Björkhem I
J Biol Chem. 1976 Sep 10;251(17):5259-66.
The stimulatory effect of starvation on omega oxidation of stearate by the 20,000 X g supernatant fluid of rat liver homogenates was studied. The effect was obtained after starvation for 24 hours. Starvation for longer times did not further increase omega oxidation. The stimulatory effect of starvation on omega oxidation of stearic acid was accompanied by a reduced incorporation of stearic acid into phosphatidic acid, diglycerides, and triglycerides. Substitution of the 100,000 X g supernatant fluid from liver homogenate of starved rats with 100,000 X g supernatant fluid from liver homogenates of control rats reduced the microsomal omega oxidation of stearic acid with a simultaneous increase in incorporation of stearic acid into the different glycerides. Under the latter conditions almost no free stearic acid could be isolated from the incubation mixture after the incubation. Of three different soluble factors necessary for glyceride formation, ATP appeared to be the most important from a regulatory point of view. Thus the soluble fraction of liver homogenate from a starved rat was shown to contain suboptimal concentrations of ATP. Addition of physiological amounts of ATP to the 20,000 X g supernatant fluid of homogenate of liver of starved rats had the same effect as addition of 100, 000 X g supernatant fluid from liver homogenate of control rats, i.e. decrease in omega oxidation and increase in formation of glycerides. Addition of sn-glycerol 3-phosphate and CoA-SH in amounts optimal for glyceride formation to the 20,000 X g supernatant fluid of liver homogenate of starved rats had only small effects on omega oxidation and glyceride formation. The results are consistent with a competition for free fatty acids between the acyl-CoA synthetases involved in biosynthesis of glycerides and the microsomal hydroxylase(s) involved in omega oxidation of fatty acids. The concentration of ATP in the soluble fraction is of importance in this competition. The possibility is discussed that this competition is of importance also under in vivo conditions and that a decreased rate of esterification in the starved state is responsible for the higher excretion of omega-oxidized fatty acids in urine in the ketotic state.
研究了饥饿对大鼠肝脏匀浆20,000×g上清液中硬脂酸ω氧化的刺激作用。饥饿24小时后出现该效应。饥饿更长时间并未进一步增加ω氧化。饥饿对硬脂酸ω氧化的刺激作用伴随着硬脂酸掺入磷脂酸、甘油二酯和甘油三酯的减少。用对照大鼠肝脏匀浆的100,000×g上清液替代饥饿大鼠肝脏匀浆的100,000×g上清液，可降低硬脂酸的微粒体ω氧化，同时硬脂酸掺入不同甘油酯的量增加。在后一种条件下，孵育后几乎无法从孵育混合物中分离出游离硬脂酸。在甘油酯形成所需的三种不同可溶性因子中，从调节角度来看，ATP似乎是最重要的。因此，饥饿大鼠肝脏匀浆的可溶性部分显示含有次优浓度的ATP。向饥饿大鼠肝脏匀浆的20,000×g上清液中添加生理量的ATP，其效果与添加对照大鼠肝脏匀浆的100,000×g上清液相同，即ω氧化减少，甘油酯形成增加。向饥饿大鼠肝脏匀浆的20,000×g上清液中添加对甘油酯形成最适宜量的sn-甘油3-磷酸和辅酶A-SH，对ω氧化和甘油酯形成的影响很小。这些结果与参与甘油酯生物合成的酰基辅酶A合成酶和参与脂肪酸ω氧化的微粒体羟化酶之间对游离脂肪酸的竞争一致。可溶性部分中ATP的浓度在这种竞争中很重要。讨论了这种竞争在体内条件下也很重要的可能性，以及饥饿状态下酯化速率降低是酮症状态下尿液中ω氧化脂肪酸排泄增加的原因。
