Thiamin coenzymes

B, Thiamin Coenzyme in pyruvate and a-ketoglutarate, dehydrogenases, and transketolase poorly defined function in nerve conduction Peripheral nerve damage (beriberi) or central nervous system lesions (Wernicke-Korsakoff syndrome)... 

Structures of Thiamin-Dependent Enzymes 4. The Variety of Enzymatic Reactions Involving Thiamin 5. Oxidative Decarboxylation and 2-Acetylthiamin Diphosphate. 6. Thiamin Coenzymes in Nerve Action 753. .. Table 14-4 Some Pyruvoyl Enzymes... 

Thiamine, biotin and pyridoxine (vitamin B) coenzymes are grouped together because they catalyze similar phenomena, i.e., the removal of a carboxyl group, COOH, from a metabolite. However, each requires different specific circumstances. Thiamine coenzyme decarboxylates only alpha-keto acids, is frequently accompanied by dehydrogenation, and is mainly associated with carbohydrate metabolism. Biotin enzymes do not require the alpha-keto configuration, are readily reversible, and are concerned primarily with lipid metabolism. Pyridoxine coenzymes perform nonoxidative decarboxylation and are closely allied with amino acid metabolism. 

Exercise 25-32 Write equations for a base-induced decomposition of the modified thiamine coenzyme, 11, to ethanal and thiamine pyrophosphate. 

In practice, donor substituents make it possible actually to isolate a range of carbenes 4.105. With somewhat less stabilisation, the carbene 4.106, although it is only found as a reactive intermediate, is exceptionally easy to form. It is the key intermediate in all the metabolic steps catalysed by thiamine coenzymes, and its reactions are characterised by its nucleophilicity. Similarly, dimethoxycarbene 4.107 reacts as a nucleophile with electrophiles like dimethyl maleate to give the intermediate 4.108, and hence the cyclopropane 4.109, but it does not insert into unactivated alkenes. 

B, Thiamin Coenzyme in pyruvate and Peripheral nerve damage... 

Nakanishi, I., Itoh, S., Suenobu, T, Fukuzumi, S. (1997a), Electron transfer properties of active aldehydes derived from thiamin coenzyme analogues, Chem. Commun. 19, 1927-1928. 

The donor substituents have more remarkable effect than electron-withdrawing substituents because they make it possible to isolate a good range of carbenes such as 148 [63-65]. The carbene 149 is the key intermediate in the metabolic pathways catalyzed by the thiamine coenzymes. These reactions proceed by the nucleophilic addition of the carbene to the substrates such as aldehydes [66]. 

PDH deficiency results in raised blood concentrations of pyruvate, lactate and alanine. Some patients respond to supplementation with lipoic acid or thiamin (coenzymes for PDH). Treatment with a low carbohydrate, ketogenic diet has been advocated but with limited success. (The ketone bodies readily cross the blood-brain barrier and their catabolism produces acetyl CoA independently of PDH.)... 

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