Thiamine pyrophosphate deficiency

Water-Soluble Vitamins Thiamine (B,) Precursor of the coenzyme thiamine pyrophosphate. Deficiency can cause beriberi. 

Vitamin Bi, or thiamine, is a precursor to thiamine pyrophosphate, an essential coenzyme for several enzymes. Beriberi is a vitamin Bi deficiency disease. 

Vitamin deficiency of Bj leads to the disease known as Beriberi. However, nowadays in the Western hemisphere, vitamin Bj deficiency is mainly found as a consequence of extreme alcoholism. In fact, the vitamin absorption by the gut is decreased and its excretion is increased by alcohol. Alcohol also inhibits the activation of vitamin Bj to its coenzyme form, thiamine pyrophosphate ester (TPP). There is no evidence of adverse effects of oral intake of thiamine [417]. The main food sources of vitamin Bj are lean pork, legumes, and cereal grains (germ fraction). It is soluble in water and stable at higher temperature and at pH lower than 5.0, but it is destroyed rapidly by boiling at pH 7.0 or above. 

Dietary deficiency of thiamine (vitamin 6,j results In an Inability to synthesize thiamine pyrophosphate, and the pathophysiology arises from Impaired glucose utilization, especially manifested In the nervous system. 

Coenzymes The pyruvate dehydrogenase complex contains five coenzymes that act as carriers or oxidants for the intermediates of the reactions shown in Figure 9.3. Ei requires thiamine pyrophosphate, Ep requires lipoic acid and coenzyme A, and E3 requires FAD and NAD+. [Note Deficiencies of thiamine or niacin can cause serious central nervous system problems. This is because brain cells are unable to produce sufficient ATP (via the TCA cycle) for proper function if pyruvate dehydrogenase is inactive.]... 

Vitamin B1 (thiamine) has the active form, thiamine pyrophosphate. It is a cofactor of enzymes catalyzing the conversion of pyruvate to acetyl CoA, a-ketoglutarate to succinyl CoA, and the transketolase reactions in the pentose phosphate pathway. A deficiency of thiamine causes beriberi, with symptoms of tachycardia, vomiting, and convulsions. In Wernicke-Korsakoff syndrome (most common in alcoholics), individuals suffer from apa thy, loss of memory, and eye movements. There is no known toxicity for this vitamin. 

Nearly all the water-soluble vitamins are heterocyclic compounds. Among the first to be isolated was thiamine (vitamin Bi) (62), deficiency of which causes degenerative changes in the nervous system, including the multiple peripheral neuritis characteristic of beriberi. Thiamine deficiency can arise from decomposition of the vitamin by bacteria in the gut. In mammalian metabolism the hydroxy group of thiamine is esterified to give cocarboxylase (thiamine pyrophosphate) which catalyzes the decarboxylation of a-keto acids to aldehydes, acyloins or acids, and their transformation into acyl phosphates. 

Diseases and disorders resulting from a deficiency of thiamine include beriben, opisthotonos (in birds), polyneuritis, hyperesthesia, bradycardia, and edema. Rather than a specific disease, beriberi may be described as a clinical state resulting from a thiamine deficiency. In body cells, thiamine pyrophosphate is required for removing carbon dioxide from various substances, including pyruvic acid. Actually, this is accomplished by a decarboxylase of which thiamine pyrophosphate is a part. Where... 

Thiamin is important as a component of the coenzyme thiamin pyrophosphate (TPP) (cocarboxylase). Good sources are lucerne, grains and yeast. A deficiency is less frequently encountered than deficiencies of other vitamins, since thiamin occurs in abundance in whole grains which make up the major part of poultry diets. A diet deficient in thiamin results in nervous disorders in both young and old birds, and eventual paralysis of the peripheral nerves (polyneuritis). 

Answer Thiamine is required for the synthesis of thiamin pyrophosphate (TPP), a prosthetic group in the pyruvate dehydrogenase and a-ketoglutarate dehydrogenase complexes. A thiamin deficiency reduces the activity of these enzyme complexes and causes the observed accumulation of precursors. 

Pekovich SR, Martin PR, and Singleton CK (1996) Thiamine pyrophosphate-requiring enzymes are altered during pyrithiamine-induced thiamine deficiency in cultured human lymphoblasts./oMma/o/AiMfrihow 126,1791-8. 

