Oey Nadia A, Ruiter Jos P N, Attié-Bitach Tania, Ijlst Lodewijk, Wanders Ronald J A, Wijburg Frits A
Department of Pediatrics, G8-205, Emma Children's Hospital AMC, Academic Medical Centre, PO Box 22660, NL-1100 DD, Amsterdam, The Netherlands.
J Inherit Metab Dis. 2006 Feb;29(1):71-5. doi: 10.1007/s10545-006-0199-x.
Studies in the last few years have shown a remarkably high activity of fatty acid oxidation (FAO) enzymes in human placenta. We have recently shown mRNA expression as well as enzymatic activity of long-chain FAO enzymes in the human embryo and fetus. In this study we show activity of the FAO enzymes carnitine palmitoyltranferase 1, medium-chain acyl-CoA dehydrogenase and short-chain hydroxyacyl-CoA dehydrogenase in embryonic and fetal tissues. In addition, we show the presence of different acylcarnitines in fetal liver and kidney, which substantiates the notion that the mitochondrial FAO enzymes are not only present in human fetal tissues but also metabolically active. In a glucose-rich environment FAO might be necessary for additional ATP production from fatty acids, but also for the breakdown of fatty acids that are products of the turnover of membranes in the growing fetus. The importance of FAO in the human embryo and fetus is further stressed by the fact that a higher frequency of prematurity, intrauterine growth retardation, fetal morbidity and intrauterine death is noted in long-chain FAO defects. Furthermore, in animal studies, gestational loss during early embryonic development has been observed as a consequence of disturbed FAO. Finally, there are indications that regulation of activity of FAO during fetal development might not only be important for fetal life but may also have implications for health and disease in adulthood.
过去几年的研究表明，人胎盘组织中脂肪酸氧化（FAO）酶的活性异常高。我们最近发现，长链FAO酶在人类胚胎和胎儿中存在mRNA表达以及酶活性。在本研究中，我们展示了胚胎和胎儿组织中FAO酶肉碱棕榈酰转移酶1、中链酰基辅酶A脱氢酶和短链羟酰基辅酶A脱氢酶的活性。此外，我们还在胎儿肝脏和肾脏中发现了不同种类的酰基肉碱，这证实了线粒体FAO酶不仅存在于人类胎儿组织中，而且具有代谢活性。在富含葡萄糖的环境中，FAO可能不仅对脂肪酸产生额外的ATP有必要，而且对生长中胎儿膜周转产物脂肪酸的分解也有必要。长链FAO缺陷中早产、宫内生长迟缓、胎儿发病率和宫内死亡的发生率较高，这一事实进一步强调了FAO在人类胚胎和胎儿中的重要性。此外，在动物研究中，已观察到早期胚胎发育期间由于FAO紊乱导致的妊娠丢失。最后，有迹象表明，胎儿发育过程中FAO活性的调节不仅对胎儿生命很重要，而且可能对成年后的健康和疾病也有影响。
