Vitamin B1 (Thiamin)

Mechanism

Activation and coenzyme functions

After its cellular uptake, thiamine is phosphorylated by the cytosolic enzyme thiamine pyrophosphokinase to become the essential active coenzyme: Thiamin Pyrophosphate (TPP) or thiamine diphosphate. TPP acts as a cofactor for mitochondrial multienzyme complexes involved in oxidative metabolism:

1. Pyruvate Dehydrogenase (PDH) Complex: Oxidative decarboxylation of pyruvate to acetyl-CoA, serving as a critical link between cytosolic glycolysis and the Krebs cycle.
2. α-Ketoglutarate Dehydrogenase Complex: Catalyzes the conversion of α-ketoglutarate to succinyl-CoA in the Krebs cycle.
3. Branched Chain α-Ketoacid Dehydrogenase Complex (BCKDH): Essential for the catabolism of the amino acids leucine, isoleucine and valine.
4. Transketo-lase (Pentose Phosphate Pathway): Transfer of carbon fragments in the cytosol to generate NADPH and ribose-5-phosphate.

The TPP-mediated limiting reaction in the pyruvate dehydrogenase complex is described by:

Pharmacokinetics

Pharmacokinetic Aspects and Clinical Syndromes

It is actively absorbed in the duodenum by proton gradient-coupled transporters called THTR-1 and THTR-2. Its active uptake capacity is highly saturable (> 5 mg per oral dose), so the administration of massive doses occurs by passive diffusion with lower efficiency.

Severe thiamine deficiency causes two clinical entities:

• Wet Beriberi: Cardiovascular dysfunction characterized by severe peripheral vasodilation, high cardiac output congestive heart failure, and marked peripheral edema.
• Dry Beriberi and Wernicke-Korsakoff Encephalopathy: Acute neuropsychiatric syndrome observed primarily in patients with chronic alcoholism or after bariatric surgery, characterized by the classic triad of ophthalmoplegia, cerebellar ataxia and a state of global confusion.

Indicators and dose

Physiopathology of Energy Compromise of Deficiency (Lactic Acidosis)

In the absence of TPP, the activity of PDH and α-ketoglutarate dehydrogenase complexes is critically decreased, blocking aerobic mitochondrial metabolism. To generate ATP, cells massively divert accumulated pyruvate into the anaerobic pathway via lactate dehydrogenase, converting it to lactate. This biochemical change explains the appearance of severe lactic acidosis and the energy failure of tissues with high metabolic demand such as the myocardium and the central nervous system.

Security

Glucose Infusion Alert without Prior Thiamine

In patients with suspected chronic thiamine deficiency (malnourished, alcoholic), rapid intravenous administration of concentrated glucose solutions without prior thiamine intake can acutely precipitate irreversible Wernicke's encephalopathy. The massive glucose load increases the metabolic demand for cellular TPP, depleting residual brain reserves instantly. Parenteral thiamine should always be administered beforehand.