LABILE METHYL-GROUP BALANCES IN THE HUMAN - THE ROLE OF SARCOSINE
LABILE METHYL-GROUP BALANCES IN THE HUMAN - THE ROLE OF SARCOSINE
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DOI：
10.1016/0026-0495(80)90192-4
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发表时间：
1980-01-01
影响因子：
9.8
通讯作者：
SCRIVER, CR
中科院分区：
文献类型：
--
作者：
MUDD, SH;EBERT, MH;SCRIVER, CR
以前发表的对成年人每日蛋氨酸利用率的估计被低估了，因为现有数据不允许对蛋氨酸甲基部分被氧化的速率进行定量评估。据报道，通过中间n -甲基甘氨酸（肌氨酸）的两种途径来测量蛋氨酸甲基氧化的速率。研究了两例肌氨酸血症和肌氨酸尿酸患者，他们被证实或推测在肌氨酸氧化系统中有特定的遗传缺陷，同时维持含有不同量的蛋氨酸、胆碱（或胆碱衍生物）和甘氨酸的恒定饮食。测定肌氨酸、肌酐、肌酸等物质的稳态排泄量。肌氨酸的形成可能有两种方式：一种是与饲粮中摄入的胆碱（或胆碱衍生物）相当的量，由于一个甲基从甜菜碱转移到同型半胱氨酸，这一途径将对蛋氨酸-甲基库产生净正贡献；另一种是需要蛋氨酸甲基的净消耗。对于获得合理完整数据的单个患者，可能会发生2个这样的过程。一个人的速度是（.apprx）。2 mmol/24 h)，随不稳定甲基总摄入量的改变变化不大。当不稳定甲基的摄入量超过合成肌酸（10.2 mmol/24 h）、其他转甲基化反应（1.4 mmol/24 h）、多胺合成（0.5 mmol/24 h）和前面提到的肌氨酸形成的基本过程（2 mmol/24 h）所需的总量时，第2个甲基的摄入量就变得突出（并占了不稳定甲基增量摄入量的大部分）。这种基础肌氨酸的形成可能主要是由于内源性胆碱合成，通过降解来平衡，而肌氨酸形成的更敏感的过程可能主要是由于甘氨酸的甲基化。结合现有数据，这些关于肌氨酸形成引起的蛋氨酸消耗的新数据允许计算s -腺苷蛋氨酸在人肝脏中的周转时间（不超过3.5-7分钟），以及对先前甲基新生率的最小估计进行向上修正。在甲硫氨酸和同型半胱氨酸通过体内的过程中，同型半胱氨酸部分在甲硫氨酸和同型半胱氨酸之间循环的平均时间，以及同型半胱氨酸在再甲基化和转硫化途径之间的分配。
Estimates of the daily rate of methionine utilization by adult humans, published previously, were underestimated because available data did not permit quantitative assessment of the rate at which the methyl moiety of methionine is oxidized. Efforts are reported to measure the rate of oxidation of methionine methyl by the 2 pathways that proceed through the intermediate N-methylglycine (sarcosine). Two sarcosinemic, sarcosinuric patients, proven or presumed to have specific genetic defects in the sarcosine-oxidizing system, were studied while maintained on constant diets containing differing amounts of methionine, choline (or choline derivatives) and glycine. The steady-state excretions of sarcosine, creatinine, creatine and other materials were determined. Sarcosine is probably formed in 2 ways: in an amount equivalent to the dietary intake of choline (or choline derivative), this pathway would make a net positive contribution to the methionine-methyl pool due to the transfer of a methyl group from betaine to homocysteine and by processes requiring net consumption of methionine methyl. For the single patient for whom reasonably complete data were attained, 2 such processes may be occurring. One proceeds at the rate (.apprx. 2 mmol/24 h) that changed little as total intake of labile methyl groups was altered. The 2nd became prominent (and accounted for the bulk of the incremental intake of labile methyl groups) when this intake exceeded the combined amounts required for the synthesis of creatine (10.2 mmol/24 h), other transmethylation reactions (1.4 mmole/24 h), polyamine synthesis (0.5 mmole/24 h) and the basal process of sarcosine formation just mentioned (2 mmole/24 h). Such basal sarcosine formation may be due to chiefly to endogenous choline synthesis, balanced by degradation, whereas the more responsive process of sarcosine formation may be due chiefly to methylation of glycine. Together with available data, these new data on methionine consumption due to sarcosine formation permit calculation of a turnover time for S-adenosylmethionine in human liver (no more than 3.5-7 min), as well as upward revision of previous minimal estimates of the rate of methylneogenesis, the number of time that the average homocysteinyl moiety cycles between methionine and homocysteine during its passage through the body and the partitioning of homocysteine between the remethylation and the transsulfuration pathways.