Transketolase-related protein

Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Transferase other than ribonuclease

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536 232, 4353201, 4352523, 4352542, C12N 910, C12N 1500, C12N 120, C12N 114, C07H 2104

Patent

active

061330051

DESCRIPTION:

BRIEF SUMMARY
I. FIELD OF THE INVENTION

The present invention relates to a transketolase-related protein, a DNA encoding the same and a process for the preparation thereof. In addition, this invention concerns the use of the DNA and the protein as well as antibodies directed against the protein.


II. BACKGROUND OF THE INVENTION

Transketolase is a thiamine-dependent enzyme which links the pentose phosphate pathway with the glycolysis. The pentose phosphate pathway provides sugar phosphates and NADPH. Transketolase introduces excess sugar phosphates into the glycolysis to as to ensure the provision of NADPH under various metabolic conditions. NADPH is essential for maintaining glutathione in the brain.
Thiamine deficiency is associated with neurologic diseases such as beriberi and Wernicke-Korsakoff syndrome. Beriberi manifests itself in acute heart failure, whereas the Wernicke-Korsakoff syndrome shows as acute encephalopathy followed by chronic damage of the short-term memory.
Investigations refer to the fact that thiamine deficiency is not the cause of the above diseases. Also, no mutated transketolase exists in patients suffering from these diseases, e.g., in patients suffering from the Wernicke-Korsakoff syndrome. Thus, the cause of the above diseases is not known by now.
Therefore, it is the object of the present invention to provide a product by which neurologic diseases associated with thiamine deficiency, particularly beriberi and Wernicke-Korsakoff syndrome, can be investigated as regards their cause and optionally be treated.


III. SUMMARY OF THE INVENTION

The present invention relates to a transketolase-related protein, a DNA encoding the same and a process for the preparation thereof. In addition, the invention concerns the use of the DNA and the protein as well as antibodies directed against the protein.


IV. BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the base sequence (SEQ ID NO:1) and the amino acid sequence (SEQ ID NOS:2), derived therefrom, of a (TVP) according to the invention.
FIG. 2 shows the base sequence (SEQ ID NO:3) and the amino acid sequence (SEQ ID NO:4), derived therefrom, of a brain-specific (TVP) according to the invention (arrows indicate the position of (TVP) of FIG. 1).
FIG. 3 shows the base sequence (SEQ ID NO:5) and the amino acid sequence (SEQ ID NO:6), derived therefrom, of a heart-specific (TVP) according to the invention (arrows indicate the position of (TVP) of FIG. 1).


V. DETAILED DESCRIPTION OF THE INVENTION

It is the object of the present invention to provide a product by which neurologic diseases associated with thiamine deficiency, particularly beriberi and Wernicke-Korsakoff syndrome, can be investigated as regards their cause and optionally be treated. According to the invention, this is achieved by the subject matters defined in the claims.
Thus, the subject matter of the present invention relates to a transketolase-related protein, the protein comprising at least the amino acid sequence of FIG. 1 or an amino acid sequence differing therefrom by one or more amino acids.
The present invention is based on the applicant's finding that in animals, particularly mammals, more particularly human beings, there exists a protein which has homologies with respect to a transketolase, optionally a transketolase activity, but differs from a transketolase on the DNA level by hybridization under normal conditions. Such a protein comprises at least the amino acid sequence of FIG. 1 or an amino acid sequence differing therefrom by one or more amino acids. In addition, the protein is present in various tissues, e.g., brain and heart, in differing form.
The above protein is referred to as "transketolase-related protein" (TVP) in the present invention.
In a preferred embodiment, a (TVP) comprises the amino acid sequence of FIG. 2. Such a (TVP) is found especially in the brains of animals, particularly mammals, more particularly human beings.
In a further preferred embodiment, a (TVP) includes the amino acid sequence of FIG. 3. Such a (TVP) is found especially in the hearts of anim

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