GLYCINE, SERINE AND THREONINE METABOLISM

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The goal of this research is to characterize the metabolic regulation of serine, threonine and glycine in mammalian liver tissue and in diseased and normal states. Special emphasis will be placed on the relationship of the enzymes catalyzing committed steps in the catabolism of these amino acids and on the relationship of these enzymes to neogenesis of labile methyl groups. The metabolism of serine, threonine and glycine in mammalian liver tissue will be studied from the standpoint of their interlocking and putative roles on 1-carbon metabolism. Many of these enzymes have as co-factors pyridoxal phosphate and/or folic acid. We will study the mechanism of catalysis by these enzymes. Spectral studies and kinetic studies will enable us to further characterize these reactions. Evidence concerning the distribution and compartmentalization of these enzymes will also be investigated. The role of aminoacetone in metabolism will be investigated. Special attention will be directed towards unraveling the metabolic rate of the carbon atoms of the amino acids; glycine, serine and threonine. The enzymes identified for investigation include, glycine cleavage complex, serine transhydroxymethylase, aminoacetone synthase, and thronine dehydrogenase. A multi-faceted approach will be taken which will include: organic synthesis, enzyme isolation, kinetic measurements and mechanistic studies.