L. Eriksen

THE ETHER SOLUBLE PORPHYRINS FOUND IN THE URINE OF NORMAL MAN AND RABBIT

In a paper presented at the IV International Congress of Biochemistry (Eriksen, 1958 a) evidence was presented indicating that at least 3 different coproporphyrins, chromatographically behaving like the II, III (1V) and I isomers of coproporphyrin, were present in the urine of normal man and rabbit. The main isomer found in both man and rabbit was the 111 isomer, smaller amounts of the I isomer and trace amounts of a coproporphyrin behaving as the II isomer.

Paper Chromatography of Porphyrin Pigments

1. A simple and time-sparing procedure for the paper chromatographic separation of porphyrin pigments has been described.2. 2–6 lutidine, which is completely miscible with water at temperatures up to 40o C, has been found to be easier to handle than the 2–4/2–5 lutidine used by Nicholas & Rimington (1949, 1951).3. In contrast to the findings of Nicholas & Rimington (1951), a system containing NH3 vapor is found to give better separation of the porphyrins.

The Nature of the Intermediate Tetrapyrroles in Protoporphyrin and Heme Biosynthesis

The main porphyrins found in nature apart from protoporphyrin and derivatives of this compound are uroporphyrin and coproporphyrin, having 8 and 4 carboxylic groups respectively. The relation of these porphyrins to heme biosynthesis has been debated for some time, and in 1950 Radin, Rittenberg and Shemin & Neuberger, Muir & Gray suggested that protoporphyrin was formed from uroporphyrin by stepwise de-carboxylation and dehydrogenation. However, the experimental evidence for such a mechanism was rather incomplete.A coproporphyrin precursor behaving chromatographically as a 3 carboxylic porphyrin has been found in extracts from rabbit reticulocytes after incubation of the cells under hypoxic conditions.The nature of this precursor has been discussed, and evidence that we are dealing with a partially oxidized coproporphyrinogen has been presented.It is suggested that the first step in the conversion of coproporphyrinogen into protoporphyrin is a partial oxidation of the por-phyrinogen prior to the final deca...

CONGENITAL ERYTHROPOIETIC PORPHYRIA WITH A HITHERTO UNDESCRIBED PORPHYRIN PATTERN

One proven and one probable case of CEP in second cousins from Northern Norway are reported. The porphyrin pattern in Case 1, who has been studied extensively, in certain respects differs from that reported earlier in CEP, indicating that the disease may be genetically heterogeneous. The most impressive finding is the extraordinary high amounts of 7 carboxylic porphyrin in urine. Isomer analysis has shown this porphyrin to belong to the isomer III series. The presence of increased amounts of protoporphyrin in plasma and feces is also at variance with the picture seen in classical CEP.

Urinary excretion of position isomers of penta-and hexa-carboxylated porphyrins belonging to the isomer III series in a case of congenital erythropoietic porphyrin

The excretion of position isomers of penta- and hexa-carboxylated porphyrins type III in the urine in a case of congenital erythropoietic porphyria characterized by the excretion of large amounts of penta-, hexa- and hepta-carboxylated porphyrins type III together with isocoproporphyrins both in the urine and faeces, and a simple method for the synthesis and separation of such position isomers has been described. The implications of the finding of position isomers type III have been discussed and it is suggested that the decarboxylation of uroporphyrinogen III both in the present case and under physiological conditions is a random process.

Porphyrin Distribution and Porphyrin Excretion in Human Congenital Erythropoietic Porphyria

A study of the excretion pattern and porphyrin distribution in a case of congenital erythropoietic porphyria has been presented. More than 50% of the porphyrins excreted in the urine are type III isomers, most of which are found in the hepta-, hexa- and pentacarboxylic porphyrins. A tetracarboxylic porphyrin having 3 propionic and 1 acetic acid β-chains and with chromatographic and spectral properties similar to isocoproporphyrin has been found to be excreted in both faeces and urine. This porphyrin seems to be preferentially excreted in the urine. The erythrocytes contain almost entirely protoporphyrin, while the ‘buffy coat’ and bone marrow contain predominantly octa- and heptacarboxylic porphyrins. The pattern found in liver and plasma differs from that of bone marrow and ‘buffy coat’ primarily in showing exceptionally large amounts of an apparent hexacarboxylic porphyrin, while the spleen contains relatively high amounts of uroporphyrin. Trace amounts of an apparent isocoproporphyrin are found in bone...

