@article{8f5d55dc905840609b99acb226416d3a,
title = "The unusual inhibition of glutamate dehydrogenase by guanosine di- and triphosphate",
author = "Carl Frieden",
note = "Funding Information: this dissociation may be correlated with the extent of inhibition of DPNH oxidation by high DPNH concentrations s. The presence of GTP or GDP markedly enhances the ability of DPNH to cause dissociation as observed in ultracentrifugation experiments. The ability of GTP to cause dissociation of the enzyme in the presence of TPNH, TPN + or DPN + instead of DPNH is considerably less, although such dissociation does occur. Several important points should be noted about inhibition of glutamate dehydrogenase by guanosine di-and triphosphates: First, inhibition of DPNH oxidation is much greater than TPNH oxidation for a given concentration of inhibitor. This results essentially from the fact that the inhibition constant is lower when using DPNH. Since the inhibition is of an uncompetitive nature, which requires the coenzyme to be bound before the inhibitor, the difference in inhibition constants may reflect the difference between the effect of DPN H and TPN H on the site which binds the GTP or GDP. In addition, the inhibition using DPNH as coenzyme is made even more effective since the inhibitor (GDP or GTP) causes the substrate inhibition by DPNH to occur at much lower levels of DPNH. This explains why the inhibited curves in Fig. 2 bend up so sharply, as compared to the curve without inhibitor. Secondly, DPNH oxidation, especially at higher concentrations, is inhibited to a much greater extent at identical GTP or GDP concentrations than is DPN + reduction. Thus it seems quite possible to affect markedly the rate of reaction in one direction but not in the other. Third, the DPNH data must be explained in terms of a minimum of at least three binding sites of the enzyme for nucleotides, two for DPNH, and the third for the inhibitor (Mechanism I).The argument that one binding site may bind more than one molecule of either coenzyme or nucleotide appears less likely on the basis of previous data, but is not completely ruled out. Finally, it is concluded that the inhibition, particularly the unusual nature of the inhibition by either GTP or GDP using DPNH as coenzyme may be correlated to the reversible association-dissociation reaction of the enzyme itself 2, 3. Further work on this problem is in progress. This research was supported by a Research Grant, RG-8II7, from the National Institutes of Health, U.S. Public Health Service.",
year = "1962",
month = may,
day = "21",
doi = "10.1016/0006-3002(62)90204-4",
language = "English",
volume = "59",
pages = "484--486",
journal = "BBA - Biochimica et Biophysica Acta",
issn = "0006-3002",
number = "2",
}