Diagnostic Techniques and Surgical Management of Brain Tumors 228 2. 5-ALA metabolic pathway 2.1 5-ALA metabolism in normal cells 5-ALA is a substance that naturally exists in the body. In the first stage, 5-Ala is produced via the condensation of glycine and succinyl-CoA by ALA synthetase (ALAS) in the mitochondria. This process receives negative feedback from heme, which is the endproduct. 5-ALA is actively transported via cytoplasm. In the next step, porphobilinogen (PBG) is created from ALA via ALA dehydratase. The actions of PBG deaminase (PBGD) and uroporphyrinogen III synthase compress 4 PBG molecules, effectively cyclizing a tetrapyrrole chain and producing uroporphyrinogen III. Uroporphyrinogen III is converted by uroporphyrinogen decarboxylase into coproporphyrinogen III, which is exposed to coproporphyrinogen oxidase in the mitochondrial intermembrane space. Decarboxylation and oxidation of the propionic side chains of the vinyl groups' rings A and B ultimately form protoporphyrinogen IX in the cell nucleus. PpIX is synthesized from protoporphyrinogen IX via protoporphyrinogen oxidase activity, and heme is synthesized via the uptake of iron into the tetrapyrrole structure by ferrochelatase in the mitochondrial membrane ( Fig.