CONGENITAL ERYTHROPOIETIC PORPHYRIA: The Effect of Light Shielding

The effect of various types of measures taken for light shielding against daylight in a recently detected case of CEP, has been followed for more than a year. It has been found that the celluloid film, “Para‐Sol”, which has a good translucency for wavelengths above 550 nm, but is not translucent to wavelengths below 510 nm, not only removes the troublesome skin lesions seen in this disease, but also. brings about an almost complete compensation of the anemia, disappearance of the splenomegaly and marked changes in the blood and urinary porphyrin patterns. In blood the erythrocyte porphyrins change from predominantly proto‐porphyrin with trace amounts of copro‐ and not detectable uroporphyrin, to high amounts of both proto‐, copro‐ and uroporphyrins. The plasma porphyrins remain essentially unchanged. The urinary pattern changes from predominantly free porphyrins to predominantly porphyrinogens.

THE EFFECT OF VARIOUS THERAPEUTIC TRIALS ON THE PORPHYRIN EXCRETION IN A CASE OF CONGENITAL ERYTHROPOIETIC PORPHYRIA

ABSTRACT: Eriksen, L. and Seip, M. (Institute of Physiology, University of Oslo, and Department of Pediatrics, University Hospital, Oslo, Norway). The effect of various therapeutic trials on the porphyrin excretion in a case of congenital erythropoietic porphyria. Acta Paediatr Scand 64:287, 1975.–A patient with a biochemically “new” type of congenital erythropoietic porphyria has been studied under various therapeutic trials. Splenectomy had no demonstrable effect on porphyrin excretion or clinical picture. Vitamin E caused a moderate fall in porphyrin excretion, however, there was no significant improvement in light tolerance and tendency to hemolysis. β‐carotene reduced skin photosensitivity appreciably, while total porphyrin excretion remained unchanged and the tendency to develop hemolytic anemia showed only slight improvement. Red cell transfusion caused a rapid, dramatic fall in porphyrin excretion (in 4–5 days) and a transient increase in light tolerance, while the distribution of the different porphyrins excreted remained unchanged. These observations indicate that all or nearly all the abnormal porphyrins excreted are of erythropoietic origin, and that the overwhelming part of the porphyrins originate from an abnormal population of shortlived red cells. Findings on fluorescence microscopy of blood and bone marrow support this view. Meticulous protection against light of the shorter wavelengths caused a similar rise in hemoglobin level as produced by red cell transfusion, however, in this instance the total excretion of porphyrins did not fall. It is suggested that the inhibitory effect of transfusion on erythropoiesis (and thereby porphyrin excretion) might be due partly to a depression of erythropoietin formation, partly to the presence of an erythropoiesis inhibiting factor (chalone) in the transfused red cells.

The Ether Soluble Porphyrins Found in Urine in Acute Porphyria and Porphyria Cutanea Tarda

1. The ether soluble porphyrins in the urine of one case of porphyria cutanea tarda and two cases of acute porphyria have been studied and compared with the ether soluble porphyrins from normal man, and it has been shown that the porphyrin pattern in porphyria cutanea tarda differs from that of acute porphyria and normal man in that the amounts of porphyrins with 5-7 carboxylic2. The isomer pattern of coproporphyrin has been found to be the same in all conditions studied. The main isomer is the III isomer, with approximately 40 per cent I isomer and trace amounts of a porphyrin behaving like the II isomer of coproporphyrin.3. The 3 and 5 carboxylic porphyrins have each been split by paper chromatography into two distinct spots with approximately the same amount of porphyrin in each spot.4. The possible implication of these findings have been discussed, and it is suggested that the coproprphyrin isomer pattern found is due to the isomerization of excess formed coproporphyrinogen III during the biosynthesis...

Urinary excretion of porphyrins in two cases of porphyria cutanea tarda during a period of various treatments

The urinary excretion of porphyrins in two cases of porphyria cutanea tarda (PCT) has been followed during a period in which various treatments have been tried. In one patient pyridoxal-5-phosphate (P-5-P) injections lead to a dramatic increase in porphyrin excretion. In another P-5-P treatment was followed by a significant decrease in porphyrin excretion. p-Aminobenzoic acid (PABA) apparently had no effect on porphyrin excretion, while repeated phlebotomies had the expected effect. In both patients all variations in the total amount of porphyrins excreted were almost exclusively due to the variations in the amounts of heptacarboxylic porphyrin type III and uroporphyrin I. A secondary finding was an increase in hexa- and penta-carboxylic porphyrins type III without a concomitant increase in coproporphyrin III.