Inhibition of NADP-dependent dehydrogenases by modified products of NADPH

• Published in: Archives of biochemistry and biophysics Vol. 169; no. 1; pp. 298 - 303
• Main Authors: Yoshida, Akira, Dave, Vibha
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.1975
• Subjects: Binding, Competitive; Glucosephosphate Dehydrogenase - antagonists & inhibitors; Hydrogen-Ion Concentration; Kinetics; NADH, NADPH Oxidoreductases - antagonists & inhibitors; NADP - analogs & derivatives; NADP - pharmacology; Phosphogluconate Dehydrogenase - antagonists & inhibitors; Spectrum Analysis
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/0003-9861(75)90344-6

When NADPH was incubated at neutral pH, a modified product which had no absorbancy at 340 nm, but exhibited a slight shoulder in the region of 280–300 nm with maximum absorbancy at 266 nm, was produced. Phosphate accelerated the conversion. This compound was tentatively designated as NADPH-X. At acidic pH, NADPH was rapidly converted to the primary acid-modified product which had a similar, but not identical, absorption spectrum to that of NADPH-X, and it was gradually converted to the secondary acid-modified product which exhibited a distinctive absorption spectrum with a maximum at 261 nm. NADPH-X strongly inhibited human glucose 6-phosphate dehydrogenase, human 6-phosphogluconate dehydrogenase, and yeast glucose 6-phosphate dehydrogenase. The primary acid-modified product inhibited human 6-phosphogluconate dehydrogenase, but human and yeast glucose 6-phosphate dehydrogenases were not sensitive to this compound. The secondary acid-modified product inhibited the three dehydrogenases. The mode of the dehydrogenase inhibition by these compounds was competitive with NADP. Potential physiologic role of NADPH-X was discussed.