Ascorbate-dependent hydroxylase

Ascorbate-dependent hydroxylases and oxidoreductases are a functionally diverse group of enzymes that require ascorbic acid (vitamin C) as an electron donor, typically to maintain a reduced metal cofactor (such as Fe²⁺ or Cu²⁺) within the enzyme’s active site[2][5][6]. Key families include 2-oxoglutarate-dependent dioxygenases (2-OGDDs), which hydroxylate proline or lysine residues in collagen, regulate hypoxia responses (e.g., HIF prolyl hydroxylases), and mediate epigenetic modifications (e.g., DNA and histone demethylation by TET enzymes)[3][4][6]; and copper type II ascorbate-dependent monooxygenases, like dopamine β-monooxygenase (for catecholamine synthesis)[5]. Ascorbate is essential for these reactions, and deficiency impairs enzyme activity, affecting tissue integrity, gene regulation, and metabolic pathways[2][4]. The grouping “ascorbate-dependent hydroxylases/oxidoreductases” is broad and not a single molecular entity but represents a mechanistic category containing several distinct, clinically relevant enzymes.\n\nNote: \n- The term "ascorbate-dependent hydroxylases/oxidoreductases" is not a canonical molecular entity but describes a class of enzymes sharing this chemical dependence. For specific entries, use precise enzyme names (e.g., "Prolyl 4-hydroxylase," "TET1") for structured databases. This entry is too broad for most therapeutic target databases and should be split into sub-entities where possible.\n- Many but not all of these enzymes are considered therapeutic targets; some have direct inhibitors or modulators in clinical use or development, especially HIF-prolyl hydroxylases and TET demethylases[6].

Other names

Ascorbate-dependent oxidoreductase2-oxoglutarate-dependent dioxygenase (for a major subclass)Copper type II, ascorbate-dependent monooxygenase (for a subclass)Prolyl hydroxylase, lysyl hydroxylase, dopamine β-hydroxylase, ascorbate peroxidase, cytochrome b561 (examples of family members, not general aliases)

Ascorbate donates electrons to maintain enzyme active-site metals in reduced state, enabling hydroxylation or monooxygenation of substrates[2][5][6]\nAscorbate can act as a reducing cofactor for the Fe(II) or Cu(II) center, preventing oxidative inactivation of the enzyme[5][6]\nFor HIF-PHD inhibitors: stabilize HIF by blocking its hydroxylation and thus proteasomal degradation[6]