PMID: 36073Mar 1, 1979

Inhibitory effects of histidine and their reversal. The roles of pyruvate carboxylase and N10-formyltetrahydrofolate dehydrogenase

The Biochemical Journal
M C Scrutton, I Beis

Abstract

1. N10-Formyltetrahydrofolate dehydrogenase was purified to homogeneity from rat liver with a specific activity of 0.7--0.8 unit/mg at 25 degrees C. The enzyme is a tetramer (Mw = 413,000) composed of four similar, if not identical, substrate addition and give the Km values as 4.5 micron [(-)-N10-formyltetrahydrofolate] and 0.92 micron (NADP+) at pH 7.0. Tetrahydrofolate acts as a potent product inhibitor [Ki = 7 micron for the (-)-isomer] which is competitive with respect to N10-formyltetrahydrofolate and non-competitive with respect to NADP+. 3. Product inhibition by NADPH could not be demonstrated. This coenzyme activates N10-formyltetrahydrofolate dehydrogenase when added at concentrations, and in a ratio with NADP+, consistent with those present in rat liver in vivo. No effect of methionine, ethionine or their S-adenosyl derivatives could be demonstrated on the activity of the enzyme. 4. Hydrolysis of N10-formyltetrahydrofolate is catalysed by rat liver N10-formyltetrahydrofolate dehydrogenase at 21% of the rate of CO2 formation based on comparison of apparent Vmax. values. The Km for (-)-N10-folate is a non-competitive inhibitor of this reaction with respect to N10-formyltetrahydrofolate, with a mean Ki of 21.5 micron for...Continue Reading

Citations

Dec 1, 1987·Blood Reviews·P P Weinstein, J J Jaffe
Jul 22, 2010·Annual Review of Nutrition·Anne S Tibbetts, D R Appling
Oct 14, 2008·Chemico-biological Interactions·Sergey A Krupenko
May 4, 1993·Biochemistry·L F García-Martínez, D R Appling
Apr 15, 1981·Archives of Biochemistry and Biophysics·R E BillingsT R Tephly
Jan 13, 1995·The Journal of Biological Chemistry·Sergey A KrupenkoR J Cook
Jan 1, 2008·Nutrition Research and Practice·Ju-Ae MunHyesun Min
Mar 14, 2000·The Journal of Biological Chemistry·J TangH R Herschman
Oct 9, 1998·The Journal of Biological Chemistry·S KimK R Williams
Apr 22, 2009·Expert Review of Molecular Diagnostics·József Gábor Joó
Sep 22, 2007·The Journal of Biological Chemistry·Henry DonatoSergey A Krupenko

Related Concepts

Oxidoreductases Acting on CH-NH Group Donors
Formiminoglutamic Acid
N(10)-Formyltetrahydrofolate
Histidine
Liver
NADP
Pyruvate Carboxylase
Drug or Chemical Tissue Distribution

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