Control of the citric acid cycle by glyoxylate. The mechanism of inhibition of oxoglutarate dehydrogenase, isocitrate dehydrogenase and aconitate hydratase.
1. The effects of glyoxylate on partially purified preparations of aconitate hydratase, isocitrate dehydrogenase and oxoglutarate dehydrogenase were compared with those of oxalomalate and hydroxyoxoglutarate (obtained by condensation of glyoxylate with oxaloacetate and pyruvate respectively). 2. Glyoxylate (1mm) did not affect aconitate hydratase and isocitrate dehydrogenase, whereas oxalomalate (1mm) inhibited the enzyme activities completely. 3. Glyoxylate (0.025mm) inhibited oxoglutarate dehydrogenase irreversibly, whereas the same concentrations of oxalomalate and hydroxyoxoglutarate were ineffective. This inhibitory effect was prevented if oxoglutarate, pyruvate or oxaloacetate was mixed with the enzyme before the glyoxylate. 4. Incubation of oxoglutarate dehydrogenase with radioactive glyoxylate produced radioactive carbon dioxide; radioactivity was also recovered in the portion of the enzyme identified with thiamin pyrophosphate. 5. The behaviour of glyoxylate in producing multiple inhibitions of the citric acid cycle, either by direct interaction with oxoglutarate dehydrogenase, or by means of its condensation compounds which inhibit aconitate hydratase and isocitrate dehydrogenase, is discussed.
D000818:Animals; D002245:Carbon Dioxide; D002247:Carbon Isotopes; D002952:Citric Acid Cycle / Q000187:drug effects; D005977:Glutarates; D006038:Glyoxylates / Q000494:pharmacology*; D006836:Hydro-Lyases / Q000037:antagonists & inhibitors*; D007521:Isocitrate Dehydrogenase / Q000037:antagonists & inhibitors*; D008293:Malates; D010071:Oxaloacetates; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011773:Pyruvates; D013552:Swine; D013835:Thiamine Pyrophosphate
D002247:Carbon Isotopes; D005977:Glutarates; D006038:Glyoxylates; D008293:Malates; D010071:Oxaloacetates; D011773:Pyruvates; D002245:Carbon Dioxide; D010088:Oxidoreductases; D007521:Isocitrate Dehydrogenase; D006836:Hydro-Lyases; D013835:Thiamine Pyrophosphate
Biochem Biophys Res Commun. 1966 Jun 13;23(5):585-91
5963883
J Biol Chem. 1965 May;240:2135-41
14299638
Biochem J. 1967 Mar;102(3):885-97
16742506
Biochem J. 1967 Sep;104(3):50P-51P
6049883
J Biol Chem. 1953 Oct;204(2):565-75
13117830
Biochem J. 1967 Apr;103(1):19-23
6033757
J Biol Chem. 1952 May;197(2):851-62
12981117
Biochem J. 1962 Dec;85:588-93
13983203