O'Connor J E, Costell M
Instituto de Investigaciones Citológicas de la Caja de Ahorros de Valencia, Centro Asociado del CSIC, Spain.
Adv Exp Med Biol. 1990;272:183-95. doi: 10.1007/978-1-4684-5826-8_12.
High levels of ammonia in blood and brain due to metabolic disorders are associated with neurological abnormalities. Although the mechanism of ammonia toxicity at the CNS level is still unknown, alterations in brain energy metabolism, in neurotransmitter function and direct effects on nervous impulse have been proposed. In most hyperammonemic conditions morphological changes in the liver and brain have been demonstrated, especially in mitochondria, endoplasmic reticulum and lysosomes, together with an accumulation of intracellular lipids. The treatment of hyperammonemias is uncertain and mostly directed to reduce the level of circulating ammonia; there is no current therapy aimed to counteract the molecular effects of ammonia. Administration of carnitine prevents acute ammonia toxicity and enhances the efficacy of ammonia elimination as urea and glutamine. In addition the cytotoxic effects of ammonia, possibly arising from lipid peroxidation, are ameliorated by carnitine. These data indicate the feasibility of utilization of carnitine in the therapy of human hyperammonemic syndromes, both for reducing the levels of ammonia and preventing its toxic effects.
代谢紊乱导致血液和大脑中氨水平升高与神经功能异常有关。尽管中枢神经系统水平的氨毒性机制尚不清楚，但有人提出脑能量代谢、神经递质功能改变以及对神经冲动的直接影响。在大多数高氨血症情况下，肝脏和大脑已出现形态学变化，尤其是线粒体、内质网和溶酶体，同时伴有细胞内脂质积累。高氨血症的治疗尚不确定，主要旨在降低循环氨水平；目前尚无旨在对抗氨分子效应的疗法。肉碱给药可预防急性氨毒性，并提高氨以尿素和谷氨酰胺形式消除的功效。此外，肉碱可改善可能由脂质过氧化引起的氨的细胞毒性作用。这些数据表明，肉碱用于治疗人类高氨血症综合征以降低氨水平并预防其毒性作用是可行的。
