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恶性细胞中的同型半胱氨酸硫内酯代谢

Homocysteine thiolactone metabolism in malignant cells.

作者信息

McCully K S

出版信息

Cancer Res. 1976 Sep;36(9 pt.1):3198-202.

PMID:975084
Abstract

Since abnormal homocysteine metabolism is associated with several disorders of growth, including neoplasia, the metabolic fate of homocysteine thiolactone was studied in cell cultures from several malignant tumors, established cell lines, cell lines transformed by oncogenic viruses, and normal skin cells. In all of the cultures of malignant cells homocysteine thiolactone becaome incorporated in peptide linkage with cellular proteins (thiolation). Normal cells incorporated homocysteine thiolactone in peptide linkage, but homocysteine thiolactone was released by acid hydrolysis. The findings suggest the speculative possibility that malignant cells are deficient in a homocysteine thiolactone derivative that prevents thiolation of proteins by homocysteine thiolactone. This hypothetical substance may also catalyze the synthesis of methionine and release acrolein, a growth-regulatory substance, in normal cells. The growth characteristics and tumorigenicity of cultured cells may be related to depletion of the hypothetical substance, and its identification, synthesis, and administration to animals would be expected to affect growth of malignant neoplasms.

摘要

由于同型半胱氨酸代谢异常与包括肿瘤形成在内的多种生长紊乱有关,因此在几种恶性肿瘤的细胞培养物、已建立的细胞系、致癌病毒转化的细胞系以及正常皮肤细胞中研究了同型半胱氨酸硫内酯的代谢命运。在所有恶性细胞培养物中,同型半胱氨酸硫内酯都与细胞蛋白质形成肽键结合(硫醇化)。正常细胞将同型半胱氨酸硫内酯结合到肽键中,但同型半胱氨酸硫内酯可通过酸水解释放出来。这些发现提示了一种推测性的可能性,即恶性细胞缺乏一种同型半胱氨酸硫内酯衍生物,该衍生物可防止同型半胱氨酸硫内酯对蛋白质进行硫醇化。这种假设的物质在正常细胞中还可能催化蛋氨酸的合成并释放出一种生长调节物质丙烯醛。培养细胞的生长特性和致瘤性可能与这种假设物质的消耗有关,预期对其进行鉴定、合成并给予动物将影响恶性肿瘤的生长。

相似文献

1
Homocysteine thiolactone metabolism in malignant cells.恶性细胞中的同型半胱氨酸硫内酯代谢
Cancer Res. 1976 Sep;36(9 pt.1):3198-202.
2
Growth disorders and homocysteine metabolism.
Ann Clin Lab Sci. 1975 May-Jun;5(3):147-52.
3
Chemical pathology of homocysteine. II. Carcinogenesis and homocysteine thiolactone metabolism.同型半胱氨酸的化学病理学。II. 致癌作用与同型半胱氨酸硫内酯代谢
Ann Clin Lab Sci. 1994 Jan-Feb;24(1):27-59.
4
Inhibition of neoplastic growth by N-homocysteine thiolactonyl retinamido cobalamin.N-同型半胱氨酸硫内酯基视黄酰胺钴胺素对肿瘤生长的抑制作用。
Res Commun Chem Pathol Pharmacol. 1989 Oct;66(1):117-22.
5
Tumor therapy by deprivation of L-methionine: rationale and results.通过剥夺L-甲硫氨酸进行肿瘤治疗:原理与结果
Cancer Treat Rep. 1979 Jun;63(6):1069-72.
6
Chemical pathology of homocysteine. III. Cellular function and aging.
Ann Clin Lab Sci. 1994 Mar-Apr;24(2):134-52.
7
Methionine requirement and replacement by homocysteine in tissue cultures of selected rodent and human malignant and normal cells.在选定的啮齿动物和人类恶性及正常细胞的组织培养中蛋氨酸需求及同型半胱氨酸对其的替代作用
Cancer Res. 1978 Aug;38(8):2259-62.
8
Homocysteine thiolactone in arteriosclerosis and cancer.
Res Commun Chem Pathol Pharmacol. 1988 Jan;59(1):107-19.
9
Effect of nutritional and enzymatic methionine deprivation upon human normal and malignant cells in tissue culture.营养性和酶促性蛋氨酸剥夺对组织培养中的人正常细胞和恶性细胞的影响。
Cancer Res. 1980 Mar;40(3):634-41.
10
Analysis of cell-cycle kinetics and sulfur amino acid metabolism in methionine-dependent tumor cell lines; the effect of homocysteine supplementation.蛋氨酸依赖型肿瘤细胞系的细胞周期动力学和硫氨基酸代谢分析;补充同型半胱氨酸的影响。
Biochem Pharmacol. 2004 Apr 15;67(8):1587-99. doi: 10.1016/j.bcp.2004.01.006.

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Front Aging Neurosci. 2017 Oct 6;9:324. doi: 10.3389/fnagi.2017.00324. eCollection 2017.