Van Hove J L, Kahler S G, Millington D S, Roe D S, Chace D H, Heales S J, Roe C R
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710.
Pediatr Res. 1994 Jan;35(1):96-101. doi: 10.1203/00006450-199401000-00020.
The purpose of this study was to determine whether treatment with L-carnitine or acetyl-L-carnitine enhances the turnover of lipid or branched-chain amino acid oxidation in patients with inborn errors of metabolism. Increasing i.v. doses of L-carnitine and acetyl-L-carnitine were given to one patient with medium-chain acyl-CoA dehydrogenase deficiency and to another with isovaleric acidemia. Both patients were in stable condition and receiving oral L-carnitine supplements. The excretion of carnitine and disease-specific metabolites was measured. The incorporation of L-carnitine in the intracellular pool was demonstrated using stable isotopes and mass spectrometry. Increasing doses of either i.v. L-carnitine or acetyl-L-carnitine did not stimulate the excretion of octanoylcarnitine in the patient with medium-chain acyl-CoA dehydrogenase deficiency, nor did it raise the plasma levels of either cis-4-decenoate or octanoylcarnitine. Similarly, increasing doses of either i.v. L-carnitine or acetyl-L-carnitine did not enhance the excretion of isovalerylcarnitine in a patient with isovaleric acidemia. The excretion of isovalerylglycine actually decreased. We conclude that there was no evidence of enhanced fatty acid beta-oxidation or enhanced branched-chain amino acid oxidation in vivo by the administration of high doses of L-carnitine or acetyl-L-carnitine in these two patients. Because only one individual with each disorder was studied, the data are only indicative and may not necessarily be representative of all individuals with these disorders. Definite settlement of this issue will require further studies in additional subjects.
本研究的目的是确定用左旋肉碱或乙酰左旋肉碱治疗是否能提高先天性代谢缺陷患者的脂质周转率或支链氨基酸氧化率。给一名中链酰基辅酶A脱氢酶缺乏症患者和另一名异戊酸血症患者静脉注射递增剂量的左旋肉碱和乙酰左旋肉碱。两名患者病情均稳定，且正在接受口服左旋肉碱补充剂治疗。测定了肉碱和疾病特异性代谢产物的排泄情况。使用稳定同位素和质谱法证实了左旋肉碱在细胞内池中的掺入。递增剂量的静脉注射左旋肉碱或乙酰左旋肉碱均未刺激中链酰基辅酶A脱氢酶缺乏症患者辛酰肉碱的排泄，也未提高顺式-4-癸烯酸或辛酰肉碱的血浆水平。同样，递增剂量的静脉注射左旋肉碱或乙酰左旋肉碱均未增强异戊酸血症患者异戊酰肉碱的排泄。异戊酰甘氨酸的排泄实际上减少了。我们得出结论，在这两名患者中，没有证据表明高剂量的左旋肉碱或乙酰左旋肉碱能在体内增强脂肪酸β氧化或增强支链氨基酸氧化。由于每种疾病仅研究了一名个体，这些数据仅具有指示性，不一定代表所有患有这些疾病的个体。要明确解决这个问题，还需要对更多受试者进行进一步研究。
