A structural gene for the DPN-specific glutamate dehydrogenase in Neurospora.

PART from the TPN (triphosphopyridine nucleotide) -specific glutamate deA hydrogenase (T-GDH) first described by FINCHAM ( 1950, 195 l ), Neurospora crassa possesses a DPN (diphosphopyridine nucleotide) -specific glutamate dehydrogenase (D-GDH) which is present ( SANWAL and LATA 1961 a) both in wild-type strains (SANWAL and LATA 1961b) and in mutants lacking T-GDH (am-1 mutants). The presence of D-GDH provides an explanation for the commonly observed leakiness of all am-1 mutants. It has been demonstrated (SANWAL and LATA 1962a,b) that during growth on minimal medium supplemented with glutamate (or other nitrogenous compounds which are easily converted in uiuo to glutamate) active T-GDH of wild-type cells or an antigenically cross-reacting material corresponding to T-GDH of am-1 mutants (SANWAL and LATA 1962c) is repressed and D-GDH is derepressed. Indeed, all environmental conditions which lead to a repression of T-GDH invariably also lead to a derepression of D-GDH. This coupled regulation of two enzymes has been labelled “concurrent regulation” to distinguish it from other types of regulation, such as coordinate (AMES and GARRY 1959) and multivalent ( FREUNDLICH, BURNS and UMBARGER 1962) regulation. The concurrent regulation of T-GDH and D-GDH of Neurospora is strikingly similar to the so-called ‘compensatory’ regulation of 7and ,&chains of hemoglobin during fetal development. Thus, it has been demonstrated that as hemoglobin-F levels fall in the growing embryo the hemoglobin-A levels increase correspondingly till, soon after birth, it becomes the only major component of the normal blood (CHERNOFF and SINGER 1952; ZUCKERBANDL 1964). Based on the operon theory of JACOB and MONOD (1961 ) , a genetic model for the regulation of the hemoglobin varieties has been recently proposed (ZUCKERKANDL 1964), which with certain modifications may equally well be applicable to the regulation of glutamate dehydrogenases of Neurospora. As a first step in our efforts to understand the genetic basis of the concurrent regulation of D-GDH and T-GDH, we present in the following report the isolation and characterization of mutants producing catalytically defective varieties of D-GDH.