Inhibition by alloxan of mitochondrial aconitase and other enzymes associated with the citric acid cycle

FEBS Letters

Boquist, L.¹  Ericsson, I.¹ 

[1] Institute of Pathology and Department of Biochemistry, University of Umeå, S-901 87 Umeå, Sweden

关键词: Aconitase;    Alloxan;    Citric acid cycle;    Enzyme;    Mitochondria;   

DOI  :  10.1016/0014-5793(84)80609-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Considerable variations were found in the in vitro effect of alloxan on mouse liver enzymes associated with the citric acid cycle. The following approximative alloxan concentrations induced 50% inhibition of enzyme activity: 10⁻⁶ M for aconitase, 10⁻⁴ M for NAD-linked isocitrate dehydrogenase, glutamate dehydrogenase, α-ketoglutarate dehydrogenase, succinyl-CoA synthetase and fumarase, and 10⁻³ M for citrate synthase and NADP-linked isocitrate dehydrogenase. Pyruvate dehydrogenase, succinate dehydrogenase and malate dehydrogenase were not inhibited by 10⁻³ M alloxan. The inhibition of aconitase was competitive both when using mouse liver and purified porcine heart enzyme. The K _i values for the purified enzyme in the presence of 5 μM alloxan were 0.22 μM with citrate, 4.0 μM with cis-aconitate and 0.62 μM with isocitrate as substrate. The high sensitivity of aconitase for inhibition by alloxan probably plays a prominent role for the toxic effects of alloxan.

【 授权许可】

Unknown