L-肉碱治疗异戊酸血症
L-carnitine therapy in isovaleric acidemia.
作者信息
Roe C R, Millington D S, Maltby D A, Kahler S G, Bohan T P
出版信息
J Clin Invest. 1984 Dec;74(6):2290-5. doi: 10.1172/JCI111657.
Abstract
Isovaleric acidemia, resulting from isovaleryl-coenzyme A dehydrogenase deficiency, is associated with marked reduction of free carnitine in both plasma and urine. Fast atom bombardment-mass spectrometry, hydrolysis, and gas chromatography/mass spectrometry have unequivocally identified the existence of isovalerylcarnitine, a new metabolite specific for this disorder. Administration of equimolar amounts of glycine or L-carnitine separately with leucine demonstrated that isovaleryl-coenzyme A is removed by supplemental L-carnitine in the form of isovalerylcarnitine as effectively as it is by glycine, in the form of isovalerylglycine. When L-carnitine is given alone, excretion of isovalerylglycine decreases in preference to enhanced excretion of isovalerylcarnitine and hippurate. Treatment with L-carnitine alone has proven effective in preventing further hospitalizations in a patient with this genetic disorder.
摘要
异戊酸血症是由异戊酰辅酶A脱氢酶缺乏引起的，与血浆和尿液中游离肉碱的显著减少有关。快速原子轰击质谱法、水解法和气相色谱/质谱法已明确鉴定出异戊酰肉碱的存在，这是一种针对该疾病的新代谢产物。分别将等摩尔量的甘氨酸或L-肉碱与亮氨酸一起给药表明，补充的L-肉碱以异戊酰肉碱的形式去除异戊酰辅酶A的效果与甘氨酸以异戊酰甘氨酸的形式去除异戊酰辅酶A的效果一样有效。单独给予L-肉碱时，异戊酰甘氨酸的排泄减少，而异戊酰肉碱和马尿酸盐的排泄增加不明显。事实证明，单独用L-肉碱治疗可有效防止患有这种遗传性疾病的患者再次住院。
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本文引用的文献
1
Short-chain acylcarnitines of human blood and urine.人体血液和尿液中的短链酰基肉碱
Biochem Med. 1982 Oct;28(2):197-203. doi: 10.1016/0006-2944(82)90070-9.
2
Application of high resolution fast atom bombardment and constant B/E ratio linked scanning to the identification and analysis of acylcarnitines in metabolic disease.高分辨率快原子轰击和恒定B/E比联动扫描在代谢疾病中酰基肉碱鉴定与分析中的应用
Biomed Mass Spectrom. 1984 May;11(5):236-41. doi: 10.1002/bms.1200110508.
3
L-carnitine enhances excretion of propionyl coenzyme A as propionylcarnitine in propionic acidemia.左旋肉碱可促进丙酸血症患者体内丙酰辅酶A以丙酰肉碱形式排出。
J Clin Invest. 1984 Jun;73(6):1785-8. doi: 10.1172/JCI111387.
4
Metabolic response to carnitine in methylmalonic aciduria. An effective strategy for elimination of propionyl groups.甲基丙二酸尿症中肉碱的代谢反应。消除丙酰基的有效策略。
Arch Dis Child. 1983 Nov;58(11):916-20. doi: 10.1136/adc.58.11.916.
5
L-carnitine therapy in propionicacidaemia.左旋肉碱治疗丙酸血症。
Lancet. 1982 Jun 19;1(8286):1411-2. doi: 10.1016/s0140-6736(82)92524-7.
6
The isolation and identification of N-isovalerylglycine from urine of patients with isovaleric acidemia.从异戊酸血症患者尿液中分离和鉴定N-异戊酰甘氨酸。
J Biol Chem. 1967 Jun 25;242(12):2966-72.
7
Propionylcarnitine. Physiological variations in vivo.丙酰肉碱。体内的生理变化。
Biochim Biophys Acta. 1968 May 1;152(3):559-67. doi: 10.1016/0005-2760(68)90096-9.
8
Isovaleric acidemia: a new genetic defect of leucine metabolism.异戊酸血症：一种新的亮氨酸代谢遗传缺陷。
Proc Natl Acad Sci U S A. 1966 Jul;56(1):236-42. doi: 10.1073/pnas.56.1.236.
9
The specificity of glycine-N-acylase and acylglycine excretion in the organicacidaemias.甘氨酸 - N - 酰基转移酶的特异性及有机酸酸血症中酰基甘氨酸的排泄情况。
Biochem Med. 1974 May;10(1):15-23. doi: 10.1016/0006-2944(74)90004-0.
10
Isovaleric acidemia. Clinical features of a new genetic defect of leucine metabolism.异戊酸血症。一种新的亮氨酸代谢遗传缺陷的临床特征。
N Engl J Med. 1967 Aug 17;277(7):321-7. doi: 10.1056/NEJM196708172770701.
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