Energy metabolism thiamin deficiency

Water-Soluble Vitamins. Vitamin G (ascorbic acid) functions in the formation of collagen, wound healing, metabolic functions, and other roles. Foods high in vitamin G include citrus fruits, strawberries, cantaloupe, and cruciferous vegetables. B vitamins are important in energy metabolism. Thiamin (Bj) is called the antineuritic vitamin. Riboflavin (B ), rarely deficient in the diet, is found most abundantly in milk and dairy products. Niacin (Bj) is prevalent in meats, poultry, fish, peanut butter, and other foods. Other major B vitamins include folic acid (B ), B, and Bj2-... 

Pannunzio, P., Hazell, A. S., Pannunzio, M., Rama Rao, K. V. and Butterworth, R. F. Thiamine deficiency results in metabolic acidosis and energy failure in cerebellar granule cells an in vitro model for the study of cell death mechanisms in Wernicke s encephalopathy. /. Neurosci. Res. 62 286-292, 2000. 

Pyruvate dehydrogenase plays an important role in energy metabolism to provide ATP, utilizing thiamine pyrophosphate as a cofactor in the reaction. In thiamine deficiency, the activity of pyruvate dehydrogenase is decreased, impairing the formation of ATP. The answer is (E). 

With such an extensive knowledge base, what is the present state of our understanding of the mechanisms of this disorder Not unexpectedly, initial studies, primarily in experimental animal models, focused on the known metabolic pathways which involve thiamine. Indeed, the classical studies of Peters in 1930 (Peters, 1969) showed lactate accumulation in the brainstem of thiamine deficient birds with normalization of this in vitro when thiamine was added to the tissue. This led to the concept of the biochemical lesion of the brain in thiamine deficiency. The enzymes which depend on thiamine are shown in Fig. 14.1. They are transketolase, pyruvate and a-ketoglutarate dehydrogenase. Transketolase is involved in the pentose phosphate pathway needed to form nucleic acids and membrane lipids, including myelin. The ketoacid dehydrogenases are key enzymes of the Krebs cycle needed for energy (ATP) synthesis and also to form acetylcholine via Acetyl CoA synthesis. Decrease in activity of this cycle would result in anaerobic metabolism and lead to lactate formation (i.e., tissue acidosis) (Fig. 14.1). 

McCandless, D.W. (1982). Energy metabolism in the lateral vestibular nucleus in pryithiamin-induced thiamin deficiency. Ann. N.Y. Acad. Sci. 378 355-364. 

McCandless, D.W. and Schwartzenburg, F.C., Jr. (1981). The effect of thiamine deficiency on energy metabolism in cells of the lateral vestibular nucleus. Res. Comm. Psychol. Psychiat. Behav. 6 183-190. 

Nerve tissue is mainly dependent for ATP production on glucose metabolism via glycolysis to produce acetyl CoA by the PDH reaction for oxidation in Krebs cycle. Since thiamin is essential for PDH activity, thiamin deficiency, which can occur in malnourished alcoholics, results in PDH dysfunction and an energy deficit in nerve tissue. This causes hyperlactataemia and neuropathy, which can progress to Wernicke s encephalopathy and Korsakoff s psychosis (Chapter 53). 

An explanation for the pathogenesis of the lesions observed in thiamine deficiency would seem to follow logically from these biochemical observations, for in the thiamine-deficient animal, at least two enzymes involved in the Krebs cycle are blocked. The block of pyruvic decarboxylase prevents the entry of the products of glycolysis into the Krebs cycle. The block of a-ketoglutarate decarboxylase restricts the oxidation of both carbohydrates and fatty acids. A severe metabolic distortion follows, and one of the main manifestations of the distortion is a reduction of the amount of chemical energy available in the form of ATP. Clearly, those organs that suffer the most from such alterations are those that are metabolically most active, and the heart and the peripheral nervous system surely qualify as such. 

