Spach P I, Bottenus R E, Cunningham C C
Biochem J. 1982 Feb 15;202(2):445-52. doi: 10.1042/bj2020445.
Male rats developed fatty liver after being fed on an ethanol-containing diet for 31 days. Liver mitochondria from these animals catalysed ATP synthesis at a slower rate when compared with mitochondria from pair-fed control rats (control mitochondria), and demonstrated lowered respiratory control with succinate as substrate, owing to a decrease in the State-3 respiratory rate. Respiration in the presence of uncoupler was comparable in mitochondria from both groups of rats. Translocation of both ATP and ADP was decreased in mitochondria from ethanol-fed rats, with ADP uptake being lowered more dramatically by ethanol feeding. Parameters influencing adenine nucleotide translocation were investigated in mitochondria from ethanol-fed rats. Experiments performed suggested that lowered adenine nucleotide translocation in these mitochondria is not the result of inhibition of the translocase by either long-chain acyl-CoA derivatives or unesterified fatty acids. Analysis of endogenous adenine nucleotides in these mitochondria revealed lowered ATP concentrations, but no decrease in total adenine nucleotides. In experiments where the endogenous ATP in these mitochondria was shifted to higher concentrations by incubation with oxidizable substrates or defatted bovine serum albumin, the rate of ADP translocation was increased, with a linear correlation being observed between endogenous ATP concentrations and the rate of ADP translocation. The depressed ATP concentration in mitochondria from ethanol-fed rats suggests that the ATP synthetase complex is replenishing endogenous ATP at a slower rate. The lowered ATPase activity of the ATP synthetase observed in submitochondrial particles from ethanol-fed animals suggests a decrease in the function of the synthetase complex. A decrease in the rate of ATP synthesis in mitochondria from ethanol-fed rats is sufficient to explain the decreased ADP translocation and State-3 respiration.
雄性大鼠在给予含乙醇饮食31天后出现脂肪肝。与配对喂养的对照大鼠（对照线粒体）的线粒体相比，这些动物的肝脏线粒体催化ATP合成的速率较慢，并且以琥珀酸为底物时呼吸控制降低，这是由于状态3呼吸速率降低所致。两组大鼠线粒体在解偶联剂存在下的呼吸情况相当。乙醇喂养大鼠的线粒体中ATP和ADP的转运均减少，乙醇喂养使ADP摄取降低得更为显著。对乙醇喂养大鼠的线粒体中影响腺嘌呤核苷酸转运的参数进行了研究。实验表明，这些线粒体中腺嘌呤核苷酸转运降低不是长链酰基辅酶A衍生物或未酯化脂肪酸对转位酶抑制的结果。对这些线粒体中内源性腺嘌呤核苷酸的分析显示ATP浓度降低，但总腺嘌呤核苷酸没有减少。在通过与可氧化底物或脱脂牛血清白蛋白孵育将这些线粒体中的内源性ATP转移到更高浓度的实验中，ADP转运速率增加，内源性ATP浓度与ADP转运速率之间呈线性相关。乙醇喂养大鼠的线粒体中ATP浓度降低表明ATP合成酶复合物补充内源性ATP的速率较慢。在乙醇喂养动物的亚线粒体颗粒中观察到的ATP合成酶的ATP酶活性降低表明合成酶复合物的功能下降。乙醇喂养大鼠的线粒体中ATP合成速率降低足以解释ADP转运和状态3呼吸的降低。
