porphobilinogen

Porphobilinogen, abbreviated PBG, is a colorless pyrrole derivative and an essential intermediate in the biosynthesis of heme and other tetrapyrroles. It is produced in the cytosol during the early steps of porphyrin synthesis.

In the biosynthetic pathway, two molecules of δ-aminolevulinic acid (ALA) are condensed by the enzyme ALA dehydratase (porphobilinogen synthase) to form porphobilinogen. Four molecules of PBG are then linked by porphobilinogen deaminase (hydroxymethylbilane synthase) to generate hydroxymethylbilane, which is converted further into uroporphyrinogen III and proceeds toward heme production.

Clinically, PBG is an important diagnostic metabolite. It is present in all tissues and in urine, and elevated urinary PBG (often with increased ALA) is a hallmark of acute porphyrias, particularly acute intermittent porphyria (caused by deficiency of porphobilinogen deaminase) and other hepatic porphyrias. The accumulation of PBG can be associated with neurovisceral symptoms, abdominal pain, and neuropsychiatric changes. Laboratories screen for PBG using methods such as the Ehrlich’s reagent test and chromatographic techniques; confirmatory testing can involve high-performance liquid chromatography or mass spectrometry.

Thus, porphobilinogen occupies a pivotal role as an early precursor in heme biosynthesis and as a key biomarker in the diagnosis of porphyrias.