Tetrapolymerization of the monopyrrole PBG into the hydroxymethylbilane pre-uroporphyrinogen in several discrete steps. H2O + 4 porphobilinogen = hydroxymethylbilane + 4 NH4(+) Binds 1 dipyrromethane group covalently. Inhibited by NH(3), heavy-metal ions, hydroxylamine and 2-bromoporphobilinogen. Not inhibited by N-ethylmaleimide. Optimum pH is 7.7-8.5. Heat stable and fully active up to 70 degrees Celsius. Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 2/4. Porphyrin-containing compound metabolism; chlorophyll biosynthesis. Monomer. The porphobilinogen subunits are added sequentially to the dipyrromethane cofactor that is covalently attached to the enzyme. The last step of the reaction involves the hydrolysis of the bound polypyrrole chain and the release of hydroxymethylbilane. Belongs to the HMBS family.