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Date: 22-11-2021
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Thiamine (Vitamin B1)
Thiamine pyrophosphate (TPP) is the biologically active form of the vitamin, formed by the transfer of a pyrophosphate group from ATP to thiamine (Fig. 1). TPP serves as a coenzyme in the formation or degradation of α-ketols by transketolase (Fig. 2A) and in the oxidative decarboxylation of α-keto acids (Fig. 2B).
Figure 1: A. Structure of thiamine and its coenzyme form, thiamine pyrophosphate. B. Structure of intermediate formed in the reaction catalyzed by pyruvate dehydrogenase. C. Structure of intermediate formed in the reaction catalyzed by α-ketoglutarate dehydrogenase. AMP = adenosine monophosphate.
Figure 2: Reactions that use thiamine pyrophosphate (TPP) as coenzyme. A. Transketolase. B. Pyruvate dehydrogenase and α-ketoglutarate dehydrogenase. [Note: TPP is also used by branched-chain α-keto acid dehydrogenase.] P = phosphate; CoA = coenzyme A; CO2 = carbon dioxide.
A. Clinical indications for thiamine
The oxidative decarboxylation of pyruvate and α-ketoglutarate, which plays a key role in energy metabolism of most cells, is particularly important in tissues of the CNS. In thiamine deficiency, the activity of these two dehydrogenase-catalyzed reactions is decreased, resulting in decreased production of ATP and, therefore, impaired cellular function. TPP is also required by branched-chain α-keto acid dehydrogenase of muscle . [Note: It is the decarboxylase of each of these α-keto acid dehydrogenase multienzyme complexes that requires TPP.] Thiamine deficiency is diagnosed by an increase in erythrocyte transketolase activity observed with addition of TPP.
1. Beriberi: This severe thiamine-deficiency syndrome is found in areas where polished rice is the major component of the diet. Adult beriberi is classified as dry (characterized by peripheral neuropathy, especially in the legs) or wet (characterized by edema because of dilated cardiomyopathy).
2. Wernicke-Korsakoff syndrome: In the United States, thiamine deficiency, which is seen primarily in association with chronic alcoholism, is due to dietary insufficiency or impaired intestinal absorption of the vitamin. Some individuals with alcoholism develop Wernicke-Korsakoff syndrome, a thiamine-deficiency state characterized by mental confusion, gait ataxia, nystagmus (a to-and-fro motion of the eyeballs), and ophthalmoplegia (weakness of eye muscles) with Wernicke encephalopathy as well as memory problems and hallucinations with Korsakoff dementia. The syndrome is treatable with thiamine supplementation, but recovery of memory is typically incomplete.
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