Variants of transketolase from human erythrocytes

Kaczmarek, M; Nixon, P.G.F.

doi:10.1016/0009-8981(83)90309-1

Cited by 43 publications

(17 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The last two tests are functional rather than a direct measurement of thiamine status and therefore may be influenced by factors other than thiamine deficiency. These include loss of reactivatable apoenzyme during chronic deficiency in vivo , altered binding of apoenzyme and coenzyme because of the presence of isoenzymes of TK and reduced synthesis of apoenzyme in patients with diabetes and liver disease , among other technical factors . If no appropriate controls are available, these factors may have contributed to the lack of agreement over the upper limit of the reference range for the activation assay, with values ranging from 15.5% to 40% .…”

Section: Methodsmentioning

confidence: 99%

Thiamine Deficiency‐Mediated Brain Mitochondrial Pathology in Alaskan Huskies with Mutation in SLC19A3.1

et al. 2014

View full text Add to dashboard Cite

Alaskan Husky encephalopathy (AHE1) is a fatal brain disease associated with a mutation in SLC19A3.1 (c.624insTTGC, c.625C>A). This gene encodes for a thiamine transporter 2 with a predominantely central nervous system (CNS) distribution. Considering that brain is particularly vulnerable to thiamine deficiency due to its reliance on TPP-dependent metabolic pathways involved in energy metabolism and neurotransmitter synthesis, we characterized the impact of this mutation on thiamine status, brain bioenergetics, and the contribution of oxidative stress to this phenotype. In silico modeling of the mutated transporter indicated a significant loss of alpha-helices resulting in a more open protein structure suggesting an impaired thiamine transport ability. The cerebral cortex and thalamus of affected dogs were severely deficient in TPP-dependent enzymes accompanied by decreases in mitochondrial mass and OXPHOS capacity, and increases in oxidative stress. These results along with the behavioral and pathological findings indicate that the phenotype associated with AHE is consistent with a brain-specific thiamine deficiency, leading to brain mitochondrial dysfunction and increased oxidative stress. While some of the biochemical deficits, neurobehavior and affected brain areas in AHE were shared by Wernicke's and Korsakoff's syndromes, several differences were noted likely arising from a tissue-specific vs. that from a whole-body thiamine deficiency.

show abstract

Section: Methodsmentioning

confidence: 99%

Thiamine Deficiency‐Mediated Brain Mitochondrial Pathology in Alaskan Huskies with Mutation in SLC19A3.1

et al. 2014

View full text Add to dashboard Cite

show abstract

“…When a pure erythrocyte TK preparation from a single individual was analysed by application of this method, the enzyme resolved into three to eight distinct bands [73]. Focussed bands containing TK were detected by a speci®c activity stain [182].…”

Section: Variant Forms Of Tkmentioning

confidence: 99%

Properties and functions of the thiamin diphosphate dependent enzyme transketolase

Schenk

Duggleby

Nixon

1998

The International Journal of Biochemistry & Cell Biology

Self Cite

220

164

View full text Add to dashboard Cite

This review highlights recent research on the properties and functions of the enzyme transketolase, which requires thiamin diphosphate and a divalent metal ion for its activity. The transketolase-catalysed reaction is part of the pentose phosphate pathway, where transketolase appears to control the non-oxidative branch of this pathway, although the overall¯ux of labelled substrates remains controversial. Yeast transketolase is one of several thiamin diphosphate dependent enzymes whose three-dimensional structures have been determined. Together with mutational analysis these structural data have led to detailed understanding of thiamin diphosphate catalysed reactions. In the homodimer transketolase the two catalytic sites, where dihydroxyethyl groups are transferred from ketose donors to aldose acceptors, are formed at the interface between the two subunits, where the thiazole and pyrimidine rings of thiamin diphosphate are bound. Transketolase is ubiquitous and more than 30 full-length sequences are known. The encoded protein sequences contain two motifs of high homology; one common to all thiamin diphosphate-dependent enzymes and the other a unique transketolase motif. All characterised transketolases have similar kinetic and physical properties, but the mammalian enzymes are more selective in substrate utilisation than the nonmammalian representatives. Since products of the transketolase-catalysed reaction serve as precursors for a number of synthetic compounds this enzyme has been exploited for industrial applications. Putative mutant forms of transketolase, once believed to predispose to disease, have not stood up to scrutiny. However, a modi®cation of transketolase is a marker for Alzheimer's disease, and transketolase activity in erythrocytes is a measure of thiamin nutrition. The cornea contains a particularly high transketolase concentration, consistent with the proposal that pentose phosphate pathway activity has a role in the removal of light-generated radicals. #

show abstract

“…Both describe the measurement of TDP as a more sensitive and specific index of thiamin status. The assessment of TDP is more specific since the ETKA assay may be influenced by factors other than thiamin deficiency [12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Determination of thiamin diphosphate in whole blood samples by high-performance liquid chromatography—A method suitable for pediatric diagnostics

Körner¹,

Vierzig²,

Roth³

et al. 2009

Journal of Chromatography B

View full text Add to dashboard Cite

Variants of transketolase from human erythrocytes

Cited by 43 publications

References 7 publications

Thiamine Deficiency‐Mediated Brain Mitochondrial Pathology in Alaskan Huskies with Mutation in SLC19A3.1

Thiamine Deficiency‐Mediated Brain Mitochondrial Pathology in Alaskan Huskies with Mutation in SLC19A3.1

Properties and functions of the thiamin diphosphate dependent enzyme transketolase

Determination of thiamin diphosphate in whole blood samples by high-performance liquid chromatography—A method suitable for pediatric diagnostics

Contact Info

Product

Resources

About