Thiamin diphosphate brain

Parkhomenko, Y.M., Kudryavtsev, P.A., Pylypchuk, Yu, S., Chekhivska, L.I., Stepanenko, S.P., Sergiichuk, A.A., and Bunik, V.I., 2011. Chronic alcoholism in rats induces a compensatory response, preserving brain thiamine diphosphate, but the 2-oxo- acid dehydrogenases are inactivated despite unchanged coenzyme. Journal of Neurochemistry. 117 1055 1065. 

Vitamin Bi, also called thiamine, is required for all tissues and high concentrations are found in skeletal muscle, heart, liver, kidneys and brain. Thiamine diphosphate (TDP) is the active form and it serves as a cofactor for several enzymes involved in carbohydrate catabolism. These enzymes are also important in the biosynthesis of many cellular constituents, including neurotransmitters, and for the production of reducing equivalents used in oxidant stress defenses (Ba 2008). Thiamine is considered an anti-stress vitamin because it strengthens the immune system and improves the body s ability to withstand stress conditions (Haas 1988). 

In the 1930s, Peters and co-workers showed that thiamine deficiency in pigeons resulted in the accumulation of lactate in the brainstem [ 15]. Furthermore, they showed that the addition of small quantities of crystalline thiamine to the isolated brainstem tissue from thiamine-deficient birds in vitro resulted in normalization of lactate levels. These findings led to the formulation of the concept of the biochemical lesion in thiamine deficiency. Subsequent studies showed that the enzyme defect responsible for the biochemical lesion was a-KGDH rather than pyruvate dehydrogenase (PHDC), as had previously been presumed. a-KGDH and PHDC are major thiamine diphosphate (TDP)-dependent enzymes involved in brain glucose oxidation (Fig. 34-4). 

The two transamination steps in the pathways may be linked, as indicated in Fig. 17-5, to form a complete cycle that parallels the citric acid cycle but in which 2-oxoglutarate is oxidized to succinate via glutamate and y-aminobutyrate. No thiamin diphosphate is required, but 2-oxoglutarate is reductively aminated to glutamate. The cycle is sometimes called the y-aminobutyrate shunt, and it plays a significant role in the overall oxidative processes of brain tissue. 

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... 

Fig. 2 Intercellular trafficking and thiamine and thiamine esters in brain. TMP thiamine monophosphate, TDP thiamine diphosphate, TTP thiamine triphosphate, TPKinase thiamine pyrophosphokinase...

Bettendorff, L., Mastrogiacomo, F., Wins, P., Kish, S.J., Grisar, T., and Ball, M.J., 1997. Low thiamine diphosphate levels in brains of patients with frontal lobe degeneration of the non-Alzheimer s type. Journal of Neurochemistry. 69 2005-2010. 

In brain, four major enzyme systems utilize thiamine in the form of thiamine diphosphate (TDP) as a major cofactor, i.e. a-ketoglutarate dehydrogenase complex (KGDHC), pyruvate dehydrogenase complex, branched-chain a-keto acid dehydrogenase complex (BCKDHQ and transketolase. 

Table 33.3 Thiamine diphosphate deficits reduce acetyl-CoA levels in sub-cellular compartments of the brain neurons, suppressing their viability and cholinergic neurotransmission. Data from Bielarczyk et al. (2005), Bizon-Zygmanska et al. (2011) and Jankowska-Kulawy et al. (2010) expressed as means SEM in pmol/mg protein ( = 5-20 experiments). Italics refer to fractions of acetyl-CoA and acetylcholine provided through the ATP itrate lyase pathway (see Figure 33.1). Bold numbers refer to nonviable cell fractions assayed by trypan blue exclusion assay and expressed as a percentage of the whole cell population.

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... 

The content of phosphorylated derivatives of thiamine has been investigated in a variety of tissues using Dowex-1 ion-exchange columns. The following proportions of thiamine and thiamine mono-, di-, and triphosphates were found in rat brain, heart, liver, and kidney thiamine 5%, monophosphate 10%, diphosphate 80%, and triphosphate 5%. The high levels of diphosphate are not surprising—diphosphate is the form in which the vitamin is active. But the presence of triphosphate remains unexplained because the role of triphosphate is not clear, and it has been suggested that triphosphate appears only when excessive amounts of thiamine are administered. 

---