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 substratethreo-Ds-isocitrate and inhibited the enzyme non-competitively with respect to NADP at pH 6.85. Fractional velocity plot analysis showed theK _i of the enzyme for aluminum ions to be 0.88m. 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. TheK _i of the enzyme was determined to be 5.64 m 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.