Vitamin Bj Vitamin Bj was discovered in 1926 by Jansen and Do-NATH, who synthesized it in its crystalline form from rice bran. It was initially called aneurine due to its antipolyneuropathic effect. Because it contains sulphur, Windaus correctly renamed it thiamine in 1932, a term by which it is still known today. The stixicture of this vitamin was described by Williams and Grewe in 1936. It is made up of pyrimidine and thiazole. Thiamine occurs in nature as free thiamine and in the form of thiamine monophosphate, diphosphate and triphosphate. A maximum amount of 8 — 15 mg is absorbed daily in the proximal portion of the small intestine. In the case of oversupply, thiamine is neither stored nor intestinally absorbed. A regular intake, with a daily requirement of about 1 mg, is necessary. The major coenzyme is thiamine pyrophosphate (TPP). Thiamine deficiency may be caused by malnutrition, impaired absorption, alcoholism, antithiamines or a lack of magnesium. Magnesium is an important cofactor for the coenzyme thiamine pyrophosphate. 

Branched-chain ketoaciduria (commonly known as Maple Syrup Urine Disease MSUD) is another ailment that may be caused by thiamine deficiency. In MSUD, the oxidative decarboxylation of alpha-keto acids derived from, i.e. valine, isoleucine, and leucine, is blocked due to an inadequate supply of the coenzyme thiamine pyrophosphate (TPP). Clinical symptoms of MSUD include mental and physical retardation. Describe briefly the structure of Riboflavin (Vitamin B-2) and its biochemical role. 

Oxythiamine and neopyrithiaminc arc aniivilamins used in the study of the deficiency state. Oxythiamine is a competitive inhibitor of thiamine pyrophosphate. Neopyrithiamine inhibits the pyrophosphotylation of thiamine. 

The transketolase activation test is in reality two tests one a measurement of basal activity and the other the degree to which the basal activity can be increased by exogenous thiamine pyrophosphate, and each may be influenced by different factors. There is evidence that chronic deficiency states of thiamine may down regulate synthesis of the apoen-zyme. In comparison studies against erythrocyte TPP concentrations, better correlations were obtained with basal activity rather than the activation coefficient. ... 

Naito E, Ito M, Yokota I, Saijo T, Matsuda J, Ogawa Y et al. Thiamine-responsive pyruvate dehydrogenase deficiency in two patients caused by a point mutation (F205L and L216F) within the thiamine pyrophosphate binding region. Biochim Biophys Acta 2002 1588 79-84. 

D. This patient has exhibited symptoms of beri beri heart disease, which is a result of a nutritional deficiency in vitamin Bj (thiamine). The active form of the vitamin, thiamine pyrophosphate, is a required cofactor for a-ketoglutarate dehydrogenase. 

Long term usage of ethanol enhances the metabolic removal of vitamin B. (thiamin pyrophosphate). B deficiencies are known to result in polyneuritis, a neurological disorder, and beriberi, a cardiac problem. 

Under aerobic conditions pyruvate is converted to acetyl CoA. The coenzymes NAD+, FAD, thiamine pyrophosphate, and coenzyme A are required by the pyruvate dehydrogenase complex for the conversion of pyruvate to acetyl CoA. These coenzymes are synthesized from the vitamins niacin, riboflavin, thiamine, and pantothenic acid, respectively. If the vitamins are not available, the coenzymes will not be available and pyruvate cannot be converted to acetyl CoA. Because the complete oxidation of the acetyl group of acetyl CoA produces the vast majority of the ATP for the body, ATP production would be severely inhibited by a deficiency of any of these vitamins. 

Elderly people living on their own frequently have an inadequate diet. This is particularly true of men if they are unused to cooking for themselves. This patient may have a number of micronutrient deficiencies but, acutely, the most important would be possible thiamine deficiency. This can be detected by demonstrating an increase in the percentage activation of erythrocyte transketolase in vitro by the addition of thiamine or the measurement of thiamine pyrophosphate in erythrocytes. 

Thiamin is also known as vitamin Bj. In the body it is converted to thiamin pyrophosphate (TPP), an essential coenzyme serving enzymes involved in the breakdown of nutrient molecules for energy. Thiamin deficiency in its severest form causes beriberi. 

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