Porphyrin Synthesis from 5-Aminolevulinic Acid in Patients with Glioma

The molecule 5-aminolevulinic acid (5-ALA) is a substrate for a heme synthesized in cells us‐ ing succinyl CoA and glycine. Initially, 5-ALA is converted to porphobilinogen (PBG), and the metabolism progresses by the action of PBG deaminase, and its product is incorporated into the mitochondria via uroporphyrinogen and coproporphyrinogen by an enzymatic reaction and transformed into protoporphyrin IX (PPIX). This PPIX is then converted to a heme by the action of ferrochelatase. These metabolic reactions are conducted in the liver and erythroblasts of normal human subjects [16]. It is thought that a larger amount of 5-ALA is incorporated by rapidly proliferating tumor cells as compared to normal cells, due to the active synthesis of heme [5, 20]. In the metabolic pathway of 5-ALA, it is reported that the rate limiting enzyme in normal cells is different from that in tumor cells [16]. PBG deaminase is the rate limiting en‐ zyme in normal cells [3]. Large amounts of uroporphyrinogen, coproporphyrinogen, and PPIX are produced in tumor cells compared to normal cells because metabolism after the PBG is pro‐ moted by high PBG deaminase activity and low ferrochelatase activity [15]. The PPIX accumu‐ lates in tumor cells and produces a red fluorescent response to ultraviolet light. Intraoperative photodynamic diagnosis using this method is used for patients with glioma [21, 24, 26]. There are numerous reports concerning the PPIX concentration in the tumor tissue; however, re‐ ports concerning plasma titers and urinary excretion of uroporphyrinogen and copropor‐ phyrinogen after 5-ALA administration are rare [25]. In this study, 5-ALA was administered to healthy adult volunteers, and changes in serum and urinary porphyrins were measured. Uri‐ nary excretion of porphyrins in volunteers and patients with brain tumors after the 5-ALA ad‐ ministration were compared and examined.