In thiamine deficiency, activation of erythrocyte transketolase by thiamine in vivo exceeds activation by cofactor in vitro

Price, John; Clague, Alan; Kerr, Ray; Nixon, P.G.F.

doi:10.1016/0009-8981(91)90253-9

Cited by 4 publications

(6 citation statements)

References 10 publications

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“…Indeed the rapid symptomatic response of thiamin-de®cient patients to therapeutic thiamin is paralled by the apparent conversion of erythrocyte apoTK to holoTK in vivo within a period as brief as 30 min [123]. Moreover, the total erythrocyte TK activity is restored to the thiamin-replete levels, consistent with the retention of total TK protein throughout the period of thiamin de®ciency.…”

Section: Potential Associations Of Tk Activity With Disorders Consequmentioning

confidence: 81%

“…Erythrocyte TK activity is measured to assess human thiamin de®ciency and assays of hemolysate TK activity in the absence and presence of cofactor added in vitro allow the inference that some apoTK accumulates as holoTK decreases in human thiamin de®ciency [76,114,123]. Indeed the rapid symptomatic response of thiamin-de®cient patients to therapeutic thiamin is paralled by the apparent conversion of erythrocyte apoTK to holoTK in vivo within a period as brief as 30 min [123].…”

Section: Potential Associations Of Tk Activity With Disorders Consequmentioning

confidence: 99%

“…Moreover, the total erythrocyte TK activity is restored to the thiamin-replete levels, consistent with the retention of total TK protein throughout the period of thiamin de®ciency. However, in hemolysates from thiaminde®cient patients, not all the apoTK can be reactivated in vitro, for reasons that are as yet unclear [41,123]. Since mature erythrocytes do not synthesise protein, the half-life of erythrocyte TK protein must be similar to or greater than the half-life of the erythrocyte, i.e.…”

Section: Potential Associations Of Tk Activity With Disorders Consequmentioning

confidence: 99%

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Properties and functions of the thiamin diphosphate dependent enzyme transketolase

Schenk

Duggleby

Nixon

1998

The International Journal of Biochemistry & Cell Biology

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223

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: Potential Associations Of Tk Activity With Disorders Consequmentioning

confidence: 81%

Section: Potential Associations Of Tk Activity With Disorders Consequmentioning

confidence: 99%

Section: Potential Associations Of Tk Activity With Disorders Consequmentioning

confidence: 99%

See 1 more Smart Citation

Properties and functions of the thiamin diphosphate dependent enzyme transketolase

Schenk

Duggleby

Nixon

1998

The International Journal of Biochemistry & Cell Biology

Self Cite

223

164

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“…Price et al . observed a lower activation after in vitro stimulation of ETK compared with in vivo activity following thiamine supplementation that may be related to irreversible inactivation of the enzyme in vitro 40 . Thus, observations in vitro may not represent the in vivo situation.…”

Section: Limitations and Other Factorsmentioning

confidence: 93%

“…Price et al observed a lower activation after in vitro stimulation of ETK compared with in vivo activity following thiamine supplementation that may be related to irreversible inactivation of the enzyme in vitro. 40 Thus, observations in vitro may not represent the in vivo situation. Clinical conditions, for example, certain anemias or diseases that affect erythrocyte cell survival time and the age distribution, may also affect the interpretation of ETKAC.…”

Section: Limitations and Other Factorsmentioning

confidence: 99%

Erythrocyte transketolase activity coefficient (ETKAC) assay protocol for the assessment of thiamine status

Jones

Parkington

Cox

et al. 2020

Annals of the New York Academy of Sciences

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Vitamin B1 (thiamine) is an essential nutrient that acts as a cofactor for a number of metabolic processes, particularly in energy metabolism. Symptoms of classic thiamine deficiency are recognized as beriberi, although clinical symptoms are nonspecific and recognition of subclinical deficiency is difficult. Therefore, reliable biomarkers of thiamine status are required. Thiamine diphosphate is a cofactor for transketolase, including erythrocyte transketolase (ETK). The ETK activity assay as an indirect, functional marker of thiamine status has been used for over 50 years. The ETK activity assay provides a sensitive and specific biomarker of thiamine status; however, there is a lack of consensus over the cutoffs for deficiency, partly due to a lack of assay harmonization. Here, we provide a step‐by‐step protocol for the measurement of ETK activity and the calculation of the ETK activity coefficient, including detailed explanations of equipment and chemicals required and guidance for quality control procedures. Harmonization of the protocol will provide the basis for the development of internationally recognized cutoffs for thiamine insufficiency. The establishment of quality control materials and a quality assurance scheme are recommended to provide reliability. This will ensure that the ETK activity assay remains an important method for the assessment of thiamine status.

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Thiamine Pyrophosphate Effect and Normalized Erythrocyte Transketolase Activity Ratio in Wernicke-Korsakoff Patients and Acute Alcoholics Undergoing Detoxification

Rooprai

Pratt²,

Shaw³

et al. 1996

Alcohol and Alcoholism

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Thiamine deficiency may be assessed clinically by an abnormally low specific erythrocyte transketolase activity and/or by abnormally large activation by thiamine diphosphate in vitro (or 'TPP effect'). In the present investigation, we report erythrocyte transketolase activation by TPP in acute alcoholics and Wernicke-Korsakoff patients undergoing detoxification. A new age-dependent parameter was used to improve the reliability of transketolase activity as an indicator of marginal thiamine deficiency. Thus normalized transketolase activity ratio (NTKZ), primary activation ratio (PAR) and further activation ratio (FAR) were measured in 29 acute alcoholics and 12 Wernicke-Korsakoff patients upon admission, and also on 47 control subjects. It was possible to follow up 14 of the 29 acute alcoholics after 7 days of treatment. Twenty-one per cent of the acute alcoholics and 33% of the Wernicke-Korsakoff patients, on admission to the detoxification Unit, had NTKZ values beyond the defined critical conditions for thiamine deficiency, whereas 7% of the former and 25% of the latter had PAR values beyond these critical conditions. Furthermore, all three parameters were significantly different in the Wernicke-Korsakoff patients compared to the other groups. The pattern of improvement of the different parameters on follow-up varied considerably and is difficult to explain, as only the NTKZ was statistically significant. Hence, only eight out of 14 acute alcoholics showed improvement in NTKZ, seven showed improvement of PAR and six showed improvement of FAR after treatment. Five patients showed improvement of both NTKZ and PAR and none of the patients showed improvement of all three parameters. We conclude that our findings confirm previous reports and that this modified transketolase activation test improves its reliability as an indicator of marginal thiamine deficiency.

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In thiamine deficiency, activation of erythrocyte transketolase by thiamine in vivo exceeds activation by cofactor in vitro

Cited by 4 publications

References 10 publications

Properties and functions of the thiamin diphosphate dependent enzyme transketolase

Properties and functions of the thiamin diphosphate dependent enzyme transketolase

Erythrocyte transketolase activity coefficient (ETKAC) assay protocol for the assessment of thiamine status

Thiamine Pyrophosphate Effect and Normalized Erythrocyte Transketolase Activity Ratio in Wernicke-Korsakoff Patients and Acute Alcoholics Undergoing Detoxification

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