The biosynthesis of serine in mouse brain extracts.

In certain species of bacteria there is one major route for the biosynthesis of serine from glucose (1, 2). The pathway branches from glycolgsis at nglycerate 3-O-phosphate (glycerate-P) with a nicotinamide adenine dinucleotide-dependent oxidation yielding hydroxypyruvate phosphate (hydroxypyruvate-P). Transamination of this intermediate with glutamate yields L-serine 3-O-phosphate (serine-P), the immediate precursor of serine. The same pathway was postulated to occur in rat liver (3), however, little glycerate-1’ dehydrogenase has been demonstrated in this tissue in adult rats on a laboratory ration’ (4, 5). Another mammalian pathway to serine involving t,he nonphosphorylated intermediates u-glycerate and hydroxypyruvate has also been proposed (6, 7); however, no quantitative studies of the relative importance of the two routes, referred to as the phosphorylated and nonphosphorylated pathways, have been reported. A recent survey of normal tissues did show that adult rat liver contained much higher levels of u-glycerate dehydrogenase than of glycerate-l’ dehydrogenase (5). These results might suggest that the nonphosphorylated pathway is the preferred route for synthesis of serine in rat liver. However, adult rat’ liver contains an active serine-I’ phosphatase (8, 9), and to date no role for serine-P other t,han as a precursor of serine has been found. It would appear that definitive studies required for elucidation of a major route to serine in a mammalian tissue have not been reported. Pizer (10) has shown that the phosphorylated pat,hway is operative in cultured human KB cells, and that enzymes in the pathway are subject bo a repression-like phenomenon when the cells are grown in t’he presence of exogenously supplied serine. It is not possible to determine from these experiments whether this pathway is the only or major route to serine in these cells. The experiments reported here demonstrate t’hat a cell-free extract, of adult mouse brain (San synthesize serine from glucose. Glycerate-P and serine-P are intermediates, and the evidence obtained supports the presence of the phosphorylated route as the major pat,hway to serine from glucose in this preparation.