HEPATIC SYNTHESIS OF CARNITINE FROM PROTEIN-BOUND TRIMETHYL-LYSINE - LYSOSOMAL DIGESTION OF METHYL-LYSINE-LABELED ASIALO-FETUIN
HEPATIC SYNTHESIS OF CARNITINE FROM PROTEIN-BOUND TRIMETHYL-LYSINE - LYSOSOMAL DIGESTION OF METHYL-LYSINE-LABELED ASIALO-FETUIN
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DOI：
10.1042/bj1600085
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发表时间：
1976-01-01
影响因子：
4.1
通讯作者：
ARONSON, NN
中科院分区：
文献类型：
--
作者：
LABADIE, J;DUNN, WA;ARONSON, NN
通过追踪去唾液酸胎球蛋白的两种放射性衍生物的代谢，研究了大鼠体内肉毒碱的生物合成。第一个包含 14C 标记的甲基，与其赖氨酸残基的 6-N-氨基部分共价结合，作为 6-N-单甲基-和二甲基-赖氨酸。通过用碘甲烷处理该蛋白质，产生了第二衍生物，其中放射性优先以6-N-[甲基-14C]-三甲基-赖氨酸的形式掺入。这些去唾液酸化的糖蛋白，像其他脱唾液酸蛋白一样，立即被大鼠肝脏从血液中清除。在肝细胞溶酶体中，14C 标记的蛋白质迅速水解，产生含有各种 6-N-[甲基-14C]甲基化赖氨酸残基的游离氨基酸。放射性氨基酸穿过溶酶体膜并在细胞质中进一步代谢。肉碱是在静脉注射后大鼠尸体和肝脏提取物中检测到的主要放射性代谢物。注射6-N-[甲基-14C]三甲基赖氨酸标记的脱唾液酸胎球蛋白。 3小时内，所施用蛋白质中至少34.6%的三甲基赖氨酸转化为肉碱。分离的灌注大鼠肝脏在 90 分钟内将 30% 的添加肽结合三甲基赖氨酸转化为肉碱。注射 6-N-[甲基-14C]-单甲基-和-二甲基-赖氨酸标记的去唾液酸胎球蛋白后 20 分钟至 22 小时，放射性肉碱在大鼠肝脏和尸体中反复缺失。这些数据为肉毒碱生物合成途径提供了证据，该途径涉及三甲基赖氨酸作为肽结合前体，如 R.A.考克斯和 C. L. 霍佩尔。研究结果还表明，大鼠肝脏可以在没有其他组织帮助的情况下合成肉碱，但不能将游离的部分甲基化赖氨酸转化为三甲基赖氨酸。
The biosynthesis of carnitine in the rat was studied by following the metabolism of 2 radioactive derivatives of asialo-fetuin. The 1st contained 14C-labeled methyl groups covalently bound to the 6-N-amino fraction of its lysine residues as 6-N-monomethyl- and dimethyl-lysine. By treating this protein with iodomethane, a 2nd derivative was produced in which the radioactivity was preferentially incorporated as 6-N-[methyl-14C]-trimethyl-lysine. These desialylated glycoproteins, like other asialo-proteins, were immediately cleared from the blood by rat liver. Within hepatocyte lysosomes, the 14C-labeled proteins were rapidly hydrolysed, producing free amino acids containing the various 6-N-[methyl-14C]methylated lysine residues. The radioactive amino acids crossed the lysosomal membrane and were further metabolized in the cytosol. Carnitine was the major radioactive metabolite detected in extracts of rat carcass and liver after i.v. injection of 6-N-[methyl-14C]trimethyl-lysine-labeled asialo-fetuin. Within 3 h, at least 34.6% of the trimethyl-lysine in the administered protein was converted into carnitine. An isolated perfused rat liver converted 30% of the added peptide-bound trimethyl-lysine into carnitine within 90 min. Radioactive carnitine was repeatedly absent from both rat liver and carcass between 20 min and 22 h after injection of 6-N-[methyl-14C]-monomethyl- and -dimethyl-lysine-labeled asialofetuin. These data provide evidence for a pathway of carnitine biosynthesis that involves trimethyl-lysine as a peptide-bound precursor as proposed by R.A. Cox and C. L. Hoppel. The findings also show that rat liver can synthesize carnitine without the aid of other tissues, but cannot convert free partially methylated lysines into trimethyl-lysine.