Disease relevance of thiamine diphosphate

• Effect of cocarboxylase in dogs subjected to experimental septic shock [1].
• Beneficial effects of cocarboxylase in the treatment of experimental myocardial infarction in dogs [2].
• The conclusions are that severe cirrhosis does not affect the erythrocyte transketolase apoenzyme, the ability of the tissues to convert thiamine to thiaminepyrophosphate for use in the erythrocytes or the absorption of thiamine from the gastrointestinal tract [3].
• Pseudomonas fluorescens is able to grow on R-benzoin as the sole carbon and energy source because it harbours the enzyme benzaldehyde lyase that cleaves the acyloin linkage using thiamine diphosphate (ThDP) as a cofactor [4].

High impact information on thiamine diphosphate

• It contains thiamine pyrophosphate (TPP) and at least two ferredoxin-type [4Fe-4S] clusters per molecule, as determined by iron analysis and EPR spectroscopy [5].
• Each catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA and CO2 near the optimal growth temperature of the organism and are virtually inactive at 25 degrees C. Both PORs contain a thiamine pyrophosphate (TPP) cofactor and at least two [4Fe-4S] ferredoxin-type clusters [6].
• Bromopyruvate also inactivates the intact pyruvate dehydrogenase complex in a TPP-dependent process, but the inhibition is more rapid and is mechanistically different [7].
• Phosphorylation also substantially inhibited the transfer of [14C]acetyl groups from enzyme-bound [14C]acetylhydrolipoate to TPP in the presence of NADH [8].
• Circular dichroism spectra were used to monitor the effect of phosphorylation on the following stages of the process: holoform formation from apo-E1 and thiamine pyrophosphate (TPP), substrate binding and active site deacetylation [9].

Biological context of thiamine diphosphate

• Cocarboxylase inhibited deterioration in metabolic function as reflected by improved pH and base excess as well as maintenance of normal oxygen consumption [1].
• Our analysis helps to further define the THI regulon and hence the spectrum of genes/proteins involved in the ThDP homeostasis [10].

Anatomical context of thiamine diphosphate

• METHODS: Measurement of erythrocyte transketolase activity (ETK) and thiaminpyrophosphate (TPP) effect in 55 consecutive HIV-positive patients of a specialized outpatient clinic were grouped into five groups according to their CD4 counts [11].
• In conclusion, this experiment suggests that cocarboxylase may be beneficial to ischemic canine myocardium by virtue of its favorable systemic hemodynamic effects [2].
• During the reanimation the addition of ATP to the blood stimulated the restoration of RNA biosynthesis in the spinal cord to a considerable extent; the addition of cocarboxylase to the blood promoted cardiac RNA biosynthesis as well as cardiac and pancreatic DNA biosynthesis during recovery [12].
• In particular, we identify novel proteins putatively involved in thiamine and/or ThDP transport across the plasma and the mitochondrial membrane [10].
• Cocarboxylase, a radioprotector, improved these changes regarding the structures of the small intestine and also the GP of sublingual glands, stomach, small intestine and colon, demonstrating there its efficiency [13].

Associations of thiamine diphosphate with other chemical compounds

• It has been shown that phosphorylation of E1 reduces its affinity for TPP and prevents holo-E1 interaction with pyruvate [9].
• PD patients under levodopa therapy had significantly higher CSF thiaminediphosphate and total thiamine than those not treated with this drug [14].

Gene context of thiamine diphosphate

• The increase in the liver transketolase activity by the in vitro addition of cocarboxylase (TPP effect) was higher in group 3 than in group 4 although original transketolase activity was lower in group 4 [15].
• The change in the energy barriers for the heterogeneous reduction of pyruvate decarboxylase (PDC) relative to its coenzyme, thiamin pyrophosphate (ThPP), was determined experimentally using square wave voltammetry (SWV) to be 5.3 kcal/mol [16].

Analytical, diagnostic and therapeutic context of thiamine diphosphate

• Cysteine-cystine and IVX but not cocarboxylase supplementation allowed H. somnus to grow in Eagle minimal medium, a completely synthetic medium, but attempts at serial passage were unsuccessful [17].
• In one group (Group II), cocarboxylase (150 mgm/kg) was given systematically via a central line 15 minutes and 45 minutes after ligation, while in Group I an equal amount of D5W was given [2].

References