Brass E P, Hoppel C L
Biochem J. 1980 Sep 15;190(3):495-504. doi: 10.1042/bj1900495.
The relationship between the acid-soluble carnitine and coenzyme A pools was studied in fed and 24-h-starved rats after carnitine administration. Carnitine given by intravenous injection at a dose of 60mumol/100g body wt. was integrated into the animal's endogenous carnitine pool. Large amounts of acylcarnitines appeared in the plasma and liver within 5min of carnitine injection. Differences in acid-soluble acylcarnitine concentrations were observed between fed and starved rats after injection and reflected the acylcarnitine/carnitine relationship seen in the endogenous carnitine pool of the two metabolic states. Thus, a larger acylcarnitine production was seen in starved animals and indicated a greater source of accessible acyl-CoA molecules. In addition to changes in the amount of acylcarnitines present, the specific acyl groups present also varied between groups of animals. Acetylcarnitine made up 37 and 53% of liver acid-soluble acylcarnitines in uninjected fed and starved animals respectively. At 5min after carnitine injection hepatic acid-soluble acylcarnitines were 41 and 73% in the form of acetylcarnitine in fed and starved rats respectively. Despite these large changes in carnitine and acylcarnitines, no changes were observed in plasma non-esterified fatty acid or beta-hydroxybutyrate concentrations in either fed or starved rats. Additionally, measurement of acetyl-CoA, coenzyme A, total acid-soluble CoA and acid-insoluble CoA demonstrated that the hepatic CoA pool was resistant to carnitine-induced changes. This lack of change in the hepatic CoA pool or ketone-body production while acyl groups are shunted from acyl-CoA molecules to acylcarnitines suggests a low flux through the carnitine pool compared with the CoA pool. These results support the concept that the carnitine/acid-soluble acylcarnitine pool reflects changes in, rather than inducing changes in, the hepatic CoA/acyl-CoA pool.
在给予肉碱后,对喂食和饥饿24小时的大鼠体内酸溶性肉碱和辅酶A池之间的关系进行了研究。以60μmol/100g体重的剂量静脉注射肉碱后,其被整合到动物的内源性肉碱池中。注射肉碱后5分钟内,血浆和肝脏中出现了大量的酰基肉碱。注射后,喂食和饥饿大鼠的酸溶性酰基肉碱浓度存在差异,这反映了两种代谢状态下内源性肉碱池中酰基肉碱/肉碱的关系。因此,饥饿动物体内酰基肉碱的产量更高,这表明可利用的酰基辅酶A分子来源更多。除了酰基肉碱含量的变化外,不同动物组中存在的特定酰基也有所不同。在未注射的喂食和饥饿动物中,乙酰肉碱分别占肝脏酸溶性酰基肉碱的37%和53%。注射肉碱后5分钟,喂食和饥饿大鼠肝脏中酸溶性酰基肉碱分别有41%和73%以乙酰肉碱的形式存在。尽管肉碱和酰基肉碱发生了这些巨大变化,但喂食或饥饿大鼠的血浆非酯化脂肪酸或β-羟基丁酸浓度均未观察到变化。此外,对乙酰辅酶A、辅酶A、总酸溶性辅酶A和酸不溶性辅酶A的测量表明,肝脏辅酶A池对肉碱诱导的变化具有抗性。在酰基从酰基辅酶A分子转移到酰基肉碱的过程中,肝脏辅酶A池或酮体生成没有变化,这表明与辅酶A池相比,通过肉碱池的通量较低。这些结果支持了这样一种观点,即肉碱/酸溶性酰基肉碱池反映了肝脏辅酶A/酰基辅酶A池的变化,而不是诱导其变化。