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Thiamine was the 1 st vitamin ( vit al amin e) ever discovered.

Thiamine pyrophosphate. Thiamine was the 1 st vitamin ( vit al amin e) ever discovered. Thiamine deficiency results in a disease called beri-beri. (Beri-beri is a Malay word meaning “extreme lassitude”.). Beri-Beri was first described by Dutch physician Nicolaas Tulp in 1652.

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Thiamine was the 1 st vitamin ( vit al amin e) ever discovered.

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  1. Thiamine pyrophosphate Thiamine was the 1st vitamin (vital amine) ever discovered. Thiamine deficiency results in a disease called beri-beri. (Beri-beri is a Malay word meaning “extreme lassitude”.)

  2. Beri-Beri was first described by Dutch physician Nicolaas Tulp in 1652. Tulp also commissioned Rembrandt to paint “The Anatomy Lesson”. Thiamine pyrophosphate functions in decarboxylation of a-ketoacids.

  3. Direct decarboxylation of an a-keto acid would be difficult because there is no way of delocalising the negative charge that would develop on the a-carbon. TPP facilitates decarboxylation.

  4. + H S S - C C C H C C C + N + N C H C H 3 3 The important part of TPP is the thiazole ring. One of the carbon atoms can easily lose a proton to form a carbanion that is stabilised by the ring.

  5. O O H C S + O C - H C C C H C 3 + N C H 3 O O H C S C H O C C C + N C H C H 3 3 This adds to the ketone group of the a-ketoacid.

  6. O C O - S S C C H O C C H O C C C C N + N C H C H C H C H 3 3 3 3 Decarboxylation generates a carbanion on the C atom derived from C2 of the a-keto acid. The charge can be delocalised over the thiazole ring.

  7. H O O H O O C C C H 3 H O O C C C H 3 O C C H 3 - S C S H O C C C - C C + N C H C H C 3 3 + N C H 3 The hydroxyethyl carbanion (sometimes referred to as activated acetaldehyde) can be transferred to an acceptor molecule like pyruvate (for VAL biosynthesis, see below), or a-ketobutyrate (for ILE biosynthesis) or to CoA via lipoic acid.

  8. H S S O C C H 3 L i p o y l d o m a i n + H S S L i p o y l d o m a i n S - C H O C C C + N C H C H 3 3 With pyruvate dehydrogenase, the hydroxyethyl carbanion is transferred to a lipoic acid cofactor.

  9. H S S H L i p o y l d o m a i n O H C C S C o A 3 H S C o A + H S S O C C H 3 L i p o y l d o m a i n The acyl group is then transferred to coenzyme A.

  10. S S + N A D H + H + L i p o y l d o m a i n N A D H S S H L i p o y l d o m a i n Finally the dihydrolipoamide is re-oxidised by NAD+ . a-ketoglutarate DH: same story except that the a-keto acid is a –ketoglutarate and the product is succinyl CoA

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