ThDP plays a crucial role as coenzyme for several enzymes and enzyme complexes such as transketolase (EC 2.2.1.1) and the enzyme complexes pyruvate (EC 1.2.4.1) and 2-oxoglutarate (EC 1.2.4.2) dehydrogenases, present in nearly all organisms. They play important catabolic roles and are key actors in cell energy metabolism (Figure 5.1). Reduced activity of these enzymes as a consequence of thiamin deficiency results in decreased glucose oxidation. As the brain heavily relies on oxidative metabolism, it is more severely affected by thiamin deficiency than other organs. 

Thiamine deficiency results in mitochondrial dysfunction in which compromised brain energy metabolism produces oxidative stress, exci-totoxicity and inflammatory responses leading to neuronal cell death. 

Figure 32.2 Effect of thiamine deficiency on mitochondrial energy metabolism illustrated with a scatter plot of relative expression from mitochondrial energy metabolism gene array. Array analysis shows Group 1 (thiamine deficiency) versus control (pair-fed control) expression in which numerous genes are downregulated (gray circles). In general, thiamine deficiency decreased the expression of many genes of the mitochondrial metabolic pathway.

In the pigeon, opisthotonos is the major neurological symptom of thiamine deficiency. Pyruvate utilization is impaired by lack of cocarboxylase ( = thiamine pyrophosphate). Oxygen consumption of nerve cells decreases since these cells obtain the greatest part of their energy from carbohydrate metabolism. Pyruvate accumulates in the tissues. In a few minutes, after addition of thiamine to the systems in vitro, the O2 consumption increases. Similarly the opisthotonos disappears 1 hr after intracerebral injection of thiamine. 

Thiamin or Bj has been recognized historically as the main cause of beriberi. Thiamin exists in free and bound forms (thiamin diphosphate and the protein-phosphate-thiamin complex). The bound forms are split in the gastrointestinal tract. The absorbed thiamin acts as a coenzyme in energy metabolism, mainly in the conversion of glncose to fats. In addition, it has high implications in the functioning of peripheral nerves (nerve impulses), brain, and muscles. Thiamin deficiency causes... 

Severe thiamine vitamin Bf) deficiency results in beriberi. The symptoms can include growth retardation, muscular weakness, apathy, edema, and heart failure. Neurological symptoms, such as personality changes and mental deterioration, also may be present in severe cases. Because of the role played by thiamine in metabolic processes in all cells, a mild deficiency may occur when energy needs are increased. Since thiamine is widely distributed in food, beriberi is rare except in communities existing on a single staple cereal food. The disease does occur with some frequency in alcoholics, whose poor diet may lead to an inadequate daily intake of thiamine. 

Carbohydrate metabolism provides the main energy source in coccidia. Diets deficient in thiamin, riboflavin, or nicotinic acid—all cofactors in carbohydrate metabolism—result in suppression of parasitic infestation of chickens by E tenella and E acervulina. A thiamin analog, amprolium—1-[(4-amino-2-propyl-5-pyrimidinyl)-methyl]-2-picolinium chloride—has long been used as an effective anticoccidial agent in chickens and cattle with relatively low host toxicity. The antiparasitic activity of amprolium is reversible by thiamin and is recognized to involve inhibition of thiamin transport in the parasite. Unfortunately, amprolium has a rather narrow spectrum of antiparasitic activity it has poor activity against toxoplasmosis, a closely related parasitic infection. 

The population thought to be nxost at risk for Bf, deficiency comprises chronic alcoholics. The deficiency arises fixim a low intakt of the vitamin as well as from alcoho[-induced impairments in the metabolism of the vitamin. An alcoholic deriving of his or her energy requirement from whiskey might be expected to be consuming only 20% of the KDA for vitamin 8, as well as for other nutrients such as protein, folate, and thiamin. 1 he symptoms of deficiency are not specific for this nutrient- They include depression, confusion, and sometimes convulsions. 

Thiamin transporter Carbohydrate metabolism is the primary energy source in coc-cidia. Inhibition of the cellular transport of thiamin by the structurally similar agent ampro-lium leads to a deficiency of this cofactor in coccidia. 

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