Abstract
An automated enzymatic method was developed for the measurement of D-arabinitol in human serum. The assay is based on a novel, highly specific D-arabinitol dehydrogenase from Candida tropicalis. This enzyme catalyzes the oxidation of D-arabinitol to D-ribulose and the concomitant reduction of NAD+ to NADH. The NADH produced is used in a second reaction to reduce p-iodonitrotetrazolium violet (INT) to INT-formazan, which is measured spectrophotometrically. The entire reaction sequence can be performed automatically on a COBAS MIRA-S clinical chemistry analyzer (Roche Diagnostic Systems, Inc., Montclair, N.J.). Replicate analyses of human sera supplemented with D-arabinitol over a concentration range of 0 to 40 microM demonstrated that the pentitol could be measured with an accuracy of +/- 7% and a precision (standard deviation) of +/- 0.4 microM. Serum D-arabinitol measurements correlated with those determined by gas chromatography (r = 0.94). The enzymatic method is unaffected by L-arabinitol, D-mannitol, or other polyols commonly found in human serum. Any of 17 therapeutic drugs potentially present in serum did not significantly influence assay performance. Data illustrating the application of the assay in patients for possible diagnosis of invasive candidiasis and the monitoring of therapeutic intervention are presented. The automated assay described here was developed to facilitate the investigation of D-arabinitol as a serum marker for invasive Candida infections.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bernard E. M., Christiansen K. J., Tsang S. F., Kiehn T. E., Armstrong D. Rate of arabinitol production by pathogenic yeast species. J Clin Microbiol. 1981 Aug;14(2):189–194. doi: 10.1128/jcm.14.2.189-194.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bernard E. M., Wong B., Armstrong D. Stereoisomeric configuration of arabinitol in serum, urine, and tissues in invasive candidiasis. J Infect Dis. 1985 Apr;151(4):711–715. doi: 10.1093/infdis/151.4.711. [DOI] [PubMed] [Google Scholar]
- Bougnoux M. E., Hill C., Moissenet D., Feuilhade de Chauvin M., Bonnay M., Vicens-Sprauel I., Pietri F., McNeil M., Kaufman L., Dupouy-Camet J. Comparison of antibody, antigen, and metabolite assays for hospitalized patients with disseminated or peripheral candidiasis. J Clin Microbiol. 1990 May;28(5):905–909. doi: 10.1128/jcm.28.5.905-909.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Horn R., Wong B., Kiehn T. E., Armstrong D. Fungemia in a cancer hospital: changing frequency, earlier onset, and results of therapy. Rev Infect Dis. 1985 Sep-Oct;7(5):646–655. doi: 10.1093/clinids/7.5.646. [DOI] [PubMed] [Google Scholar]
- Jones J. M. Laboratory diagnosis of invasive candidiasis. Clin Microbiol Rev. 1990 Jan;3(1):32–45. doi: 10.1128/cmr.3.1.32. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kiehn T. E., Bernard E. M., Gold J. W., Armstrong D. Candidiasis: detection by gas-liquid chromatography of D-arabinitol, a fungal metabolite, in human serum. Science. 1979 Nov 2;206(4418):577–580. doi: 10.1126/science.493963. [DOI] [PubMed] [Google Scholar]
- Lecciones J. A., Lee J. W., Navarro E. E., Witebsky F. G., Marshall D., Steinberg S. M., Pizzo P. A., Walsh T. J. Vascular catheter-associated fungemia in patients with cancer: analysis of 155 episodes. Clin Infect Dis. 1992 Apr;14(4):875–883. doi: 10.1093/clinids/14.4.875. [DOI] [PubMed] [Google Scholar]
- Neuberger M. S., Patterson R. A., Hartley B. S. Purification and properties of Klebsiella aerogenes D-arabitol dehydrogenase. Biochem J. 1979 Oct 1;183(1):31–42. doi: 10.1042/bj1830031. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Quong M. W., Miyada C. G., Switchenko A. C., Goodman T. C. Identification, purification, and characterization of a D-arabinitol-specific dehydrogenase from Candida tropicalis. Biochem Biophys Res Commun. 1993 Nov 15;196(3):1323–1329. doi: 10.1006/bbrc.1993.2397. [DOI] [PubMed] [Google Scholar]
- Roboz J., Kappatos D. C., Greaves J., Holland J. F. Determination of polyols in serum by selected ion monitoring. Clin Chem. 1984 Oct;30(10):1611–1615. [PubMed] [Google Scholar]
- Roboz J., Nieves E., Holland J. F. Separation and quantification by gas chromatography-mass spectrometry of arabinitol enantiomers to aid the differential diagnosis of disseminated candidiasis. J Chromatogr. 1990 Feb 2;500:413–426. doi: 10.1016/s0021-9673(00)96082-5. [DOI] [PubMed] [Google Scholar]
- Roboz J., Suzuki R., Holland J. F. Quantification of arabinitol in serum by selected ion monitoring as a diagnostic technique in invasive candidiasis. J Clin Microbiol. 1980 Oct;12(4):594–601. doi: 10.1128/jcm.12.4.594-601.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Soyama K., Ono E. Enzymatic and gas-liquid chromatographic measurement of D-arabinitol compared. Clin Chem. 1988 Feb;34(2):432–432. [PubMed] [Google Scholar]
- Soyama K., Ono E. Enzymatic fluorometric method for the determination of D-arabinitol in serum by initial rate analysis. Clin Chim Acta. 1985 Jul 15;149(2-3):149–154. doi: 10.1016/0009-8981(85)90328-6. [DOI] [PubMed] [Google Scholar]
- Soyama K., Ono E. Improved procedure for determining serum D-arabinitol by resazurin-coupled method. Clin Chim Acta. 1987 Sep 30;168(2):259–260. doi: 10.1016/0009-8981(87)90297-x. [DOI] [PubMed] [Google Scholar]
- TOUSTER O., SHAW D. R. Biochemistry of the acyclic polyols. Physiol Rev. 1962 Apr;42:181–225. doi: 10.1152/physrev.1962.42.2.181. [DOI] [PubMed] [Google Scholar]
- Wong B., Brauer K. L. Enantioselective measurement of fungal D-arabinitol in the sera of normal adults and patients with candidiasis. J Clin Microbiol. 1988 Sep;26(9):1670–1674. doi: 10.1128/jcm.26.9.1670-1674.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wong B., Castellanos M. Enantioselective measurement of the Candida metabolite D-arabinitol in human serum using multi-dimensional gas chromatography and a new chiral phase. J Chromatogr. 1989 Oct 27;495:21–30. doi: 10.1016/s0378-4347(00)82606-7. [DOI] [PubMed] [Google Scholar]