Thiamine (vitamin B1) is conveed intracellularly to its active form, thiamine pyrophosphate, which is an essential cofactor in intermediate carbohydrate metabolism. Thiamine acts as a coenzyme for enzymes involved in the tricarboxylic acid cycle, which plays a critical role in the production of energy from food, and the pentose-phosphate pathway, which produces an impoant intermediate, ribose-5-phosphate, required for the synthesis of ATP, GTP, DNA, RNA, and NADPH. The brain is paicularly vulnerable to thiamine deficiency because it relies exclusively on carbohydrates for immediate energy demands. The selective vulnerability of ceain structures accounts for the specific clinical manifestations of Wernicke encephalopathy. Thiamine pyrophosphate (TPP), the physiologically active form of thiamine, is required for the activity of pyruvate dehydrogenase (PDH). PDH catalyzes oxidative decarboxylation of pyruvate to acetyl-CoA, regulating entry into the citric acid cycle for metabolites leaving glycolysis. The PDH complex is comprised of 3 separate enzymes: pyruvate dehydrogenase (decarboxylase), dihydrolipoamide transacetylase and dihydrolipoamide dehydrogenase. Besides TPP, the complex also requires CoA, NAD, FAD, and lipoic acid as coenzymes. The mechanism of TPP action includes formation of a carbanion that can attack the electron-deficient keto carbon of pyruvate. In addition, TPP functions as a coenzyme for alpha-ketoglutarate dehydrogenase and transketolase. Pyridoxal phosphate serves as a coenzyme for glycogen phosphorylase. Vitamin B12 acts as a cofactor of L-methylmalonyl-CoA mutase, which catalyzes conversion of L-methylmalonyl-CoA to succinyl-CoA. Methionine synthase activation leads to synthesis of methionine from homocysteine with folic acid as a coenzyme.