Fig. 5.

Proposed regulatory model of DDC levels in the brain: Only Pyridoxal (PL), Pyridoxine (PN), or Pyridoxamine (PM) can cross the blood brain barrier, mostly at the choroid plexi. PLP is first cleaved to pyridoxal by nonspecific membrane-associated alkaline phosphatases. Once in the brain cell, B₆ vitamers are converted again in PLP by PL kinase, and directly or indirectly transferred to apoenzymes. PLP transfer may be facilitated by the open conformation of the apoenzyme presented in the present paper. The active holo- form is responsible for the synthesis of biogenic amines, while the apo- open conformation, which exposes a wider protein surface and has more unstructured regions (loop2 and the flexible loop), is recognized by ubiquitin ligases and preferentially degraded by the ubiquitin proteasome system (UPS).