Transketolase abnormality in cultured fibroblasts from familial chronic alcoholic men and their male offspring.

Mukherjee, Anil B.; Svoronos, Soraya; Ghazanfari, A; Martin, Peter; Fisher, Anne E.; Roecklein, Bryan A.; Rodbard, David; Staton, Richard C.; Béhar, David; Berg, Chantal van den

doi:10.1172/jci112916

Cited by 78 publications

(25 citation statements)

References 19 publications

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“…The authors suggested that the patients were genetically predisposed to this disorder. Their results were later supported by Mukherjee et al [107] although the observed di erence between the apparent cofactor binding constants for patients and controls was much smaller. In this laboratory TK isolated from erythrocytes of WK syndrome patients and controls did not display any variation in ThDP a nity [113].…”

Section: Variant Forms Of Tkmentioning

confidence: 69%

Properties and functions of the thiamin diphosphate dependent enzyme transketolase

Schenk

Duggleby

Nixon

1998

The International Journal of Biochemistry & Cell Biology

221

164

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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. #

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Section: Variant Forms Of Tkmentioning

confidence: 69%

Properties and functions of the thiamin diphosphate dependent enzyme transketolase

Schenk

Duggleby

Nixon

1998

The International Journal of Biochemistry & Cell Biology

221

164

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“…TKT catalyzes several reactions within the nonoxidative branch of the PP pathway, and together with transaldolase serves as a reversible link between the PP and glycolytic pathways, allowing the cell to adapt to a variety of metabolic needs under changing environmental conditions. TKT is often used to assess thiamine status in man (18), and alterations in TKT chemicophysical or kinetic properties have been implicated in a variety of pathological conditions including Wernicke-Korsakoff's Syndrome (19,20), Alzheimer's disease (21,22), fibromyalgia (23), severe malnutrition (24,25), and alcoholism (26).…”

mentioning

confidence: 99%

Transketolase Is a Major Protein in the Mouse Cornea

Salamon

et al. 1996

Journal of Biological Chemistry

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Earlier experiments in this laboratory identified a highly expressed 65-68-kDa protein in both mouse and human corneas (Cuthbertson, R. A., Tomarev, S. I., and Piatigorsky J. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 4004 -4008). Here, we demonstrate that this protein is transketolase (TKT; EC 2.2.1.1), an enzyme in the nonoxidative branch of the pentose-phosphate pathway, based on peptide and cDNA isolation and sequence analysis of mouse cornea protein and RNA samples, respectively. While expressed at low levels in a number of tissues, the 2.1-kilobase TKT mRNA was expressed at a 50-fold higher level in the adult mouse cornea. The area of most abundant expression was localized to the cornea epithelial cell layer by in situ hybridization. Western blot analysis confirmed TKT protein abundance in the cornea and indicated that TKT may comprise as much as 10% of the total soluble protein of the adult mouse cornea. Soluble cornea extracts exhibited a correspondingly high level of TKT enzymatic activity. TKT expression increased progressively through cornea maturation, as shown by Northern blot, in situ hybridization, Western blot, and enzymatic analyses. TKT mRNA and protein were expressed at low levels in the cornea prior to eye opening, while markedly increased levels were observed after eye opening. Taken together, these observations suggest that TKT may be a cornea enzymecrystallin, and suggest that the crystallin paradigm and concept of gene sharing, once thought to be restricted to the lens, apply to other transparent ocular tissues.

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“…In the other patients WE appears to be an uncommon complication of common medical conditions (such as hyperemesis of pregnancy, hemodialysis and banded gastroplasy), a fact which also suggests that the development of the disorder depends on a predisposition which may be genetic. It was suggested that altered transketolase activity may predispose patients to alcohol-associated WE [13, 14]but sequencing of the enzyme’s coding region failed to demonstrate a specific variation which may account for an altered enzyme activity [15]. Future advances in the biochemistry and genetics of thiamine-dependent enzymes may define the precise abnormality and set guidelines for appropriate replacement therapy in such patients.…”

Section: Discussionmentioning

confidence: 99%

Thiamine-Responsive Acute Neurological Disorders in Nonalcoholic Patients

Merkin-Zaborsky

Ifergane²,

Frisher³

et al. 2001

Eur Neurol

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Wernicke’s encephalopathy (WE) is most commonly associated with alcoholism, although other causes have also been implicated. In the years 1994–1997, 9 patients with no history of alcohol abuse presented with acute signs of ophthalmoplegia or nystagmus and ataxia which resolved within 48 h after intravenous thiamine. There were 7 women and 2 men aged 17–57 (7 below the age of 30). Precipitating events included vomiting 2, drastic weight-reducing diet 2, renal colic in a postpartum woman 1, colonic surgery 2 and chronic hemodialysis 1. In 2 patients there was no obvious precipitating event but their history was suggestive of a genetic predisposition. Mental changes were slight or absent in all patients and all of them made good functional recovery. These cases suggest that the diagnosis of WE should be considered more often in nonalcoholics in various clinical settings.

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Transketolase abnormality in cultured fibroblasts from familial chronic alcoholic men and their male offspring.

Cited by 78 publications

References 19 publications

Properties and functions of the thiamin diphosphate dependent enzyme transketolase

Properties and functions of the thiamin diphosphate dependent enzyme transketolase

Transketolase Is a Major Protein in the Mouse Cornea

Thiamine-Responsive Acute Neurological Disorders in Nonalcoholic Patients

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