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。
L-carnitine enhances excretion of propionyl coenzyme A as propionylcarnitine in propionic acidemia.
作者信息
Roe C R, Millington D S, Maltby D A, Bohan T P, Hoppel C L
出版信息
J Clin Invest. 1984 Jun;73(6):1785-8. doi: 10.1172/JCI111387.
Abstract
Treatment with L-carnitine greatly enhanced the formation and excretion of short-chain acylcarnitines in three patients with propionic acidemia and in three normal controls. The use of fast atom bombardment mass spectrometry and linked scanning at constant magnetic (B) to electric (E) field ratio identified the acylcarnitine as propionylcarnitine in patients with propionic acidemia. The normal children excreted mostly acetylcarnitine. Propionic acidemia and other organic acidurias are characterized by the intramitochondrial accumulation of short-chain acyl-Coenzyme A (CoA) compounds. The substrate specificity of the carnitine acetyltransferase enzyme and its steady state nature appears to facilitate elimination of propionyl groups while restoring the acyl-CoA:free CoA ratio in the mitochondrion. We suggest that L-carnitine may be a useful therapeutic approach for elimination of toxic acyl CoA compounds in several of these disorders.
摘要
左旋肉碱治疗显著增强了三名丙酸血症患者和三名正常对照者体内短链酰基肉碱的生成和排泄。使用快原子轰击质谱法以及在恒定磁场（B）与电场（E）比值下的联动扫描，确定丙酸血症患者体内的酰基肉碱为丙酰肉碱。正常儿童主要排泄乙酰肉碱。丙酸血症和其他有机酸尿症的特征是线粒体中短链酰基辅酶A（CoA）化合物的蓄积。肉碱乙酰转移酶的底物特异性及其稳态性质似乎有助于消除丙酰基团，同时恢复线粒体中酰基辅酶A与游离辅酶A的比例。我们认为左旋肉碱可能是消除这些疾病中几种有毒酰基辅酶A化合物的一种有用的治疗方法。
相似文献
1
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.
2
Urinary excretion of l-carnitine and acylcarnitines by patients with disorders of organic acid metabolism: evidence for secondary insufficiency of l-carnitine.有机酸代谢紊乱患者尿中左旋肉碱和酰基肉碱的排泄：左旋肉碱继发性缺乏的证据
Pediatr Res. 1984 Dec;18(12):1325-8. doi: 10.1203/00006450-198412000-00021.
3
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.
4
Identification of undescribed medium-chain acylcarnitines present in urine of patients with propionic and methylmalonic acidemias.鉴定丙酸血症和甲基丙二酸血症患者尿液中存在的未描述的中链酰基肉碱。
Clin Chim Acta. 2000 May;295(1-2):87-96. doi: 10.1016/s0009-8981(00)00195-9.
5
Propionylcarnitine excretion in propionic and methylmalonic acidurias: a cause of carnitine deficiency.丙酸血症和甲基丙二酸血症中丙酰肉碱的排泄：肉碱缺乏的一个原因。
Clin Chim Acta. 1984 May 16;139(1):13-21. doi: 10.1016/0009-8981(84)90187-6.
6
Carnitine therapy and metabolism in the disorders of propionyl-CoA metabolism studied using 1H-NMR spectroscopy.使用核磁共振光谱研究丙酰辅酶A代谢紊乱中的肉碱疗法与代谢。
Clin Chim Acta. 1991 Dec 31;204(1-3):263-77. doi: 10.1016/0009-8981(91)90237-7.
7
Carnitine deficiency in inherited organic acid disorders and Reye syndrome.遗传性有机酸血症和瑞氏综合征中的肉碱缺乏症
Acta Paediatr Jpn. 1990 Aug;32(4):410-6. doi: 10.1111/j.1442-200x.1990.tb00854.x.
8
Metabolic studies of carnitine in a child with propionic acidemia.一名丙酸血症患儿肉碱的代谢研究。
Pediatr Res. 1989 Jul;26(1):63-6. doi: 10.1203/00006450-198907000-00018.
9
Renal handling of carnitine in secondary carnitine deficiency disorders.继发性肉碱缺乏症中肾脏对肉碱的处理
Pediatr Res. 1993 Jul;34(1):89-97. doi: 10.1203/00006450-199307000-00021.
10
Carnitine metabolism in the vitamin B-12-deficient rat.维生素B12缺乏大鼠的肉碱代谢
Biochem J. 1988 Oct 1;255(1):153-9. doi: 10.1042/bj2550153.
引用本文的文献
1
How mass spectrometry revolutionized newborn screening.质谱技术如何彻底改变新生儿筛查。
J Mass Spectrom Adv Clin Lab. 2024 Jan 30;32:1-10. doi: 10.1016/j.jmsacl.2024.01.006. eCollection 2024 Apr.
