ミトコンドリアを中心とせる肝障害の生化学的研究

抄録

We investigated the mechanism of the liver damage due to CC1₄ poisoning, especially concerning the mitochondrial functions, i. e. the capacity of oxidative phosphorylation and the respiratory enzyme activities, in relation to the optical properties, constituents and structure of mitochondria.
1. The reduction of P: O ratio occurred in acute poisoning in a day after injection of CC1₄, and recovered to normal level after 1 week. But this change was limited to the D.P.N. -linked reactions by use of α-ketoglutarate or pyruvate as a substrate, and when succinate was used as a substrate, we could not find any reduction of P: O ratio. V.E. protected completely the lowering of P: O ratio.
2. Succinate-Cyt. C. reductase and Cyt. oxidase activities tended to decrease slightly in the damaged liver, but DPN-Cyt. C. reductase activity clearly increased, suggesting the possible changes of mitochondrial structure.
3. Swelling of damaged liver mitochondria caused by orthophosphate, estimated by the reduction of optical density of mitochondrial suspensions, is less remarkable than that of the normal, and in other conditions we could find some differences between normal and damaged liver mitochondria. Light scattering method revealed difference of the degree of asymmetry at 45° between the suspensions of the normal and damaged liver mitochondria.
4. Lipid: total N, cholesterol and fatty acetals: fatty acid ester groups in the lipids of mitochondrial fraction increased in the CC1₄ poisoning, and acetals per mito chondria eq. to one gram liver increased markedly in the chronic poisoning. Both iodine value of lipids and peroxide formation of mitochondria, estimated by T.B.A. reaction, decreased. P³²O₄ incorporation into the lipids of mitochondrial fraction is markedly diminished.
5. From the results above reported we concluded that CC1₄ damaged liver mitochondria primarily, changed their structure, thus leading to the lowering of the capacity of energy utilization. The changes in the lipid constituents of mitochondria seemed to have any relationship to these dysfunctions.