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Journal of Lipid Research, Vol. 41, 1543-1551, October 2000
Copyright © 2000 by Lipid Research, Inc.

Original Article

Urinary {alpha}-tocopherol metabolites in {alpha}-tocopherol transfer protein-deficient patients

Markus Schuelkea, Angelika Elsnerb, Barbara Finckhd, Alfried Kohlschütterd, Christoph Hübnera, and Regina Brigelius-Flohéb,c
a Department of Neuropediatrics, Charité University Hospital, Humboldt University Berlin, D-13353 Berlin, Germany
b German Institute of Human Nutrition, D-14558 Potsdam-Rehbrücke, Germany
c Institute for Nutritional Science, University of Potsdam, D-14458 Potsdam-Rehbrücke, Germany
d Children's Hospital, University of Hamburg, D-20246 Hamburg, Germany

Correspondence to: Regina Brigelius-Flohé

Patients with {alpha}-tocopherol transfer protein ({alpha}-TTP) defects experience neurological symptoms characteristic of vitamin E deficiency and depend on continuous high {alpha}-tocopherol supplements. We investigated the excretion of 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman ({alpha}-CEHC), a urinary metabolite of {alpha}-tocopherol, as a putative marker for the {alpha}-tocopherol status of {alpha}-TTP-deficient patients and control subjects. In three patients vitamin E supplementation was stopped for short periods of time, during which plasma {alpha}-tocopherol concentrations and urinary {alpha}-CEHC excretion were measured. In the patients, plasma {alpha}-tocopherol decreased below normal (<5 µmol/l) but {alpha}-CEHC excretion remained above the range of unsupplemented control subjects (0.118;–0.306 mg/day, n = 6). In healthy subjects, however, {alpha}-CEHC excretion was increased only after surpassing a plasma {alpha}-tocopherol threshold of 30;–40 µmol/l. Such a threshold did not exist in patients. The general mechanism of {alpha}-tocopherol degradation did not appear to differ between patients and control subjects.

The presumed mechanism of {omega}- and subsequent ß-oxidation was supported by the detection of {alpha}-CPHC, an {alpha}-CEHC homolog with a side chain longer by 3 carbon atoms, both in supplemented patients and in control subjects. — Schuelke, M., A. Elsner, B. Finckh, A. Kohlschütter, C. Hübner, and R. Brigelius-Flohé. Urinary {alpha}-tocopherol metabolites in {alpha}-tocopherol transfer protein-deficient patients. J. Lipid Res. 2000. 41: 1543;–1551.

Supplementary key words: {alpha}-tocopherol, {alpha}-tocopherol metabolites, {alpha}-CEHC, {alpha}-tocopherol transfer protein, AVED patients


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