Abstract

One or two ways in which porphyrin metabolism might be disturbed, such as disturbances of the formation and breakdown of myoglobin or of the cytochromes, have not been mentioned, because there is little or no evidence whether drugs affect them. Most of the known disturbances of porphyrin metabolism involve either haemopoiesis or liver function. Lead poisoning is clearly in the first category, poisoning by Sedormid and other substances containing allyl groups in the second. The mild porphyrinuria produced by aromatic amines and nitro-compounds may be due to abnormal haemoglobin breakdown, but seems more likely to be comparable to the effect of lead. The dyshaemopoietic porphyrinurias can be conceived simply as due to blockage at one or more stages of the normal synthesis of iron-protoporphyrin, so that intermediaries or products of diverted metabolism such as coproporphyrin appear in excess. Details about the stage of blockage have still to be worked out. The porphyrinurias associated with changes in the liver are less comprehensible. They may involve abnormal formation or destruction of iron-porphyrin compounds which are synthesized by a mechanism different from the haemopoietic one, and so susceptible to damage by different agents; or they may arise through some as yet undetermined influence of the liver on haemopoiesis, for example, in synthesizing, excreting or failing to excrete some essential intermediary metabolite. The particular porphyrins which appear in the urine are not diagnostic of the site of the disturbance; porphobilinogen and uroporphyrin appear after Sedormid and after the combination of phenylhydrazine, lead and light and coproporphyrin appears both when the liver is diseased, and after interference with haemopoiesis by lead. The isomeric type is also not diagnostic. There is a connexion between coproporphyrin I excretion and increased haemopoiesis and coproporphyrin III excretion and obstructed haemopoiesis, but with the uroporphyrinurias and in liver disease there is a notable variability in the isomer type in any particular condition. The most promising developments now appear to be in the study of isolated tissue systems or homogenates, in the further investigation of precursors and the conditions under which they form free porphyrins, and in examining in more detail the actions of drugs on the tissue porphyrins as well as on the porphyrins excreted by experimental animals.