Transport thiamin monophosphate

In brain, as in most mammalian cells, thiamine occurs predominantly in the form of TDP, the remainder being made up of thiamine monophosphate (10%), thiamine triphosphate (5-10%) and trace amounts of free thiamine. Thiamine is transported into brain and phosphory-lated by the action of thiamine pyrophosphokinase, and inhibition of this enzyme by thiamine antagonists such as pyrithiamine results in decrease synthesis of TDP. Treatment of experimental animals with pyrithiamine results in a generalized reduction of TDP concentrations and an early selective loss in activity of a-KGDH in regions... 

Some thiamin is phosphorylated to thiamin monophosphate in the intestinal mucosa, although this is not essential for uptake, and isolated membrane vesicles wUl accumulate free thiamin against a concentration gradient. Thiamin does not accumulate in the mucosal cells there is sodium-dependent active transport across the basolateral membrane, so that the mucosal concentration of thiamin is lower than that in the serosal fluid (Hindi et al., 1984 Hindi and Laforenza, 2000 Dudeja et al., 2001). 

Patrini C, Reggiani C, LaforenzaU, and Hindi G (1988) Blood-brain transport of thiamine monophosphate in the rat a kinetic study invivo. Journal of Neurochemistry 50,90-3. 

Reggiani C, Patrini C, and Hindi G (1984) Nervous tissue thiamine metabolism in vivo. 1. Transport of thiamine and thiamine monophosphate from plasma to different brain regions of the rat. Brain Research 293,319-27. 

The cofactor form of thiamin is thiamiri pyrophosphate (TPP). TPPis released from dietary proteins during hydrolysis in the gastrointestinal tract and then hydroly 2ed to thiamin- The thiamin is absorbed and transported into various tissues, where it Is converted back to TPP by the action of thiaminokinase (Figure 9.70). A small proportion of the body s thiamin occurs as thiamin monophosphate (TMP) and thiamin trisphosphate (TTP). 

Vitamin Bi is transported as free thiamine (T ), but the biochemically active forms are the phosophorylated derivatives, including thiamine monophosphate... 

Most dietary thiamin is present as phosphates, which are readily hydrolysed by intestinal phosphatases, and free thiamin is readily absorbed in the duodenum and proximal jejunum and then transferred to the portal circulation as free thiamin or thiamin monophosphate. This is an active transport process, and is inhibited by alcohol, which may explain why alcoholics are especially susceptible to thiamin deficiency. 

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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