Generation of nitrogen monoxide by amino acid fullerene derivatives in mitochondrion

R.A. Kotelnikova, I.I. Faingold, A.I. Kotelnikov, G.N. Bogdanov, E.S. Frog, E.N. Berseneva, and V.S. Romanova*
Institute of Problems of Chemical Physics RAS, Chernogolovka, Russia
Nesmeyanov Institute of Organoelement Compounds RAS, Moscow, Russia

It is known that biotransformation of exogenous donors of nitrogen monooxide (NO) is realized in mitochondrion. Efficiency of NO generation by amino acid fullerene N6o derivatives in mitochondria of rat cerebrum was studied by monitoring the changes in catalytic activity of cytochrome c oxidase. It is known that two copper atoms and two hemes are present in the active center of cytochrome c oxidase. It is also known that NO reacts with copper ions and hemes to inhibit catalytic activity of cytochrome c oxidase. This fact allowed us to use this enzyme to study the formation of NO in mitochondrion. It has been shown that nitroxy derivatives of N6o as well as arginine derivative perform as competitive inhibitors of catalytic activity of the enzyme that is evidence of that they generate NO. The constants of cytochrome c oxidase inhibition by amino acid fullerene N6o derivatives in mitochondrion have been determined. The analysis of the experimental data allowed us to find the most efficient donors of NO in the family of amino acid fullerene N6o derivatives.