URINARY-EXCRETION OF L-CARNITINE AND ACYLCARNITINES BY PATIENTS WITH DISORDERS OF ORGANIC-ACID METABOLISM - EVIDENCE FOR SECONDARY INSUFFICIENCY OF L-CARNITINE
URINARY-EXCRETION OF L-CARNITINE AND ACYLCARNITINES BY PATIENTS WITH DISORDERS OF ORGANIC-ACID METABOLISM - EVIDENCE FOR SECONDARY INSUFFICIENCY OF L-CARNITINE
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DOI：
10.1203/00006450-198412000-00021
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发表时间：
1984-01-01
影响因子：
3.6
通讯作者：
HOPPEL, CL
中科院分区：
文献类型：
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作者：
CHALMERS, RA;ROE, CR;HOPPEL, CL
L-肉毒碱和酰基肉毒碱的浓度进行了测定，从患者的尿液中的有机酸代谢障碍与线粒体内积累的酰基辅酶A中间体。这些包括丙酸血症、甲基丙二酸尿症、异戊酸血症、多羧化酶缺乏症、3-羟基-3-甲基谷氨酸尿症、甲基乙酰乙酰辅酶A硫解酶缺乏症和各种二羧酸尿症，包括谷氨酸尿症、中链酰基辅酶A脱氢酶缺乏症和多重酰基辅酶A脱氢酶缺乏症。在所有情况下，酰基肉毒碱的浓度大大高于正常水平，游离肉毒碱浓度范围从无法检测到超正常值。酰基肉毒碱/肉毒碱的比率升高到2.0 ±-的正常值以上。1.1.左旋肉碱给予这些患者中的3例;在每种情况下，血浆和尿液中的肉毒碱浓度增加，伴随着短链酰基肉毒碱浓度的显着增加。这些酰基肉毒碱已被检查使用快原子轰击质谱在这些疾病中的一些，并已被证明是丙酰肉毒碱在甲基丙二酸尿症和丙酸血症，异戊酰肉毒碱在异戊酸血症，和己酰肉毒碱和辛酰肉毒碱中链酰基辅酶A脱氢酶缺乏症。这些酰基肉毒碱的排泄与这些疾病中相应酰基辅酶A酯的已知积累相容。 在这组疾病中，尿和血浆中酰基肉毒碱/肉毒碱比率增加表明线粒体质量作用稳态失衡，因此酰基辅酶A/辅酶A比率失衡。尽管自然发生的尝试，以增加内源性L-肉碱的生物合成，有足够的肉毒碱可用于恢复的质量作用比所证明的进一步增加酰基肉毒碱排泄时，患者口服L-肉毒碱。因此，左旋肉碱不足是这些疾病的普遍现象。
Concentrations of l-carnitine and acylcarnitines were determined in urine from patients with disorders of organic acid metabolism associated with an intramitochondrial accumulation of acyl-CoA intermediates. These included propionic acidemia, methylmalonic aciduria, isovaleric acidemia, multicarboxylase deficiency, 3-hydroxy-3-methylglutaric aciduria, methylacetoacetyl-CoA thiolase deficiency, and various dicarboxylic acidurias including glutaric aciduria, medium-chain acyl-CoA dehydrogenase deficiency, and multiple acyl-CoA dehydrogenase deficiency. In all cases, concentrations of acylcarnitines were greatly increased above normal with free carnitine concentrations ranging from undetectable to supranormal values. The ratios of acylcarnitine/carnitine were elevated above the normal value of 2.0 .+-. 1.1. l-Carnitine was given to 3 of these patients; in each case, concentrations of plasma and urine carnitines increased accompanied by a marked increase in concentrations of short-chain acylcarnitines. These acylcarnitines have been examined using fast atom bombardment mass spectrometry in some of these diseases and have been shown to be propionylcarnitine in methylmalonic aciduria and propionic acidemia, isovalerylcarnitine in isovaleric acidemia, and hexanoylcarnitine and octanoylcarnitine in medium-chain acyl-CoA dehydrogenase deficiency. The excretion of these acylcarnitines is compatible with the known accumulation of the corresponding acyl-CoA esters in these diseases. In this group of disorders, the increased acylcarnitine/carnitine ratio in urine and plasma indicates an imbalance of mitochondrial mass action homeostasis and, hence, of acyl-CoA/CoA ratios. Despite natrually occurring attempts to increase endogenous l-carnitine biosynthesis, there is insufficient carnitine available to restore the mass action ratio as demonstrated by the further increase in acylcarnitine excretion when patients were given oral l-carnitine. Thus, l-carnitine insufficiency is a general phenomenon in these diseases.