The object of the proposed research is to elucidate the relationship between polypeptide growth factors, 2-oxocarboxylic acids, NAD-linked oxidoreductases and NAD ion/NADH in regulation of cell multiplication. The effect of growth factors and growth state of the cell on the fate of intra- and extracellular 2-oxocarboxylic acids and the kinetics of influx-efflux of the acids across cell membranes and membrane vesicles will be determined. The effect of growth factors and growth state of cells on the activity of plasma membrane-associated NAD-dependent oxidoreductases will be compared to activity in the cytoplasm and other cell fractions. The effect in disrupted cells of 2-oxocarboxylic acids and NAD ion/NADH on key areas of metabolism that may limit cell division will be studied. These include glucose metabolism, protein synthesis, mucopolysaccharide biosynthesis, cyclic nucleotide metabolism and protein phosphorylation.