Porphyrin metabolism, abnormal

Aplastic anemia and leukemia are not the only health effects ascribed to benzene exposure. A number of recent studies have associated benzene exposure with chromosomal changes (aberrations) (118). Other studies have shown abnormalities in porphyrin metabolism and decrease in leucocyte alkaline phosphatase activity in apparendy healthy workers exposed to 10—20 ppm benzene (119,120). Increases in leukoagglutinins, as well as increases in blood fibrinolytic activity, have also been reported and are believed to be responsible for the persistent hemorrhages in chronic benzene poisoning (121,122). 

Pseudoporphyria is a photodistributed bullous disorder with clinical and histological features similar to those of porphyria cutanea tarda, but without accompanying abnormalities of porphyrin metabolism. Drugs, in particular NSAIDs and sulfur-containing diuretics, often cause pseudoporphyria (193). Pseudoporphyria associated with naproxen (15 mg/kg/day) has been reported in a child (194). 

Abnormalities of porphyrin metabolism are caused by inherited defects in the genes of the biosynthetic pathway enzymes, diseases called the porphyrias, or by conditions (e.g., lead toxicity) that affect the enzymatic activity in subjects with normal heme synthesis genes. 

Abnormalities of porphyrin metabolism, excretion, or both may occur in the absence of porphyria caused by a number of other diseases that need to be considered when interpreting data from patients in whom porphyria is suspected. ... 

McCoU KEL, Godberg A. Abnormal porphyrin metabolism in diseases other than porphyria. Clinics in Haematology 1980 9 427-45. 

K.E. Anderson (1990). Erythrocyte disorders diseases related to abnormal heme or porphyrin metabolism. In W.J. Williams, E. Beutler, A.J. Erslev, M.A. Lichtman (Eds), Hematology, 4th Edn., (pp. 722-741). McGraw-Hill, New York. 

Piomelli S, Seaman C, Kapoor S (1987) Lead-induced abnormalities of porphyrin metabolism. The relationship with iron deficiency. Ann N Y Acad Sci 514 278-288... 

The porphyrias are a group of diseases in which disturbances of porphyrin metabolism occur either as inherited or acquired abnormalities. They are classified into the so-called erythropoietic and hepatic forms according to the chemical evidence of the primary site of the metabolic defect [63], and it is the second, hepatic group which mainly concerns us here in this discussion on neuropathies. 

Heavy metals stimulate or inhibit a wide variety of enzyme systems (16, 71, 72), sometimes for protracted periods (71, 73). These effects may be so sensitive as to precede overt toxicity as in the case of lead-induced inhibition of 8 ALA dehydrase activity with consequential interference of heme and porphyrin synthesis (15, 16). Urinary excretion of 8 ALA is also a sensitive indicator of lead absorption (74). Another erythrocytic enzyme, glucose-6-phosphatase, when present in abnormally low amounts, may increase susceptibility to lead intoxication (75), and for this reason, screens to detect such affected persons in lead-related injuries have been suggested (76). Biochemical bases for trace element toxicity have been described for the heavy metals (16), selenium (77), fluoride (78), and cobalt (79). Heavy metal metabolic injury, in addition to producing primary toxicity, can adversely alter drug detoxification mechanisms (80, 81), with possible secondary consequences for that portion of the population on medication. 

Gibson GE, McGinnity E, McGrath PM, Carmody M, Walshe J, Donohoe J, et al. Cutaneous abnormalities and metabolic disturbance of porphyrins in patients on maintenance dialysis. Clin Exp Dermatol 1997 22 124-7. 

The basic concept upon which ALA-PDT is based was conceived as we studied the biochemical basis for the group of metabolic diseases known as the porphyrias [43]. Some of the porphyrias are associated with a generalized photosensitization which is caused by the accumulation of specific types of porphyrin in the blood and/or tissues, where each type of porphyrin accumulates as the result of a specific abnormality in the biosynthetic pathway for heme. Although at that time it was generally believed that the expression of such abnormalities was restricted to the liver and the hemopoietic system (those tissues which synthesize large amounts of heme), it was obvious that all nucleated cells must have at least some capacity to synthesize heme because they all use heme-containing enzymes for the tricarboxylic acid cycle. 

The porphyrins are intermediates in the biosynthesis of haem and chlorophyll and are thus responsible for the most abundant colors in nature. Small amounts of porphyrins can be isolated from normal urine and feces, although certain metabolic disorders cause abnormally high concentrations of some of these pigments. 

With the recognition that there is abnormal excretion of certain porphyrins in the hereditary porphyrias it was assumed that as in other metabolic errors, the abnormalities resulted from an enzyme block either in an associated pathway diverting more substrate to porphyrin synthesis or in porphyrin utilization leading to an accumulation of metabolic precursors. However, further observations showed that neither of these hypotheses was tenable. 

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