2
Pathophysiological mechanisms of complications associated with propionic acidemia.丙酸血症相关并发症的病理生理机制。
Pharmacol Ther. 2023 Sep;249:108501. doi: 10.1016/j.pharmthera.2023.108501. Epub 2023 Jul 22.
3
Organic Aciduria Disorders in Pregnancy: An Overview of Metabolic Considerations.妊娠期有机酸尿症：代谢方面的概述
Metabolites. 2023 Apr 4;13(4):518. doi: 10.3390/metabo13040518.
4
Long-term effectiveness of carglumic acid in patients with propionic acidemia (PA) and methylmalonic acidemia (MMA): a randomized clinical trial.瓜氨酸血症、丙酸血症和甲基丙二酸血症患者长期使用卡谷氨酸治疗的疗效：一项随机临床试验。
Orphanet J Rare Dis. 2021 Oct 11;16(1):422. doi: 10.1186/s13023-021-02032-8.
5
Propionate and Alzheimer's Disease.丙酸盐与阿尔茨海默病
Front Aging Neurosci. 2021 Jan 11;12:580001. doi: 10.3389/fnagi.2020.580001. eCollection 2020.
6
Increased protein propionylation contributes to mitochondrial dysfunction in liver cells and fibroblasts, but not in myotubes.蛋白质丙酰化增加导致肝细胞和成纤维细胞中线粒体功能障碍，但不会导致肌管中线粒体功能障碍。
J Inherit Metab Dis. 2021 Mar;44(2):438-449. doi: 10.1002/jimd.12296. Epub 2020 Aug 17.
7
Propionate-induced changes in cardiac metabolism, notably CoA trapping, are not altered by l-carnitine.丙酸盐引起的心脏代谢变化，特别是 CoA 捕获，不受左旋肉碱的影响。
Am J Physiol Endocrinol Metab. 2018 Oct 1;315(4):E622-E633. doi: 10.1152/ajpendo.00081.2018. Epub 2018 Jul 17.
8
The Impact of Carnitine on Dietary Fiber and Gut Bacteria Metabolism and Their Mutual Interaction in Monogastrics.肉碱对单胃动物膳食纤维和肠道细菌代谢的影响及其相互作用。
Int J Mol Sci. 2018 Mar 28;19(4):1008. doi: 10.3390/ijms19041008.
9
Disorders of branched chain amino acid metabolism.支链氨基酸代谢紊乱
Transl Sci Rare Dis. 2016 Nov 7;1(2):91-110. doi: 10.3233/TRD-160009.
10
Propionyl-CoA carboxylase - A review.丙酰辅酶 A 羧化酶 - 综述。
Mol Genet Metab. 2017 Dec;122(4):145-152. doi: 10.1016/j.ymgme.2017.10.002. Epub 2017 Oct 7.
本文引用的文献
1
Relationship between acid-soluble carnitine and coenzyme A pools in vivo.体内酸溶性肉碱与辅酶A库之间的关系。
Biochem J. 1980 Sep 15;190(3):495-504. doi: 10.1042/bj1900495.
2
The specific inhibition of the pyruvate dehydrogenase complex from pig kidney by propionyl-CoA and isovaleryl-Co-A.丙酰辅酶A和异戊酰辅酶A对猪肾丙酮酸脱氢酶复合体的特异性抑制作用。
Biochem Med. 1981 Aug;26(1):20-7. doi: 10.1016/0006-2944(81)90026-0.
3
C6-C10-dicarboxylic aciduria: investigations of a patient with riboflavin responsive multiple acyl-CoA dehydrogenation defects.C6 - C10 - 二羧酸尿症：一名对核黄素反应性多种酰基辅酶A脱氢酶缺陷患者的研究
Pediatr Res. 1982 Oct;16(10):861-8. doi: 10.1203/00006450-198210000-00012.
4
Glycine cleavage system in ketotic hyperglycinemia: a reduction of H-protein activity.酮症性高甘氨酸血症中的甘氨酸裂解系统：H蛋白活性降低。
Pediatr Res. 1982 Jan;16(1):5-7. doi: 10.1203/00006450-198201001-00002.
5
Propionate inhibition of succinate:CoA ligase (GDP) and the citric acid cycle in mitochondria.丙酸盐对线粒体中琥珀酸：辅酶A连接酶（GDP）和柠檬酸循环的抑制作用。
Pediatr Res. 1980 Oct;14(10):1127-31. doi: 10.1203/00006450-198010000-00008.
6
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.
7
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.
8
Carnitine metabolism and deficiency syndromes.肉碱代谢与缺乏综合征
Mayo Clin Proc. 1983 Aug;58(8):533-40.
9
Hypocarnitinemia in disorders of organic acid metabolism.有机酸代谢紊乱中的低肉碱血症。
Lancet. 1982 Aug 28;2(8296):500-1. doi: 10.1016/s0140-6736(82)90532-3.
10
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.
Zotero 插件