Ornithine decarboxylase (ODC)

Ornithine decarboxylase (ODC) is a PLP-dependent decarboxylase, belongs to the Orn/Lys/Arg decarboxylase class II family (which also includes arginine decarboxylase and lysine decarboxylase). ODC catalyzes the rate-limiting step in the biosynthesis of polyamines (the decarboxylation of the urea cycle intermediate l-ornithine to give putrescine). ODC exists in prokaryotes and eukaryotes, with different folding types (fold-type I and fold-type II, respectively). That is, when ODC is activated, it forms dimers, which can further be used as small units, oligomerized into hexamers, or even dodecamers. Since polyamines are closely related to cell functions such as cell growth and proliferation, DNA stability, gene transcription and translation, and ion channel activity, ODC is a key target for the preparation of drugs to combat proliferative diseases. For example, in highly proliferative tumor cells, polyamine levels are significantly increased, and inhibiting ODC may inhibit cancer development. Excessive accumulation of polyamines can also have cytotoxic effects on cells. In order to maintain normal cell proliferation, the anti-enzyme (ODC) AZ1 negatively regulates polyamine synthesis. AZ binds to ODC to form an ODC-antizyme heterodimer, triggering the 26S proteasome to target the heterodimer for degradation. In the presence of polyamines, AZ+1 slippage occurs, which in turn reduces the abundance of ODC, leading to a decrease in polyamine levels, thus completing an autoregulatory feedback loop between AZ and polyamine levels^[1][2][3].

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