The UPS locus encoding uroporphyrinogen I synthase is located on human chromosome 11.

The expression of the UPS locus encoding uroporphyrinogen I synthase has been investigated in human/mouse somatic cell hybrids. Human and mouse uroporphyrinogen I synthase can be readily distinguished by their isoelectric points. In hybrid cells, both human and mouse isozymes are detected. The multiple human uroporphyrinogen I synthase isozymes segregate as a single unit, as expected if they are the products of a single locus. The absence of new heteropolymers in hybrid cells supports the biochemical evidence that the active enzyme is a monomer. The presence of human uroporphyrinogen I synthase in hybrid clones was correlated with the presence of human chromosome 11, or its enzymatic marker, without exception in 44 independent hybrid lines. All other chromosomes could be eliminated as possible locations for this locus, due to their independent segregation. This report represents the first gene assignment for an enzyme in the heme biosynthesis pathway. Uroporphyrinogen I synthase (EC 4.3.1.8) is the third enzyme in the pathway leading to the biosynthesis of heme. Partial deficiency of this enzyme is associated with the human disorder Acute Intermittent Porphyria, an autosomal dominant inherited disease (1). Deficiencies of the other enzymes of heme biosynthesis also produce dominantly-inherited disorders (1). Chromosomal linkage data for these enzymes would make possible improved diagnosis of these disorders through the analysis of closely-linked genetic markers. The linkage relationships among these functionally related enzymes would also be of interest. We have recently described a simple isoelectric focusing method for the analysis of uroporphyrinogen I synthase isozymes in tissue extracts (2). Human and mouse tissues contain multiple isozymes, and additional erythrocyte specific isozymes are present in both species. These isozymes have recently This work was supported by Contract E (11-l) (2828) from the U.S. Department of Energy and by USPHS Grants GM 24812, GM 20454 and HD 05196.