Department of Clinical Chemistry, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
J Inherit Metab Dis. 2010 Oct;33(5):469-77. doi: 10.1007/s10545-010-9061-2. Epub 2010 Mar 2.
Over the years, the mitochondrial fatty acid β-oxidation (FAO) pathway has been characterised at the biochemical level as well as the molecular biological level. FAO plays a pivotal role in energy homoeostasis, but it competes with glucose as the primary oxidative substrate. The mechanisms behind this so-called glucose-fatty acid cycle operate at the hormonal, transcriptional and biochemical levels. Inherited defects for most of the FAO enzymes have been identified and characterised and are currently included in neonatal screening programmes. Symptoms range from hypoketotic hypoglycaemia to skeletal and cardiac myopathies. The pathophysiology of these diseases is still not completely understood, hampering optimal treatment. Studies of patients and mouse models will contribute to our understanding of the pathogenesis and will ultimately lead to better treatment.
多年来,线粒体脂肪酸 β-氧化 (FAO) 途径已在生化和分子生物学水平上得到了描述。FAO 在能量稳态中起着关键作用,但它与葡萄糖竞争作为主要氧化底物。这种所谓的葡萄糖-脂肪酸循环的机制在激素、转录和生化水平上运作。大多数 FAO 酶的遗传缺陷已被确定和描述,并已纳入新生儿筛查计划。症状从低酮性低血糖到骨骼和心肌病变不等。这些疾病的病理生理学尚未完全了解,这妨碍了最佳治疗。对患者和小鼠模型的研究将有助于我们了解发病机制,并最终导致更好的治疗。