Porphyria porphyrin metabolism

Because hexachlorobenzene can interfere with porphyrin metabolism and produce chemical porphyria, the evaluation of the urinary porphyrin pattern has been proposed as an early biomarker of effect (San Martin et al., 1977 Schmid, I960, 1966 Wray et al., 1962). However, apart from an outbreak of chemical porphyria which occurred in Turkey in the 1950s following ingestion of hexachlorobenzene-contaminated food, cases of chemical porphyria among... 

The porphyrias are a heterogeneous group of diseases of porphyrin metabolism characterized by a variety of dermatologic, neurologic, and psychological manifestations. 

Griseofulvin interferes with porphyrin metabolism. In man, transient increases in erythrocyte protoporphyrin concentrations have been demonstrated, and the production and excretion of porphyrins is increased. Acute intermittent porphyria is an absolute contraindication to griseofulvin. In patients with other forms of porphyria it should also be avoided, in view of the many alternatives (458-463). 

Herrick, A., McLellan, A., Brodie, M.J., McColl, K.E.L., Moore, M.R., Goldberg, A. Effect of haem arginate therapy on porphyrin metabolism and mixed function oxygenase activity in acute hepatic porphyria. Lancet 1987/11 1178—1179... 

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. 

Thunell S, Harper P, Brock A, Peterson NE. Porphyrins, porphyrin metabolism and porphyrias. II. Diagnosis and monitoring in the acute porphyrias. Scan J Clin Lab Invest 2000 60 541-59. 

Porphyria Any of a number of diseases characterized by derangement in porphyrin metabolism many are caused by genetic defects in the biosynthetic enzymes. 

Thunell, S. (2000) Porphyrins, porphyrin metabolism and porphyrias. I. Update, Scand. J. Clin. Lab Invest, 60 509-540. 

In 1956, it was reported that of four volunteers who ingested ALA as part of a study of porphyrin metabolism, those who took the largest doses experienced transient photosensitization of the skin [105,106]. These experiments took place at a time when it was generally believed that the capacity for excessive synthesis of porphyrins was restricted to the liver and the bone marrow, because it was these organs which produced the porphyrins responsible for the skin photosensitization associated with certain types of porphyria [107]. Consequently, the skin photosensitization induced by ingestion of ALA was interpreted in similar terms. Despite this erroneous assumption about the mechanism involved, these researchers had established that systemic administration of ALA to humans could cause skin photosensitization. We verified these observations in mice given ALA... 

The next step in heme biosynthesis, is the condensation of two molecules of ALA, via the enzyme ALA dehydratase, to give the pyrrole called porphobilinogen or PBG. This compound was first identified in the urine of patients suffering from one of a family of diseases of porphyrin metabolism, called porphyrias. Labelled PBG has been efficiently incorporated into heme using chicken blood as the biosynthetic model system. What is interesting about the biosynthesis of PBG is that it is very similar... 

Interestingly, both the light sensitivity caused by certain porphyrias, and the use of UV light to destroy bilirubin involve the sensitisation of oxygen into an electronically excited state, where it is much more reactive. Before we examine some of the pathological states that arise from faulty porphyrin metabolism therefore, we shall make a short digression to discuss the photophysics of oxygen. 

As if to emphasize our complete dependency on these pigments of hfe, strange disorders called porphyrias afflict those with faulty porphyrin metabolism. Such disorders can cause severe light sensitivity and even insanity. King George III may have owed his notorious irascibility and eventual madness to porphyria. There is even the possibUity that those mythical denizens of the night, vampires, could have been sufferers of a rare form of this condition. 

Porphyrin Metabolism and Porphyria 201 Chemistry of Porphyrins Biosynthesis of Porphyrins Heme Synthesis... 

The metabolic alterations are restricted to liver porphyrin metabolism. There are no changes in porphyrin biosynthesis in bone marrow and no hematological changes. The biochemical lesions in the intermittent type of porphyria are probably different from that responsible for erythropoietic porphyria, since in the intermittent type mainly a-amino levulinic acid and porphobilinogen accumulate, whereas mainly uroporphyrin I accumulates in erythropoietic porphyria. The lesions that develop in acute intermittent porphyria could result either from a lack of porphobilinogen use for further metabolic conversion or from an overproduction of a-amino levulinic acid or porphobilinogen. 

The porphyrias may be defined as inheritable diseases of porphyrin metabolism. Waldenstrom s classification of these diseases will be Waldenstrom, J., Acta Med. Scand. Suppl. 82 (1937). 

Many small molecules of clinical interest can be detected by fluorescence. For example, porphyrins, which are intermediates in the metabolism of iron-containing heme prosthetic groups, can be detected and quantitated in urine by reversed-phase chromatography followed by fluorometric detection, exploiting the natural fluorescence of porphyrin compounds [18]. An example of reversed-phase chromatography for a mixture of carboxylated porphyrin precursors is demonstrated in Figure 21.2. The relative abundances of different porphyrin compounds can aid in diagnosing porphyria, which is a term that describes the collection of disorders caused by defects in the enzymes responsible for porphyrin metabolism. 

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