PMID: 38961Jun 1, 1979

Activities of NAD-specific and NADP-specific isocitrate dehydrogenases in rat-liver mitochondria. Studies with D-threo-alpha-methylisocitrate

European Journal of Biochemistry
C M Smith, G W Plaut

Abstract

The contributions of NAD-specific and NADP-specific isocitrate dehydrogenases to isocitrate oxidation in isolated intact rat liver mitochondria were examined using DL-threo-alpha-methylisocitrate (3-hydroxy-1,2,3-butanetricarboxylate) to specifically inhibit flux through NADP-specific isocitrate dehydrogenase. Under a range of conditions tested with respiring mitochondria, the rate of isocitrate oxidation was decreased by about 20--40% by inhibition of NADP-isocitrate dehydrogenase, and matrix NADP became more oxidized. (a) For mitochondria incubated with externally added DL-isocitrate and citrate, the rate of isocitrate oxidation obtained by extrapolation to infinite alpha-methylisocitrate concentration was approximately 70% of the uninhibited rate in both state 3 and state 4. (b) With pyruvate plus malate added as substrates of citric acid cycle oxidation and isocitrate generated intramitochondrially, a concentration of alpha-methylisocitrate (400 microM) sufficient for 99.99% inhibition of NADP-isocitrate dehydrogenase inhibited isocitrate oxidation in states 4 and 3 by 21 +/- 6% and 19 +/- 11% (mean +/- SEM), respectively. (c) With externally added isocitrate and citrate, the addition of NH4Cl increased isocitrate oxidation...Continue Reading

References

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Citations

Aug 1, 1976·European Journal of Biochemistry·E LenartowiczA B Wojtczak
Mar 1, 1976·Biophysical Journal·A WilkinsonW Lund
Jun 28, 1973·Biochimica Et Biophysica Acta·J B HoekL ERNSTER
Jan 1, 1964·Biochemical and Biophysical Research Communications·B KadenbachM Klingenberg
Aug 23, 1967·Biochemical and Biophysical Research Communications·G W Plaut, T Aogaichi
Sep 1, 1969·The Biochemical Journal·P B Nicholls DG RAND
Oct 27, 1970·Biochimica Et Biophysica Acta·R A Chamalaun, J M Tager
Apr 8, 1969·Biochimica Et Biophysica Acta·R KraaijenhofK van Dam
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Nov 1, 1957·Biochimica Et Biophysica Acta·L ERNSTER, F NAVAZIO
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Related Concepts

Mitochondria, Liver
NADH
Ketoglutaric Acids
Isocitrate Dehydrogenase-I
NADP
Oxygen Consumption
Ammonium Chloride
Citric Acid Cycle
Isocitrates
Ogdh

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