The overall objectives of this project are (1) to study changes in the metabolism of thiamine in animals exposed to potentially hazardous substances, and (2) to perform NMR studies on derivatives derived from the thiazole ring system of the thiamine molecule. At the beginning of this project, an analytical procedure will be devised for the determination of thiamine acetic acid and 4-methylthiazole-5-acetic acid, two metabolic products of thiamine. The metabolic studies will focus on ethanol as a potentially hazardous substance and the relationship of the enzymatic activity of alcohol dehydrogenase to the quantities of specific thiamins metabolites excreted. Underlying the second objective is an attempt to understand the function of the amino group on the pyrimidine ring of thiamine. This project is the first phase of a study designed to correlate a trend in thiamine concentration and its metabolite ratios with the extent of a disturbance in the metabolism of thiamine caused by excessive foreign substances. A study of the spectral properties of thiamine analogs will be continued in an effort to expand man's knowledge of the relationship between the structure of thiamine and Its function In living organisms.
