Canine hereditary ceroid-lipofuscinosis: evidence for a defect in the carnitine biosynthetic pathway.
Canine hereditary ceroid-lipofuscinosis: evidence for a defect in the carnitine biosynthetic pathway.
复制标题
犬遗传性蜡样质脂褐质沉着症：肉碱生物合成途径缺陷的证据。
DOI：
10.1002/ajmg.1320570231
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Siakotos,AN
中科院分区：
文献类型：
--
作者：
Katz,ML;Siakotos,AN
ceroid - lipofuscinosis是一组常染色体隐性遗传性溶酶体贮积病，在人类和其他哺乳动物物种中具有特征。在人类疾病的幼年型犬模型中，储存体的主要成分是线粒体ATP合酶的亚基c蛋白，该蛋白含有ε‐N‐三甲基赖氨酸（TML）残基。TML是肉碱生物合成的前体。为了确定含TML蛋白的积累是否可能是由肉毒碱生物合成途径的缺陷引起的，我们测量了纯合子、杂合子携带者和正常狗的血浆肉毒碱和三甲基赖氨酸水平。与正常动物相比，受影响的狗的平均肉碱水平降低了67%，携带病毒的狗的平均肉碱水平降低了50%。携带者的平均血浆TML水平比对照水平高出近50%，但受影响动物的血浆TML水平下降了约25%。携带者血浆中肉毒碱和TML水平的变化与该疾病涉及肉毒碱生物合成途径缺陷的可能性一致。疾病过程的继发性影响可能解释了受感染动物血浆TML水平明显相互矛盾的下降。©1995 Wiley‐Liss, Inc。
The ceroid‐lipofuscinoses are a group of autosomal‐recessive hereditary lysosomal storage diseases that have been characterized in humans and other mammalian species. In a canine model for the juvenile form of the human disease, a major constituent of the storage bodies is the subunit c protein of mitochondrial ATP synthase that contains an ε‐N‐trimethyllysine (TML) residue. TML is a precursor in carnitine biosynthesis. To determine whether accumulation of the TML‐containing protein could result from a defect in the carnitine biosynthetic pathway, plasma carnitine and trimethyllysine levels were measured in homozygous affected, heterozygous carriers, and in normal dogs. When compared to normal animals, mean carnitine levels were reduced by 67% in affected and 50% in carrier dogs. Mean plasma TML levels were elevated almost 50% above control levels in the carriers, but were decreased by approximately 25% in the affected animals. The changes in plasma carnitine and TML levels in the carriers are consistent with the possibility that the disease involves a defect in the carnitine biosynthetic pathway. Secondary effects of the disease process may account for the apparently contradictory decrease in plasma TML levels in affected animals. © 1995 Wiley‐Liss, Inc.