Muscles thiamin triphosphate

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 ... 

Phosphorylation by ADP, catalyzed by adenylate kinase - this enzyme is especially important in the rapid synthesis and turnover of thiamin triphosphate in slow-twitch white muscle fibers. 

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 triphosphate is formed in brain and skeletal muscle by phosphorylation of thiamin diphosphate (Section 6.2), and its concentration is very precisely controlled, because there is also an active thiamin triphosphatase (Lakaye et al., 2002). In nervous tissue thiamin triphosphate is localized... 

Miyamoto T, Kakizawa T, and Hashizume K (1999) Inhibition of nuclear receptor signalling by poly(ADP-ribose) polymerase. Molecular and Cell Biology 19,2644-9. Miyoshi K, Egi Y, Shioda T, and Kawasaki T (1990) Evidence for in vivo synthesis of thiamin triphosphate by cytosolic adenylate kinase in chicken skeletal muscle./oMrnal... 

The cardiomyopathy is directly related to a reduction in the normal biochemical function of the vitamin thiamine in heart muscle. Inhibition of the a-keto acid dehydrogenase complexes causes accumulation of a-keto acids in heart muscle (and in blood), resulting in a chemically-induced cardiomyopathy. Impairment of two other functions of thiamine may also contribute to the cardiomyopathy. Thiamine pyrophosphate serves as the coenzyme for transketolase in the pentose phosphate pathway, and pentose phosphates accumulate in thiamine deficiency. In addition, thiamine triphosphate (a different coenzyme form) may function in Na conductance channels. 

The structures of the phosphate esters of thiamine are also shown in Figure 1. Thiamine monophosphate (TMP), thiamine pyrophosphate (TPP), and thiamine triphosphate (TTP) are commonly found in organisms. About 80% to 90% of the total thiamine content in cells is TPP, the coenzyme form of thiamine. In some animal tissues, especially pig skeletal muscle (2) and chicken white skeletal muscle (3), TTP is present in an extremely high amount (70% to 80% of total thiamine—i.e., thiamine plus thiamine phosphate esters). However, TTP has no coenzyme activity. Thiamine pyrophosphate in the dried state is stable for several months when stored at a low temperature in the dark. In solution, TPP is unstable and partially decomposes to TMP and/or thiamine when stored for several months at pH 5 and 38°C. However, TPP in solution at pH 2 to 6 and at 0°C is... 

Y Egi, S Koyama, H Shikata, K Yamada, T Kawasaki. Content of thiamin phosphate esters in mammalian tissues—an extremely high concentration of thiamin triphosphate in pig skeletal muscle. Biochem Int 12 385-390, 1986. 

Thiamin is the least stored of all the vitamins. The adult human body contains approximately 30 mg. Of the thiamin stored in the body, about 80% is thiamin pyrophosphate, about 10% is thiamin triphosphate, and the remainder is thiamin monophosphate. The liver, kidneys, heart, brain, and skeletal muscles have somewhat higher concentrations than the blood. If the diet is deficient, tissues are depleted of their normal content of the vitamin ini to 2 weeks, so fresh supplies are needed regularly to provide for maintenance of tissue levels. Body tissues take up only as much thiamin as they need with the need increased by metabolic demand (fever, increased muscular activity, pregnancy, and lactation) or by composition of the diet (carbohydrate increases the need for thiamin, while fat and protein spare thiamin). Because thiamin is water soluble, most of the vitamin not required for day-to-day use is excreted in the urine. This means that the body needs a regular supply, and that unneeded intakes are wasted. With a well-balanced diet, approximately 0.1 mg is normally excreted every 24 hours. However, the amount excreted in the urine decreases as the intake becomes inadequate and increases as the intake exceeds body needs because of this, the most widely used biochemical method to assess thiamin status in individuals is the measurement of the vitamin in the urine. 

Thiamine absorption occurs primarily in the proximal small intestine by both a saturable (thiamine transporter) process at low concentration (Ipmol/L, or lower) and by simple passive diffusion beyond that, though percentage absorption diminishes with increased dose. The absorbed thiamine undergoes intracellular phosphorylation, mainly to the pyrophosphate, but at the serosal side 90% of the transferred thiamine is in the firee form. Thiamine uptake is enhanced by thiamine deficiency and reduced by thyroid hormone, diabetes, and ethanol ingestion. The gene for the specific thiamine transporter has been identified, and the transporter cloned. Thiamine is carried by the portal blood to the liver. The firee vitamin occurs in the plasma, but the coenzyme, TPP, is the primary cellular component. Approximately 30 mg is stored in the body with 80% as the pyrophosphate, 10% as triphosphate, and the rest as thiamine and its monophosphate. About half of the body stores are found in skeletal muscles, with much of the remainder in heart, liver, kidneys, and nervous tissues (including the brain, which contains most of the triphosphate). 

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