1 · Normoxia · PHD tags HIF-α
When oxygen is present, PHD uses O₂ to add hydroxyl groups to two prolines on HIF-α, giving it a death tag so it is cleared fast.What every cell does every second: continuously synthesize HIF-α protein, and continuously destroy it.The key: destruction requires oxygen
· PHD (prolyl hydroxylase) — a family of iron + α-ketoglutarate-dependent hydroxylases.
· Uses O₂ as a substrate — this is the chemical essence of "oxygen sensing" (oxygen itself is the switch).
· Adds -OH to two specific prolines on HIF-α (Pro402, Pro564).
Once hydroxylated, HIF-α carries a "death tag" — half-life < 5 minutes. In most conditions we can't detect HIF-α protein because it is being cleared as fast as it's made.