TRANSPORT AND METABOLISM OF SARCOSINE IN HYPERSARCOSINEMIC AND NORMAL PHENOTYPES
TRANSPORT AND METABOLISM OF SARCOSINE IN HYPERSARCOSINEMIC AND NORMAL PHENOTYPES
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DOI：
10.1172/jci106729
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发表时间：
1971-01-01
影响因子：
15.9
通讯作者：
MOHYUDDIN, F
中科院分区：
文献类型：
--
作者：
GLORIEUX, FH;SCRIVER, CR;MOHYUDDIN, F
在一个法裔加拿大家庭中偶然发现了一名患有高海氨酸血症的青春期男性先证者；没有特定的疾病与这一特征有关。即使在药理剂量(30毫克/天)的情况下，饮食中的叶酸也不能减少高海氨酸血症。在培养的人皮肤成纤维细胞和白细胞中证实了肌氨酸脱氢酶的正常缺失，从而消除了这些组织作为进一步研究突变的肌氨酸血症表型和基因类型的有用来源。肌氨酸负荷后，血浆中肌氨酸和甘氨酸的反应，区分了正常受试者和推测为高砷血症等位基因纯合子和杂合子的受试者。在推测的纯合子中，肌氨酸从血浆中清除的时间大大延迟(tç，6.1小时)，在推测的杂合子中略有延迟(t？，2.2小时)，而甘氨酸在前者中保持不变，在后者中升高。正常受试者迅速从血浆中清除肌氨酸(tç，1.6小时)，而血浆甘氨酸呈下降趋势。表型反应提示，高精氨酸血症是该家系的常染色体隐性遗传特征。先证者肾小管肌氨酸转运正常，尽管他可能缺乏正常发生在肾脏的肌氨酸氧化。因此，肌氨酸的分解代谢对其自身的肾脏吸收并不重要。肌氨酸在体内的吸收过程中与脯氨酸和甘氨酸相互作用。在大鼠肾脏的体外研究表明，肌氨酸转运是中介的、可饱和的和能量依赖的。肌氨酸本身没有明显的转运系统；它利用L-脯氨酸和甘氨酸的低Km转运系统，以及这些物质共享的高Km转运系统，主要摄取高抗坏血素血症时遇到的浓度。细胞内高浓度的肌氨酸将在其中一个系统上与甘氨酸交换，这可能解释了肌氨酸负荷后甘氨酸肾脏转运的矛盾改善。
An adolescent male proband with hypersarcosinemia was discovered incidentally in a French-Canadian family; no specific disease was associated with the trait. The hypersarcosinemia is not diminished by dietary folic acid even in pharmacologic doses (30 mg/day). The normal absence of sarcosine dehydrogenase in cultured human skin fibroblasts and in leukocytes was confirmed, thus eliminating these tissues as useful sources for further investigation of mutant sarcosinemic phenotypes and genotypes.The response in plasma of sarcosine and glycine, after sarcosine loading, distinguished the normal subject from the subjects who were presumably homozygous and heterozygous for the hypersarcosinemia allele. Sarcosine clearance from plasma was delayed greatly (t½, 6.1 hr) in the presumed homozygote and slightly (t½, 2.2 hr) in the presumed heterozygote, while plasma glycine remained constant in the former and rose in the latter. Normal subjects clear sarcosine from plasma rapidly (t½, 1.6 hr) while their plasma glycine trend is downward. The phenotypic responses suggest that hypersarcosinemia is an autosomal recessive trait in this pedigree.Renal tubular transport of sarcosine was normal in the proband even though he presumably lacked the sarcosine oxidation which should normally occur in kidney. Sarcosine catabolism is thus not important for its own renal uptake.Sarcosine interacts with proline and glycine during its absorption in vivo. Studies in vitro in rat kidney showed that sarcosine transport is mediated, saturable, and energy dependent. Sarcosine has no apparent transport system of its own; it uses the lowKmtransport systems for L-proline and glycine to a minor extent and a highKmsystem shared by these substances for the major uptake at concentrations encountered in hypersarcosinemia. Intracellular sarcosine at high concentration will exchange with glycine on one of these systems, which may explain a paradoxical improvement in renal transport of glycine after sarcosine loading in the hypersarcosinemic proband.