the latter it can be phosphorylated in both mono and diphosphate.
Its structure is composed of a thiazole ring joined by a methylene link to a pyrimidine ring.
In the intestine, thiamine can be absorbed by a process of active or passive transport by enterocytes, which then release it into the bloodstream in the free or phosphorylated form (thiamine monophosphate). In the tissues it is converted into its active form, thiamine pyrophosphate (TPP), by the enzyme thiamine pyrophosphate synthetase. Since the excess is excreted in the urine, it does not have toxicity.

Thiamine Pyrophosphate on Wikipedia

Reactions

The functional part of thiamine pyrophosphate, the thiazole ring, has an acid proton on the carbon atom C2. His detachment produces a carbanion, which is the active species in reactions. The carbanion binds to carbonyl groups, while the thiazole ring is in position to capture electrons, facilitating the reaction.

Pentose phosphate pathway
In some tissues, glucose 6-phosphate is oxidized to pentose phosphate by the pentose phosphate pathway. The electron acceptor is NADP+, which is reduced to NADPH. In the non-oxidative phase of this pathway, the pentose phosphate produced is recycled to glucose 6-phosphate. The enzyme transketolase transfers a two carbon atoms fragment from a ketose donor to an aldose acceptor. The TPP acts as a cofactor, stabilizing the carbanion during the transfer.

Acetyl-CoA synthesis
The pyruvate produced by glycolysis has to be oxidized to acetyl-CoA by the action of the pyruvate dehydrogenase multienzymatic complex. The first part of the transformation is catalyzed by the enzyme E1 (pyruvate dehydrogenase), which requires the intervention of the TPP as a coenzyme. The C1 atom of pyruvate is released as CO2 and the C2 atom is bound to the TPP as a hydroxyethylic group. This is then oxidized to acetate, which continues in the chain of reactions in the complexes E2 and E3, while the TPP, now free again, can start a new cycle.

Citric acid cycle
Acetyl-CoA enters the citric acid cycle, through which it is enzymatically oxidized to CO2. The energy released is stored in the carriers NADH and FADH2. These, oxidizing themselves, give their electrons, through the respiratory chain, to the oxygen. The energy released by this process is used to produce ATP via oxidative phosphorylation.
Thiamine pyrophosphate intervenes in α-ketoglutarate oxidation to succinyl-CoA operated by the α-ketoglutarate dehydrogenase complex. This reaction proceeds in a manner similar to the one catalyzed by pyruvate dehydrogenase complex: the TPP is linked to the first of the three enzymes that compose the complex.

Oxidation of branched chain amino acids
Leucine, isoleucine and valine are not degraded in the liver, but are oxidized in the muscle, adipose tissue, kidney and brain. These tissues have an aminotransferase that is absent in the liver, which converts amino acids into the corresponding ketoacids. Thereafter, the dehydrogenase complex for the branched chain α-ketoacids oxidatively decarboxylates them, producing the respective acyl-CoA and releasing CO2. This complex operates similarly to that of the pyruvate dehydrogenase and α-ketoglutarate dehydrogenase, using thiamine pyrophosphate in the first part of the reaction.

Thiamine deficiency

Thiamine is not stored in the body, and its deficiency in the diet, often found in populations that feed almost exclusively with polished white rice or in chronic alcoholics, causes problems after a few days, especially in carbohydrates metabolism. In particular, the plasma level of α-ketoacids increases and the transketolasic activity of erythrocytes lowers, parameter used to assess the nutritional status of thiamine. Minor symptoms are dryness of the skin with tendency to acne and weakness of hair, nails and other skin appendages. The chronic deficiency causes alterations in the central and peripheral nervous system and cardiovascular system, sometimes with fatal outcomes.

Supplementary Thiamine Is Still Important in Alcohol Dependence, 2013

Beriberi
Oxidation of pyruvate in the brain is a particularly important process, since this organ uses as the only source of energy the aerobic oxidation of glucose. So, thiamine deficiency causes a decrease of neuronal function. The most common clinical signs are fatigue, irritability, poor memory and, subsequently, peripheral nerve pain and loss of neurologic reflexes. These symptoms mainly concern the lower limbs, but can spread to the upper. The disease also affects the gastrointestinal system (lack of appetite, indigestion, constipation, decrease of HCl in the stomach) and cardiovascular system (cardiac arrhythmias, relaxation of arteries and veins leading to edema in the legs, heart dilatation and circulatory collapse).

Beriberi on Pubmed

Wernicke-Korsakoff syndrome
Decrease in the levels of thiamine pyrophosphate leads to a lowered speed of the pentose phosphate pathway. This is manifested by memory loss, confusion and partial paralysis.

NINDS Wernicke-Korsakoff Syndrome Information Page
Mechanisms of selective neuronal cell death due to thiamine deficiency, 1999

Thiamine and aging
Thiamine preserves the nervous system function, protecting the myelin sheath from degeneration. It can also act directly as an antioxidant and prevent liver cytotoxicity and the formation of free radicals. By not yet clarified mechanisms it helps to prevent the formation of kidney stones and the consequences of uncompensated diabetes.
While apparently effective in treating chronic diseases, treatment with thiamine is not often used.

Thiamine on MedlinePlus
Is thiamine deficiency in elderly people related to age or co-morbidity?, 2000

Heba Elhadidy
Matteo Cucino