3- Hydroxypropylmercapturic acid

Sanduja, R., G.A. Ansari, and PJ. Boor. 1989.3-hydroxypropylmercapturic acid a biologic marker of exposure to allylic and related compounds. Jour. Appl. Toxicol. 9 235-238. 

A product of the conjugation of acrolein with glutathione, 3- hydroxypropylmercapturic acid, has been identified in the urine of individuals receiving the drug cyclophosphamide (Alarcon 1976 Kaye and Young 1974). Since the same product was identified in the urine of rats administered acrolein subcutaneously (Alarcon 1976), it was thought that levels of 3-hydroxypropylmercapturic acid in the urine could be used to identify exposure to acrolein. However, Alarcon (1976) found no correlation between the dose of cyclophosphamide administered and the amount of 3-hydroxypropylmercapturic acid in the urine of patients. Methods developed to determine levels of acrolein in human tissues and fluids are described in Chapter 6. 

Biomarkers of Exposure and Effect. No reliable biomarkers of acrolein exposure have been identified. The finding of 3-hydroxypropylmercapturic acid in the urine after exposure to acrolein or cyclophosphamide seemed to be promising for use as an exposure identifier. Flowever, further... 

Alarcon (1976) developed a method for quantifying 3-hydroxypropylmercapturic acid (MCA), a known metabolite of acrolein, in urine. This method involves acidification of the urine to convert MCA to S - (3 - hydroxypropyl) - L - cysteine. The amount of S - (3 - hydroxypropyl) - L - cysteine can then be quantitated using an automated amino acid analyzer. 

Methods for Determining Biomarkers of Exposure and Effect. No biomarker that can be associated quantitatively with exposure of acrolein has been identified (see Section 2.5). There are methods that can detect acrolein as well as its metabolite 3-hydroxypropylmercapturic acid. The methods used for the analysis of acrolein, however, can be susceptible to interferences. Methods that positively identify acrolein or one of its derivatives would eliminate the problems associated with specificity of the technique. 

Alarcon RA. 1976. Studies on the in vivo formation of acrolein. 3-Hydroxypropylmercapturic acid as an index of cyclophosphamide (NSC-26271) activation. Cancer Treat Rep 60 327-335. 

Giles PM. 1979. The biosynthesis of 3-hydroxypropylmercapturic acid from cyclophosphamide. Xenobiotica 9 745-762. 

Draminski et al. (1983) administered 10 mg/kg of acrolein as a single oral dose to rats and collected the urine during 3 days. Since the metabolite S - carboxyethylmercapturic acid was found in the urine, but S - hydroxypropylmercapturic acid (which should have been formed if acrolein had reacted with glutathione) was not, an alternative pathway was proposed. In this metabolic scheme, acrolein is first metabolized to acrylic acid with subsequent formation of the methyl ester, which is then conjugated with glutathione to form S-carboxyethylmercapturic acid methyl ester. The metabolic pathway postulated by Draminski et al. (1983) is shown in Figure 2-4. 

---