Metabolic functions of thiamin Domina Petric, MD

Cocarboxylase The metabolically functional form of thiamin is its diphosphate ester, thiamin pyrophosphate (TPP), also called cocarboxylase. Several enzymes use TPP as an essential cofactor for the cleavage of the C–C bond of α-keto acids (pyruvate) to yield products subsequently transferred to an acceptor. November 12, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Cocarboxylase TPP serves as a classic coenzyme, binding covalently to the holoenzyme by apoenzymic recognition of both the substituted pyrimidyl and thiazole moieties. Each TPP-dependent enzyme also requires Mg2+ or some other divalent cation for activity. November 12, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Cocarboxylase The general mechanism of the coenzyme action of TPP involves its deprotonation to form a carbanion at C-2 of the thiazole ring, which reacts with the polarized 2-carbonyl group of the substrate (an α-keto acid or α-keto sugar) to form a covalent bond. November 12, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

α-keto acid dehydrogenases TPP functions in the oxidative decarboxylation of α-keto acids by serving as an essential cofactor in multienzyme α-keto acid dehydrogenase complexes. November 12, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

TPP-dependent enzyme classes are: Pyruvate dehydrogenase, converting pyruvate to acetyl-CoA. α-ketoglutaric dehydrogenase converting α-ketoglutarate to succinyl-CoA. Branched-chain α-keto acid dehydrogenase, converting branched-chain α-keto acids to the corresponding acyl-CoAs. November 12, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Maple syrup urine disease Emaze.com A rare (1 per 100,000 births) genetic defect in the TPP enzyme branched-chain keto acid dehydrogenase. The disorder is manifested in infancy as lethargy, seizures and mental retardation. It can be detected by the maple syrup odor of the urine, resulting from the presence of the keto acid leucine. Some cases respond to high doses (10-200 mg/day) of thiamin. November 12, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Transketolase Thiamin functions in the form of TPP as an essential cofactor for transketolase. Transketolase catalyzes the cleavage of a C-C bond in α-keto sugars transferring the resulting 2-C fragment (active glycoaldehyde) to an aldolase acceptor. α-keto sugars are xylulose 5-phosphate, sedoheptulose 7-phosphate, fructose 6-phosphate, d-xylulose and d-fructose. November 12, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Transketolase Transketolase functions at two steps in the hexose monophosphate shunt for the oxidation of glucose. Transketolase is found in the cytosol of many tissues, particularly liver blood cells that rely on carbohydrate metabolism. November 12, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Role of thiamin in nervous function That thiamin is required by nervous tissue is evidenced by the localization of signs of thiamin deprivation, which are mainly neurologic. Thiamin has a catalytic activity in the mechanism of Na+ permeability. Thiamin, probably as TPP, is involved in maintaining the fixed negative charge on the inner surface of the membrane. November 12, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Other Thiamin deficiency has been implicated in cases of sleep apnea as well as in sudden infant death syndrome (SIDS). November 12, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Literature Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. November 12, 2018