Aluminum: a pH-dependent inhibitor of NADP-isocitrate dehydrogenase from porcine heart.

Aluminum showed a pH-dependent inhibitory effect on NADP-isocitrate dehydrogenase from porcine heart. Aluminum ions (Al3+) acted as a partial competitive inhibitor of the enzyme with respect to the substrate threo-Ds-isocitrate and inhibited the enzyme non-competitively with respect to NADP at pH 6.85. Fractional velocity plot analysis showed the Ki of the enzyme for aluminum ions to be 0.88 microM. When pH was elevated to 8.0, aluminum ions, which occur as a form of the Al(OH)4- anion, acted as partial uncompetitive and non-competitive inhibitors of the enzyme with respect to the substrates isocitrate and NADP, respectively. The Kí of the enzyme was determined to be 5.64 microM at pH 8.0 by fractional velocity plot analysis. The inhibition of NADP-isocitrate dehydrogenase by two forms of aluminum ions may explain aluminum toxicity in various tissues and organs.