Nervous system thiamin

On the basis of depletion/repletion studies, an intake ofO.2 mgper 1,000kcal is required to maintain normal urinary excretion, but an intake of 0.3 mg per 1,000 kcal is required for a normal transketolase activation coefficient. At low levels of energy intake, there will be a requirement for metabolism of endogenous substrates and to maintain nervous system thiamin triphosphate. 

Thiamine, whose structure is shown in Figure 18.17, is known as vitamin Bj and is essential for the prevention of beriberi, a nervous system disease that has occurred in the Far East for centuries and has resulted in considerable sickness and death in these countries. (As recently as 1958, it was the fourth leading cause of death in the Philippine Islands.) It was shown in 1882 by the director-general of the medical department of the Japanese nayt that beriberi could be prevented by dietary modifications. Ten years later, Christiaan Eijkman, a Dutch medical scientist working in Java, began research that eventually showed that thiamine was the... 

B, Thiamin Coenzyme in pyruvate and a-ketoglutarate, dehydrogenases, and transketolase poorly defined function in nerve conduction Peripheral nerve damage (beriberi) or central nervous system lesions (Wernicke-Korsakoff syndrome)... 

Thiamin Deficiency Affects the Nervous System Heart... 

Straightforward thiamine deficiency in man, beri-beri, is characterized by accumulation of pyruvic and lactic acids in the blood and brain, and impairment of cardiovascular, nervous, and gastrointestinal function (DIO, G17, P4, Yl). Neurological lesions characterize thiamine deficiency in growing rats (B40), guinea pigs (M6), mice (M13), chicks, and pigeons (B30). The effects of thiamine deficiency on the central nervous system of animals have been reviewed (DIO). 

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.]... 

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. 

The peripheral nervous system disease, beriberi, caused by thiamin deficiency, has been known sporadically for nearly 1,300 years it became a major problem of public health in the Far East in the nineteenth century with the introduction of the steam-powered rice mUl, which resulted in more widespread consumption of highly milled (polished) rice. Thiamin was discovered as the factor in the discarded polishings that protected against the disease. 

Although now largely eradicated, beriberi remains a problem in some parts of the world among people whose diet is especially high in carbohydrates. A different condition, affecting the central rather than peripheral nervous system, the Wemicke-Korsakoff syndrome, is also due to thiamin deficiency. It occurs in developed countries, especially among alcoholics and narcotic addicts. 

Thiamin was the first of the vitamins to be demonstrated to have a clearly defined metabolic function as a coenzyme indeed, the studies of Peters group in the 1920s and 1930s laid the foundations not only of nutritional biochemistry but also of modern metabolic biochemistry and neurochemistry. Despite this, the mechanism by which thiamin deficiency results in central and peripheral nervous system lesions remains unclear in addition to its established coenzyme role, thiamin regulates the activity of a chloride transporter in nerve cells. 

Both thiamin monophosphate and free thiamin are found in cerebrospinal fluid. Uptake of thiamin monophosphate into cells in the central nervous system involves extracellular hydrolysis to free thiamin, probably catalyzed... 

Two percent to 3% of the thiamin in nervous tissue is present as the triphosphate, which also occurs in significant amounts in skeletal muscle, especially in fast-twitch muscle fibers. In the nervous system, the triphosphate is found exclusively in the membrane fraction muscle thiamin triphosphate is mainly cytosoUc. There are two pathways for formation of thiamin triphosphate from the diphosphate ... 

In both muscle and the central nervous system, there is an active thiamin triphosphatase, so that tissue concentrations of thiamin triphosphate are strictly regulated (Nishino et al., 1983 Miyoshi et al., 1990 Lakaye et al., 2002). 

Thiamin-Responsive Pyruvate Dehydrogenase Deficiency Genetic deficiency of pyruvate dehydrogenase Ela (which is on the X chromosome) leads to potentially fatal lactic acidosis, with psychomotor retardation, central nervous system damage, atrophy of muscle fibers and ataxia, and developmental delay. At least some cases respond to the administration of high doses (20 to 3,000 mg per day) of thiamin. In those cases where the enzyme has been studied, there is a considerable increase in the of the enzyme for thiamin diphosphate. Female carriers of this X-linked disease are affected to a variable extent, depending on the X-chromosome inactivation pattern in different tissues (Robinson et al., 1996). 

Early studies showed that the development of neurological abnormalities in thiamin deficiency did not follow the same time course as the impairment of pyruvate and 2-oxoglutarate dehydrogenase or transketolase activities. The brain regions in which metabolic disturbances are most marked were not those that are vulnerable to anatomical lesions. These studies suggested a function for thiamin in the nervous system other than its coenzyme role. 

In addition, other possible causes of dementia also need to be excluded, especially the treatable forms of cognitive impairment, such as that due to depression, chronic drug intoxication, chronic central nervous system infection, thyroid disease, vitamin deficiencies (i.e.. Bn and thiamine), central nervous system angitis, and normal-pressure hydrocephalus (Bird, 2008). Individuals who do not meet these criteria but have short-term memory loss and have only minimal impairment in other cognitive abilities and are not functionally impaired at work or at home are considered to have mild cognitive impairment (Petersen et al., 2001). 

The importance of thiamine is evident in that it is a vitamin, an essential substance that must be provided in the diet to prevent beriberi, a nervous system disease. 

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