The human body requires Vitamin B1 to function properly, which is why it is referred to as a vitamin. A deficiency of thiamine most commonly results in Wernicke-Korsakoff’s syndrome or beriberi, however thiamine can be found in many food sources with the most typical being grains. This explains why Korsakoff’s in first world countries is really only seen in alcoholics who are known to not have the best of diets. Shown below is the full chemical structure of thiamine pyrophosphate, which is the active form of the compound.
Thiamine pyrophosphate tpp
However the chemical structure is complex and really all the magic happens in the cyclic ring of the molecule.
The top carbon active because being double bonded to positively charged nitrogen it can easily be deprotonated and form its carbanion structure shown in the image to the left. This carbanion is vital for the magic of vitamin B and as a co-enzyme to perform transketolase reactions as well as α-decarboxylation. So next lets go over those two reactions with a little explanation.
Pyruvate is the product of glycolysis and can enter the Kreb’s cycle only as Acetyl-CoA requiring α-COO group to be removed which is performed by the Pyruvate Dehydrogenase (PDH) enzyme. We now know that PDH requires the TPP cofactor to allow this reaction, but what is the mechanism and why is thiamine required. PDH like any enzyme holds its substrates in close proximity to allow the specific reaction to occur at a much faster rate than if the substrates were alone in solution. The PDH binds both TPP and pyruvate to help the reaction proceed and release acetyl-CoA. Thiamine is perfect for this reaction because the carbanion binds the carbonyl carbon of pyruvate. When bound together the carbons are not the same, now the carbonyl carbon can be considered to be the thiamine carbon doubly bound to nitrogen and the pyrivate carbonyl carbon is now an alpha carbon.
This means the α-COO group has become a ß-COO and because of the nature of chemistry ß-oxidation is very simple process and happens spontaneously. So what does this mean for us if we don’t consume enough thiamine? It means our break down of sugar is stunted, but also any α-ketoacid dehydrogenase enzyme is also stunted because the requirement for TPP.