Disease relevance of Tkt

• In retinas of diabetic animals, benfotiamine treatment inhibited these three pathways and NF-kappaB activation by activating transketolase, and also prevented experimental diabetic retinopathy [1].
• Replication-defective, amphotrophic retroviruses were constructed containing a chimeric varicella-zoster virus thymidine kinase (VZV TK) gene that is transcriptionally regulated by either the hepatoma-associated alpha-fetoprotein or liver-associated albumin transcriptional regulatory sequences [2].
• 2. For the transketolase substrates, ribose 5-phosphate and xylulose 5-phosphate, the apparent Km values were 0.3 and 0.5 mM, respectively, in both liver and hepatoma [3].
• The deficiency developed after 3 to 4 weeks and was evidenced by anorexia, weight-loss, and a significant increase in the erythrocyte transketolase activity ratio [4].
• A rat brain tumor model was used to test the herpes simplex virus (HSV)-thymidine kinase (TK) gene for its ability to selectively kill C6 and 9L tumor cells in the brain following systemic administration of the nucleoside analog ganciclovir [5].

Psychiatry related information on Tkt

• Transketolase is a key enzyme in the pentose-phosphate pathway which has been implicated in the latent human genetic disease, Wernicke-Korsakoff syndrome [6].
• Cultured fibroblasts from patients affected by Alzheimer's disease (AD) exhibited peculiar alterations of the enzyme transketolase (TK) [7].

High impact information on Tkt

• We have discovered that the lipid-soluble thiamine derivative benfotiamine can inhibit these three pathways, as well as hyperglycemia-associated NF-kappaB activation, by activating the pentose phosphate pathway enzyme transketolase, which converts glyceraldehyde-3-phosphate and fructose-6-phosphate into pentose-5-phosphates and other sugars [1].
• VZV TK metabolically activated the nontoxic prodrug 6-methoxypurine arabinonucleoside (araM), ultimately leading to the formation of the cytotoxic anabolite adenine arabinonucleoside triphosphate (araATP) [2].
• From the distribution of label at glucose carbons not labeled via the major pathway and from the carbon spin-spin splitting patterns observed, we conclude that transketolase is reversible whereas transaldolase is essentially irreversible in the nonoxidative pentose branch [8].
• The kinetic properties of transaldolase and transketolase were similar in normal liver and in rapidly growing hepatoma 3924A [3].
• Transketolase activity was highest in kidney (155%) and lowest in heart (26%) and skeletal muscle (23%) [3].

Chemical compound and disease context of Tkt

• MATERIAL AND METHODS: Pre-established macroscopic tumours in BDIX rats were treated by intraperitoneal injections of retrovirus producing cells (FLYA13 TK, FLYA13 granulocyte macrophage-colony stimulating factor (GM-CSF), FLYA13 interleukin 12 (IL-12)) and ganciclovir (GCV) [9].
• To estimate the nutritional and the pathological states in thiamin-deficiency-related diseases, especially Wernicke-Korsakoff syndrome, we studied the relationship among transketolase activity, transketolase concentration, and thiamin phosphate esters in rats chronically fed alcohol [10].
• We have previously demonstrated that human T-lymphotropic virus type I (HTLV-I) tax-expressing human T cell lines are selectively eliminated in the presence of aciclovir, using a retroviral vector carrying the herpes simplex virus thymidine kinase (HSV TK) gene under the control of the long terminal repeat (LTR) of HTLV-I [11].

Biological context of Tkt

• Here we report the cloning and partial characterisation of the coding sequences encoding human transketolase from a human brain cDNA library [6].
• Nucleotide and predicted amino acid sequence of a cDNA clone encoding part of human transketolase [6].
• Erythrocyte transketolase is more sensitive than leukocyte pyruvate decarboxylation rate to early thiamin deficiency in rats [12].
• The heterogeneous distribution of TK may reflect a variety of metabolic activities among different brain regions but does not provide a simple molecular explanation for selective cell death in either thiamine deficiency or other conditions where TK is reduced [13].
• A mechanism was proposed that involves a redox reaction between the nitroso substrate and the enzymatic intermediate "active glycolaldehyde" at the active-site of transketolase [14].

Anatomical context of Tkt

• In contrast, the TPP effect on erythrocyte transketolase activity was significantly increased after only 7 days of thiamin deficiency [12].
• The ability to phenotypically rescue a mutant (Rat-3, thymidine kinase-deficient) cell line by electroporation of functional TK enzyme has been investigated [15].
• Cysteine proteinases are responsible for characteristic transketolase alterations in Alzheimer fibroblasts [7].
• Lower expression of TK mRNA and protein occurred in layer V of cortex, olfactory tubercle, ventral pallidum, medial septal nucleus, hippocampus, thalamic and hypothalamic nuclei, mammillary body, central gray, and the substantia nigra [13].
• TK immunoreactivity also occurred in the nuclei of ubiquitously distributed glial cells, as well as ependymal cells [13].

Associations of Tkt with chemical compounds

• High-dose thiamine and benfotiamine therapy increased transketolase expression in renal glomeruli, increased the conversion of triosephosphates to ribose-5-phosphate, and strongly inhibited the development of microalbuminuria [16].
• A positive correlation was found between the rate of kidney growth and the change in activity of glucose-6-phosphate dehydrogenase and a negative correlation with changes in transketolase activity [17].
• This was achieved by prevention of thiamine depletion and decreased transketolase activity in the liver of diabetic rats [18].
• Plasma total cholesterol, HDL cholesterol and triglycerides were determined at 6-week intervals and hepatic metabolites and transketolase activity after death of the rats at 24 weeks [18].
• In the rat, chronic alcohol feeding for up to 6 months had no effects on tissue thiamin measured by transketolase assay, thiamin pyrophosphate effect, or bioassay with Ochromonas danica [19].

Other interactions of Tkt

• Effect of simultaneous thiamin and riboflavin deficiencies on the determination of transketolase and glutathione reductase [20].
• 1. The activities of 2-oxoglutarate dehydrogenase, transketolase, thiamine pyrophosphokinase and thiamine triphosphatase and the concentrations of thiamine phosphates were almost the same between rat extensor digitorum longus and soleus muscles at 2 weeks of age [21].

Analytical, diagnostic and therapeutic context of Tkt

• Northern blots showed that the transketolase mRNA is approximately 2.2 kb, close to the minimum expected, of which approximately 60% was represented in the largest cDNA clone [6].
• Sequence analysis of the transketolase coding sequences reveals a number of homologies with related enzymes from other species [6].
• With a few exceptions, immunocytochemistry indicated an overall decline of TK immunoreactivity and the decrease was not specific to vulnerable areas [22].
• In contrast to the pronounced, general decline of TK protein, in situ hybridization revealed a regional decrease of 0-25% of TK mRNA in thiamine deficiency [22].
• 1. Multiple forms of the enzyme, with distinct pI values in the range 7-8, have been detected in purified preparations by means of analytical isoelectric focusing and staining for TK [23].

References