Annu. Rev. Plant. Physiol. 1961.12:1-13 (5), with collaborators, made the important discovery that glutamic acid dehydrogenase is specific for L glutamic acid and that the reaction catalyzed by it is reversible: L-glutamic acid;::: : a-ketoglutaric acid -\-NHa The first step in reductive amination, i.e., the combining of ammonia with a-ketoglutaric acid, is not well understood even yet, but the first prod uct was assumed to be (�.iminoglutaric acid, which is then reduced by glutamic acid dehydrogenase to L-glutamic acid. This enzyme was found in all kinds of organisms: microorganisms, higher plants, and animal tissues. Later studies confirmed its decisive importance for the biosynthesis of L glutamic add. Knoop's idea of amino acid synthesis was thus realized in_ regard to L-glutamic acid, but at the same time it became evident that it was not a reaction that could explain the biosynthesis of the many different amino acids.Two amino acids in which the amino group is formed through incorpora tion of an inorganic nitrogen compound into the carbon skeleton were thus established with certainty by the end of the 1930's. I have used the term "primary" for amino acids of this type; hence "secondary" amino acids refer to either those in which the precursor already contains the amino (or imino) group, or those to which the amino group is transferred from another com pound.The synthesis of other amino acids by an analogous mechanism was not known with certainty until quite recently, even though some evidence of the "primary" nature of alanine was presented earlier. In a scheme showing the synthesis of amino acids, ten years ago I used an arrow marked with a solid line for the biosynthesis of glutamic and aspartic acids from ammonia and an arrow marked with a broken line for alanine (6). The broken line how ever, can now be drawn as a solid one since Goldman (7) recently isolated and purified from a cell-free extract of Mycobacterium tuberculosis an alanine dehydrogenase which catalyses the reaction: L-alanine+DPN+�pyruvate +NH4++DPNH.It is probable that the mechanism of action of glutamic and alanine de hydrogenases is similar. An analogous mechanism has been proposed for some other amino acids, e.g., L-aspartic acid from oxalacetic acid and am monia, but the enzyme preparations used were not purified and the reaction could not be sufficiently studied (8). Reductive amination of a-ketovaleric acid to L-norvaline, an amino acid which has never been found in higher organisms, has recently been carried out however, by crystalline glutamic acid dehydrogenase from liver (9). This reaction is possibly of no great bio logical significance, but from the biochemical point of view it is interesting, because it indicates that the 'Y-carboxyl group in a-ketoglutaric acid is not essential for the functioning of the enzyme.Even if in some organisms alanine may be formed primarily from am monia by alanine dehydrogenase, there is no proof that this amino acid