Effects of a set of a-ketoglutarate phosphoanalogues on the activity of a-ketoglutarate dehydrogeoase (EC 1.2.4.2) complexes from E. coli and pigeon breast muscle, as well as on aketoglutarate dehydrogeoase isolated from the pigeon breast muscle, have been studied, a-Ketoglutarate phosphoanalogues (sueeinyl phosphonate and its monomethyl ester) were found to be effective inhibitors of a-ketoglutarate oxidative decarboxylationt catalyzed by both nmsde and bacterial a-ketuglutarate dehydrogenase complexes, as well as muscle a-ketoglutarate dehydrogenase. The ability of glutamate phosphoanalogues to Inhibit a-ketoglutarate oxidative decarboxylation has been shown in F.. coil extract and a model system. [6][7][8][9]. The feature of inhibition of pyruvate dehydrogenase was investigated by phosphoanalogaes of Pyr, modified at phosphorus containing fragment [5].In this work we have studied the effect of a set of a-Kglu phosphoanalogues (succinyl phosphonate, Sue-P, and appropriate esters) on the activity of a-ketoglutarate dehydrogenase complexes (a-KGDC) from E. coli and pigeon breast muscle, as well as on a-KGD isolated from the pigeon breast muscle. In addition, we have studied the possibility of metabolic transformation of the glutamate phosphoanalogues, l-amino-3-carboxypropyiphosphonic (Glu-P) and -phosphinic (Glu-P.) acids into dehydrogenase inhibitors in a model system and extract of E. coli.

Succinylphosphonate (SP) is a powerful inhibitor of a-ketoglutarate dehydrogcnase (KGD). Methylation of the phosphonate reduces its inhibitory effect. The complex of KGD with SP undergoes a kinetically slow transition similar to the process observed during catalysis. +Ketoglutnrate binds to the enzyme-inhibitor complex, preventing its isomerisation.o-Ketoglutarate dchydrogcnase; Transition state analogue; Succinylphosphonate; Slow isomcrisation

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Well-known aminaacyl-tRNA synthetase (ARSase) inhibitors, namely the analogues of amino acids and aminoacyl adenylates (atninoalkyl-and aminophosphonyl adenylates with K, ~0.1 ,uM) as well as the diadenosine 5',5"'-pi,@-tetraphospbate (Ap&A) phosphonoanalogues, were for the first time used for the Ap,A biosynthesis regulation. Effects of a set of such compounds on lysyl-, phenylalanyl-and alanyl-tRNA synthetases from E. coli, capable of synthesizing Ap,A in the presence of Zn2' ions and pyrophosphatase, have been studied. The adenylate analogues were found to inhibit the Ap,A and Ap,A formation (I,, ~6 mM). Aminophasphonic and aminophosphonous acids are not involved in Ap,A and Ap+A biosynthesis and inhibited it at high concentrations. The Ap,A phospboanalogues slightly inhibited the major reactions of ARSases, as well as the biosynthesis ofA&A and Ap,A, at a concentration of 5 mM.

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