Abstract
To study the effect of sodium benzoate on carnitine metabolism, the acylcarnitine profile in the urine of five normal volunteers and two patients with urea cycle disorders was examined with fast atom bombardment-mass spectrometry. The volunteer subjects were given 5 g of sodium benzoate orally and the two patients with urea cycle disorders (carbamyl phosphate synthetase deficiency type I and ornithine transcarbamylase deficiency) were already undergoing treatment with sodium benzoate and L-carnitine. The amount of benzoylcarnitine excretion depended on the dose of both sodium benzoate and L-carnitine in a reciprocal relation. Increased excretions of acetylcarnitine and propionylcarnitine were also noted after sodium benzoate administration. The alteration of the urinary aclycarnitine profile was consistent with the change of mitochondrial CoA profile predicted by in vitro studies of an animal model. It is suggested that urinary acylcarnitine analysis is important to assess the effect of benzoate administration on mitochondrial function in vivo. Supplementation with carnitine may be necessary to minimise the adverse effects of sodium benzoate treatment in hyperammonaemia.
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- Brusilow S. W., Valle D. L., Batshaw M. New pathways of nitrogen excretion in inborn errors of urea synthesis. Lancet. 1979 Sep 1;2(8140):452–454. doi: 10.1016/s0140-6736(79)91503-4. [DOI] [PubMed] [Google Scholar]
- Brusilow S., Tinker J., Batshaw M. L. Amino acid acylation: a mechanism of nitrogen excretion in inborn errors of urea synthesis. Science. 1980 Feb 8;207(4431):659–661. doi: 10.1126/science.6243418. [DOI] [PubMed] [Google Scholar]
- Cohen N. S., Cheung C. W., Raijman L. The effects of ornithine on mitochondrial carbamyl phosphate synthesis. J Biol Chem. 1980 Nov 10;255(21):10248–10255. [PubMed] [Google Scholar]
- Kidouchi K., Sugiyama N., Morishita H., Kobayashi M., Wada Y., Nohara D. Identification of glutarylcarnitine in glutaric aciduria type 1 by carboxylic acid analyzer with an ODS reverse-phase column. Clin Chim Acta. 1987 May 15;164(3):261–266. doi: 10.1016/0009-8981(87)90300-7. [DOI] [PubMed] [Google Scholar]
- Matsuda I., Ohtani Y., Ohyanagi K., Yamamoto S. Hyperammonemia related to carnitine metabolism with particular emphasis on ornithine transcarbamylase deficiency. Enzyme. 1987;38(1-4):251–255. doi: 10.1159/000469212. [DOI] [PubMed] [Google Scholar]
- McCune S. A., Durant P. J., Flanders L. E., Harris R. A. Inhibition of hepatic gluconeogenesis and lipogenesis by benzoic acid, p-tert.-butylbenzoic acid, and a structurally related hypolipidemic agent SC-33459. Arch Biochem Biophys. 1982 Mar;214(1):124–133. doi: 10.1016/0003-9861(82)90014-5. [DOI] [PubMed] [Google Scholar]
- Montgomery J. A., Mamer O. A. Measurement of urinary free and acylcarnitines: quantitative acylcarnitine profiling in normal humans and in several patients with metabolic errors. Anal Biochem. 1989 Jan;176(1):85–95. doi: 10.1016/0003-2697(89)90277-7. [DOI] [PubMed] [Google Scholar]
- O'Connor J. E., Costell M., Grisolía S. The potentiation of ammonia toxicity by sodium benzoate is prevented by L-carnitine. Biochem Biophys Res Commun. 1987 Jun 15;145(2):817–824. doi: 10.1016/0006-291x(87)91038-2. [DOI] [PubMed] [Google Scholar]
- Sakuma T., Asai K., Ichiki T., Sugiyama N., Kidouchi K., Wada Y. Identification of benzoylcarnitine in the urine of a patient of hyperammonemia. Tohoku J Exp Med. 1989 Oct;159(2):147–151. doi: 10.1620/tjem.159.147. [DOI] [PubMed] [Google Scholar]
- Swartzentruber M. S., Harris R. A. Inhibition of metabolic processes by coenzyme-A-sequestering aromatic acids. Prevention by para-chloro- and para-nitrobenzoic acids. Biochem Pharmacol. 1987 Oct 1;36(19):3147–3153. doi: 10.1016/0006-2952(87)90625-3. [DOI] [PubMed] [Google Scholar]
- Tomokuni K., Ogata M. Direct colorimetric determination of hippuric acid in urine. Clin Chem. 1972 Apr;18(4):349–351. [PubMed] [Google Scholar]