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The pathway begins in the mitochondrial matrix with the rate-limiting reaction catalyzed by 5-aminolevulinic acid synthase (ALAS), a PLP-dependent homodimeric enzyme that condenses succinyl-CoA and glycine to produce 5-aminolevulinic acid (ALA), releasing CO and CoASH

The lack of carcinogenic activity of 2-hydroxyestrogens has been attributed to a high rate of clearance, more rapid rate of O -methylation and lower hormonal potency in estrogen target tissues, plus produces 2-methoxyestradiol, which suppress tumor cell proliferation and angiogenesis [19]