Canellakis E S, Kyriakidis D A, Rinehart C A, Huang S C, Panagiotidis C, Fong W F
Biosci Rep. 1985 Mar;5(3):189-204. doi: 10.1007/BF01119588.
This review considers the role of antizyme, of amino acids and of protein synthesis in the regulation of polyamine biosynthesis. The ornithine decarboxylase of eukaryotic cells and of Escherichia coli can be non-competitively inhibited by proteins, termed antizymes, which are induced by di- and poly- amines. Some antizymes have been purified to homogeneity and have been shown to be structurally unique to the cell of origin. Yet, the E. coli antizyme and the rat liver antizyme cross react and inhibit each other's biosynthetic decarboxylases. These results indicate that aspects of the control of polyamine biosynthesis have been highly conserved throughout evolution. Evidence for the physiological role of the antizyme in mammalian cells rests upon its identification in normal uninduced cells, upon the inverse relationship that exists between antizyme and ornithine decarboxylase as well as upon the existence of the complex of ornithine decarboxylase and antizyme in vivo. Furthermore, the antizyme has been shown to be highly specific; its Keq for ornithine decarboxylase is 1.4 X 10(11) M-1. In addition, mammalian cells contain an anti-antizyme, a protein that specifically binds to the antizyme of an ornithine decarboxylase-antizyme complex and liberates free ornithine decarboxylase from the complex. In E. coli, in which polyamine biosynthesis is mediated both by ornithine decarboxylase and by arginine decarboxylase, three proteins (one acidic and two basic) have been purified, each of which inhibits both these enzymes. They do not inhibit the biodegradative ornithine and arginine decarboxylases nor lysine decarboxylase. The two basic inhibitors have been shown to correspond to the ribosomal proteins S20/L26 and L34, respectively. The relationship of the acidic antizyme to other known E. coli proteins remains to be determined. In mammalian cells, ornithine decarboxylase can be induced by a broad spectrum of compounds. These range from hormones and growth factors to natural amino acids such as asparagine and to non-metabolizable amino acid analogues such as alpha-amino-isobutyric acid. The amino acids that induce ornithine decarboxylase as well as those that promote polyamine uptake utilize the sodium dependent A and N transport systems. Consequently, they act in concert and increase intracellular polyamine levels by both mechanisms. The induction of ornithine decarboxylase by growth factors, such as NGF, EGF, and PDGF as well as by insulin requires the presence of these same amino acids and does not occur in their absence. However, the inducing amino acid need not be incorporated into protein nor covalently modified.(ABSTRACT TRUNCATED AT 400 WORDS)
本综述探讨了抗酶、氨基酸和蛋白质合成在多胺生物合成调控中的作用。真核细胞和大肠杆菌的鸟氨酸脱羧酶可被称为抗酶的蛋白质非竞争性抑制，这些抗酶由二胺和多胺诱导产生。一些抗酶已被纯化至同质，并显示出其在来源细胞中结构独特。然而，大肠杆菌抗酶和大鼠肝脏抗酶可交叉反应并抑制彼此的生物合成脱羧酶。这些结果表明，多胺生物合成的调控在整个进化过程中高度保守。抗酶在哺乳动物细胞中的生理作用证据基于其在正常未诱导细胞中的鉴定、抗酶与鸟氨酸脱羧酶之间存在的反向关系以及体内鸟氨酸脱羧酶与抗酶复合物的存在。此外，抗酶已被证明具有高度特异性；其对鸟氨酸脱羧酶的平衡常数为1.4×10¹¹ M⁻¹。此外，哺乳动物细胞含有一种抗抗酶，一种能特异性结合鸟氨酸脱羧酶 - 抗酶复合物中的抗酶并从复合物中释放游离鸟氨酸脱羧酶的蛋白质。在大肠杆菌中，多胺生物合成由鸟氨酸脱羧酶和精氨酸脱羧酶介导，已纯化出三种蛋白质（一种酸性和两种碱性），每种都能抑制这两种酶。它们不抑制鸟氨酸和精氨酸的生物降解性脱羧酶以及赖氨酸脱羧酶。已证明这两种碱性抑制剂分别对应核糖体蛋白S20/L26和L34。酸性抗酶与其他已知大肠杆菌蛋白质的关系尚待确定。在哺乳动物细胞中，鸟氨酸脱羧酶可被多种化合物诱导。这些化合物从激素和生长因子到天然氨基酸如天冬酰胺，再到不可代谢的氨基酸类似物如α - 氨基异丁酸。诱导鸟氨酸脱羧酶的氨基酸以及促进多胺摄取的氨基酸利用钠依赖性A和N转运系统。因此，它们协同作用，通过这两种机制增加细胞内多胺水平。生长因子如神经生长因子（NGF）、表皮生长因子（EGF）和血小板衍生生长因子（PDGF）以及胰岛素对鸟氨酸脱羧酶的诱导需要这些相同氨基酸的存在，在其不存在时则不会发生。然而，诱导性氨基酸无需掺入蛋白质或进行共价修饰。（摘要截于400字）
