Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
Essays Biochem. 2009 Nov 4;46:47-61. doi: 10.1042/bse0460004.
Polyamines are small aliphatic polycations present in all living cells. Polyamines are essential for cellular viability and are involved in regulating fundamental cellular processes, most notably cellular growth and proliferation. Being such central regulators of fundamental cellular functions, the intracellular polyamine concentration is tightly regulated at the levels of synthesis, uptake, excretion and catabolism. ODC (ornithine decarboxylase) is the first key enzyme in the polyamine biosynthesis pathway. ODC is characterized by an extremely rapid intracellular turnover rate, a trait that is central to the regulation of cellular polyamine homoeostasis. The degradation rate of ODC is regulated by its end-products, the polyamines, via a unique autoregulatory circuit. At the centre of this circuit is a small protein called Az (antizyme), whose synthesis is stimulated by polyamines. Az inactivates ODC and targets it to ubiquitin-independent degradation by the 26S proteasome. In addition, Az inhibits uptake of polyamines. Az itself is regulated by another ODC-related protein termed AzI (antizyme inhibitor). AzI is highly homologous with ODC, but it lacks ornithine-decarboxylating activity. Its ability to serve as a regulator is based on its high affinity to Az, which is greater than the affinity Az has to ODC. As a result, it interferes with the binding of Az to ODC, thus rescuing ODC from degradation and permitting uptake of polyamines.
多胺是存在于所有活细胞中的小脂族聚阳离子。多胺对细胞活力至关重要，参与调节基本的细胞过程，特别是细胞生长和增殖。作为基本细胞功能的核心调节剂，细胞内多胺浓度在合成、摄取、排泄和分解代谢水平上受到严格调节。ODC（鸟氨酸脱羧酶）是多胺生物合成途径中的第一个关键酶。ODC 的特点是细胞内周转率极高，这是调节细胞多胺动态平衡的核心特征。ODC 的降解速率受其终产物多胺通过独特的自动调节回路调节。该回路的核心是一种称为 Az（抗酶）的小蛋白，其合成受多胺刺激。Az 使 ODC 失活，并将其靶向到 26S 蛋白酶体进行非依赖泛素的降解。此外，Az 抑制多胺的摄取。Az 本身受另一种称为 AzI（抗酶抑制剂）的 ODC 相关蛋白调节。AzI 与 ODC 高度同源，但缺乏鸟氨酸脱羧酶活性。它作为调节剂的能力基于其对 Az 的高亲和力，该亲和力大于 Az 与 ODC 的亲和力。结果，它干扰了 Az 与 ODC 的结合，从而使 ODC 免于降解，并允许多胺摄取。
