Porphyrins are the only and most powerful
photosensitizers synthesized internally. To understand better the involvement of
porphyrins in
photosensitization reactions, the
heme biosynthetic pathway is first described, as well as the main features of its regulation in both erythroid and hepatic cells. Most disorders of
porphyrin metabolism, known as
porphyrias, are characterized by
porphyrin accumulation. A full discussion of these diseases, their classification and relevant biochemical and clinical signs are presented. Abnormalities in
heme biosynthesis in disorders other than
porphyrias, such as
iron-deficient and
sideroblastic anemias,
lead poisoning,
hereditary tyrosinemia,
chronic renal disease and
alcoholism, are briefly considered. A complete survey of the experimental research on the biosynthesis of
porphyrins in
tumors and of the important association between
cancer and
porphyrias is dealt with. The link to
photodynamic therapy (
PDT) emerges naturally and this is treated from the point of view of using
porphyrins endogenously formed by the
tumors for their localization and
PDT. Finally, considering the nature of the alterations occurring in
heme metabolism in
tumors, and
porphyrias and their ubiquity, a model is discussed where the abnormality of
heme synthesis is involved in the initiating lesion of
carcinogenesis. The model strongly predicts that the incidence of
cancer will be high in cells with abnormal
heme metabolism, suggesting that porphyric patients may be at greater risk of the development of
cancer.