Enzymes involved in heme biosynthesis display subtle, tissue-specific variations; therefore, heme biosynthesis may be impeded in the liver, but normal in the immature red blood cells, or vice versa.
Other biochemical tests rely on the fact that heme precursors become less soluble in water (able to be dissolved in water) as they progress further through the heme biosynthesis pathway.
Making this determination yields a strong indicator of which enzyme in the heme biosynthesis pathway is defective; which, in turn, allows a diagnosis of the particular type of porphyria.
Owing to a defect in one of the enzymes of the heme biosynthesis pathway, protoporphyrins or porphyrins (heme precursors) are prevented from proceeding further along the pathway.
Although there are eight steps in heme biosynthesis, there are only seven types of porphyrias; a defect in ALA synthase activity does not have a corresponding porphyria.
Owing to deficient ferrochelatase, the last step in the heme biosynthesis pathway-the insertion of an iron atom into a porphyrin molecule-cannot be completed.
However, a glitch in the biosynthesis pathway-represented by a defective enzyme-means that heme biosynthesis does not reach completion.
Biosynthesis of heme is a multistep process that begins with simple molecules and ends with a large, complex heme molecule.
Heme is produced in several tissues in the body, but its primary biosynthesis sites are the liver and the bone marrow.
Porphyrias that affect heme biosynthesis in immature red blood cells were referred to as erythropoietic porphyries.