Porphyrin biosynthesis from ALA and PBG by human erythrocytes in porphyrin disorders. Kinetic studies of the isomer series I and III.
Porphyrin biosynthesis from exogenous ALA and PBG was observed over a period of from 1 to 8 hours in hemolysates of red blood cells from patients with AIP, PCT, and EPP. In all these conditions all porphyrins in the biosynthetic pathway through to PROTO were formed, with URO as the dominant component. Compared to normals, total porphyrin synthesis was lowered during the entire incubation period in both AIP and EPP, but enhanced in PCT. In hemolysates after 1 hour the second component of the pattern in AIP is COPRO, in PCT HEPTA and in EPP PROTO. Of the isomers, COPRO III predominates in all conditions (greater than 80%), whereas URO contains more isomer I than III. In intact red cells from controls, AIP, and PCT, COPRO is always the main component formed from ALA. Total synthesis is diminished in AIP by about 50%, in analogy to the findings on hemolysates from AIP. In heated hemolysates URO formation is diminished by half in AIP, but nearly double control values in PTC. In this sense URO'gen-I-synthase activity is increased in PCT. These findings reflect the underlying enzymatic defect: Diminished URO'gen-I-synthase activity in AIP, diminished URO'gen decarboxylase activity in PCT, and diminished activity of ferrochelatase in EPP.