Regulation of the genes for heme pathway enzymes in erythroid and in non-erythroid cells.

There are eight enzymes in the heme biosynthetic pathway and three enzymes in the heme catabolic pathway. Enzymatic defects in heme biosynthesis lead to clinical conditions termed porphyrias. cDNAs for five of the eight enzymes in the heme biosynthetic pathway and two of the three enzymes in the heme catabolic pathway have been cloned and characterized in mammalian cells. At least two enzymes exist as isozymes between erythroid and non-erythroid tissues. One is delta-aminolevulinic acid synthase (ALAS), and the erythroid and hepatic isozymes are coded by two separate genes. The other is porphobilinogen deaminase (PBGD), and both the erythroid and the non-erythroid PBGD mRNA are transcribed from a single PBGD gene by alternate transcription and splicing. There is also a significant tissue-specific control of expression of the uroporphyrinogen decarboxylase gene which is expressed as a unique mRNA in all tissues.