Urinary alpha-tocopherol metabolites in alpha-tocopherol transfer protein-deficient patients.
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 micromol/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 micromol/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 beta-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
M
Department of Neuropediatrics, Charité University Hospital, Humboldt University Berlin, D-13353 Berlin, Germany.
Elsner
A
A
Finckh
B
B
Kohlschütter
A
A
Hübner
C
C
Brigelius-Flohé
R
R
D000293:Adolescent; D000328:Adult; D001259:Ataxia / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D002839:Chromans / Q000737:chemistry / Q000652:urine; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D010421:Pentanoic Acids / Q000737:chemistry / Q000652:urine; D011422:Propionates / Q000652:urine; D014810:Vitamin E / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D014811:Vitamin E Deficiency / Q000235:genetics / Q000378:metabolism
C417622:2,5,7,8-tetramethyl-2-(4'-carboxypentyl)-6-hydroxychroman; D002352:Carrier Proteins; D002839:Chromans; D010421:Pentanoic Acids; D011422:Propionates; C017763:alpha-tocopherol transfer protein; D014810:Vitamin E; C084852:2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman