Disease relevance of TKL1

• From a genetic point of view, it is well known that several micro-organisms, including Escherichia coli and S. cerevisiae, contain multiple genes encoding isoenzymes of transketolase and transaldolase [1].
• Baker's yeast transketolase inactivated by tetranitromethane was digested with Staphylococcus aureus V8 protease [2].
• We report further evidence that the recP protein from Streptococcus pneumoniae might be a transketolase and we list a number of invariant residues which might be involved in substrate binding [3].
• Enzymic formation of glycolate in Chromatium. Role of superoxide radical in a transketolase-type mechanism [4].
• The role of cysteine 160 in thiamine diphosphate binding of the Calvin-Benson-Bassham cycle transketolase of Rhodobacter sphaeroides [5].

Psychiatry related information on TKL1

• However, a modification of transketolase is a marker for Alzheimer's disease, and transketolase activity in erythrocytes is a measure of thiamin nutrition [6].

High impact information on TKL1

• Three-dimensional structure of transketolase, a thiamine diphosphate dependent enzyme, at 2.5 A resolution [7].
• Snapshot of a key intermediate in enzymatic thiamin catalysis: crystal structure of the alpha-carbanion of (alpha,beta-dihydroxyethyl)-thiamin diphosphate in the active site of transketolase from Saccharomyces cerevisiae [8].
• Kinetic and spectroscopic data indicated that addition of the donor substrate hydroxypyruvate to the thiamin diphosphate (ThDP)-dependent enzyme transketolase (TK) led to the accumulation of the alpha-carbanion/enamine of (alpha,beta-dihydroxyethyl) ThDP, the key reaction intermediate in enzymatic thiamin catalysis [8].
• The HU sensitivity of sod1Delta and lys7Delta strains is suppressed by overexpression of TKL1, a transketolase that generates NADPH, which balances redox in the cell and is required for ribonucleotide reductase activity [9].
• This also applies to transketolase, transaldolase and fructose-1,6-bisphosphatase [10].

Chemical compound and disease context of TKL1

• Histidine 407, a phantom residue in the E1 subunit of the Escherichia coli pyruvate dehydrogenase complex, activates reductive acetylation of lipoamide on the E2 subunit. An explanation for conservation of active sites between the E1 subunit and transketolase [11].

Biological context of TKL1

• This gene, LTP1, together with a neighboring gene, TKL1, is shown to be located on the right arm of chromosome XVI [12].
• Here we report that these two sod1Delta phenotypes were specifically suppressed by elevated expression of the TKL1 gene, encoding transketolase of the pentose phosphate pathway [13].
• In addition, transformation of the tkl1 tkl2 double mutant with the TKL2 plasmid can compensate the growth defect on a medium without aromatic amino acids [14].
• Yeast TKL1 gene encodes a transketolase that is required for efficient glycolysis and biosynthesis of aromatic amino acids [15].
• The gene specifying plastid transketolase (TK) of maize (Zea mays) was cloned from a cDNA library by southern blotting using a heterologous probe from sorghum (Sorghum bicolor) [16].

Anatomical context of TKL1

• In addition, transketolase, transaldolase, and glucose-6-phosphatase, a known cisternal enzyme, are inactivated by chymotrypsin and subtilisin only in disrupted hepatic microsomes under conditions in which NADPH-cytochrome c reductase, an enzyme on the external surface, is inactivated equally in intact and disrupted microsomes [17].
• By coupling baker's yeast transketolase with illuminated chromatophore preparations, it was demonstrated that [U-14C]-fructose 6-phosphate (6-P) is oxidatively split to produce glycolate, and that the reaction was markedly inhibited by superoxide dismutase and less strongly by catalase [4].
• The determination of thiamin pyrophosphate in blood and other tissues, and its correlation with erythrocyte transketolase activity [18].
• Immunogold electron microscopy on spinach leaf thin sections revealed that about 90% of the total epimerase and transketolase, and 96% of the total chloroplast H+-ATP synthase portion CF1 are associated with thylakoid membranes in situ [19].

Associations of TKL1 with chemical compounds

• We determined that a functional ZWF1 gene product was required for TKL1 to suppress sod1Delta, leading us to propose that increased flux through the oxidative reactions of the pentose phosphate pathway can rescue sod1 methionine auxotrophy [13].
• Yeast mutants with a deletion of the transketolase gene, TKL1, can grow without aromatic amino acid supplement indicating an additional source of erythrose 4-phosphate in the cells [14].
• Fermentation of the recombinant S. cerevisiae strains containing XYL1, XYL2, TKL1, and TAL1 were studied with mixtures of glucose and xylose [20].
• Interestingly, all mutants tested (glucose 6-phosphate dehydrogenase, gluconate 6-phosphate dehydrogenase, ribulose 5-phosphate epimerase, transketolase, transaldolase) are sensitive to hydrogen peroxide [21].
• Activities of the key enzymes in the pentose phosphate pathway (transketolase, transaldolase) increased 2-fold while the concentrations of their substrates (pentose 5-phosphates, sedoheptulose 7-phosphate) decreased correspondingly [22].

Other interactions of TKL1

• The deduced protein sequence of TKL2 demonstrates 71% identity with TKL1 [Sundström, M., Lindqvist, Y., Schneider, G., Hellman, U. & Ronne, H. (1993) J. Biol. Chem., in the press] [14].
• Pentose-phosphate pathway in Saccharomyces cerevisiae: analysis of deletion mutants for transketolase, transaldolase, and glucose 6-phosphate dehydrogenase [23].
• A recombinant fusion protein comprising thioredoxin of Escherichia coli and mature TK of maize was expressed at a high level in E. coli and cleaved with thrombin, affording plastid TK [16].

Analytical, diagnostic and therapeutic context of TKL1

• Transketolase protein could be detected as a single protein band of the expected size by Western-blot analysis in wild-type strains but not in the deletion mutant [23].
• Examination of substrate binding in thiamin diphosphate-dependent transketolase by protein crystallography and site-directed mutagenesis [24].
• The cleavage of the donor substrate d-xylulose 5-phosphate by wild-type and H263A mutant yeast transketolase was studied using enzyme kinetics and circular dichroism spectroscopy [25].
• Chemically synthesized dl-(alpha,beta-dihydroxyethyl)thiamin diphosphate is bound to wild-type transketolase with an apparent K(D) of 4.3 +/- 0.8 microm (racemate) calculated from titration experiments using circular dichroism spectroscopy [25].
• The affinity chromatography of transketolase [26].

References