Evaluation of ischemic damage to rat liver mitochondria using the Krebs-cycle

Pyruvate catabolism is directed towards citrate condensation rather than ketonebody formation both in normal and in ischemic rat liver mitochondria in the presence of an ADP generating system and l-malate. Although the phosphorylating capacity of ischemic liver mitochondria is greatly reduced, their ability to utilize the Krebscycle pathway for energy production is not impaired. Indeed, both in the normal and the ischemic liver mitochondria, the same intermediates—citrate and malate—accumulated and the same concentration of malate inhibited ketogenesis from pyruvate. The degree of impairment in the phosphorylating capacity of stored liver mitochondria utilizing the whole Krebs-cycle gave results similar to those obtained using a single substrate. By both methods, the amount of high-energy phosphate bonds formed by mitochondria of livers stored at 37°C for one hour was less than 50% of normal. It is concluded that under the in vitro conditions of the experiment, the rate limiting steps in the Krebs-cycle are the same for both normal and ischemic rat liver mitochondria.