Cloning of human transketolase cDNAs and comparison of the nucleotide sequence of the coding region in Wernicke-Korsakoff and non-Wernicke-Korsakoff individuals
Variants of the enzyme transketolase which possess reduced affinity for its cofactor thiamine pyrophosphate (high apparent Km) have been described in chronic alcoholic patients with Wernicke-Korsakoff syndrome. Since the syndrome has been shown to be directly related to thiamine deficiency, it has b...
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Published in | The Journal of biological chemistry Vol. 268; no. 2; pp. 1397 - 1404 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Bethesda, MD
American Society for Biochemistry and Molecular Biology
15.01.1993
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Subjects | |
Online Access | Get full text |
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Summary: | Variants of the enzyme transketolase which possess reduced affinity for its cofactor thiamine pyrophosphate (high apparent
Km) have been described in chronic alcoholic patients with Wernicke-Korsakoff syndrome. Since the syndrome has been shown
to be directly related to thiamine deficiency, it has been hypothesized that such transketolase variants may represent a genetic
predisposition to the development of this syndrome. To test this hypothesis, human transketolase cDNA clones were isolated,
and their nucleotide and predicted amino acid sequence were determined. Transketolase was found to be a single copy gene which
produces a single mRNA of approximately 2100 nucleotides. Additionally, the nucleotide sequence of the transketolase coding
region in fibroblasts derived from two Wernicke-Korsakoff (WK) patients was compared to that of two nonalcoholic controls.
Although nucleotide and predicted amino acid differences were detected between fibroblast cultures and the original cDNAs
and among the cultures themselves, no specific nucleotide variations, which would encode a variant amino acid sequence, were
associated exclusively with the coding region from WK patients. Thus, allelic variants of the transketolase gene cannot account
for the biochemically distinct forms of the enzyme found in these patients nor be considered as a mechanism for genetic predisposition
to the development of Wernicke-Korsakoff syndrome. Instead, the underlying mechanism must be extragenic and may be a result
of differences in post-translational processing/modification of the transketolase polypeptide. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/S0021-9258(18)54089-8 |