Sigrid Seubert

High-performance liquid chromatographic analysis of porphyrins and their isomers with radial compression columns☆

Abstract Porphyrin methyl esters and the isomers of uroporphyrin and heptacarboxylic porphyrin were separated by high-performance liquid chromatography. Isocoproporphyrin was also separated from coproporphyrin. By slight modifications to the solvent mixture, the separation of all biological polycarboxylic porphyrins was achieved. These separations were made possible through the high efficiency of 10- or 5-μm particle-size Radial-PAK cartridges, which have been used in the separation of porphyrins in various excreta and tissues in a number of porphyrias.

The biosynthesis of haem in congenital (erythropoietic) porphyria.

Abstract 1. 1. The enzymes of haem biosynthesis have been measured in peripheral blood in two patients aged 6 and 20 yr with congenital (erythropoietic) porphyria. 2. 2. Excessive activity of leucocyte δ-aminolaevulinic acid synthase was found in both patients. 3. 3. The activity of erythrocyte porphobilinogen deaminase was elevated and coupled with a lowered activity of uroporphyrinogen cosynthase, which resulted in excessive production of Series l isomer porphyrin. 4. 4. This was confirmed by isomer analysis of urine which showed an excess in both of coproporphyrin 1. 5. 5. Faecal porphyrin analysis demonstrated excessive quantities of ‘X’ porphyrin in one patient in common with other photosensitizing porphyrias. 6. 6. These results confirm that the primary control of haem biosynthesis in congenital porphyria is at the level of δ-aminolaevulinic acid synthase. with a secondary control point at the level of porphobilinogen deaminase.

Conversion products of hexachlorobenzene and their role in the disturbance of the porphyrin pathway in rats

Abstract 1. 1. Reactive conversion products of hexachlorobenzene and their role in the disturbance of the porphyrin pathway in female rats are reported. 2. 2. Following simultaneous application of hexachlorobenzene and mercury dichloride a comparatively earlier increase in the uroporphyrin content, connected with a decrease in the coproporphyrin content, was observed in the liver. 3. 3. Following application of labeled hexachlorobenzene, liver cytosol proteins, precipitated by trichloroacetic acid, were found to bind labeled carbon derived from hexachlorobenzene. 4. 4. Repeated application of hexachlorobenzene led to a decrease in the activity of a cytosolic glutathione S-transferase, which catalyzes the conversion of 1,2-epoxy-3-( p -nitrophenoxy)propane. 5. 5. From these results we concluded that reactive conversion products of hexachlorobenzene are formed in the liver. Their binding to proteins supports the hypothesis that the disturbance of the uroporphyrinogen decarboxylase function may be due to covalently binding conversion products of hexachlorobenzene. The inhibition of the glutathione S-transferase may indicate that the transfer of sulphur is associated on one hand with the detoxification of hexachlorobenzene and on the other hand with the function of the uroporphyrinogen decarboxylase, an enzyme with essential SH-groups.

Natural Rubber Latex Allergy Is Not a Cause of Sudden Infant Death

Background: The causes for sudden infant death (SID) remain unclear. As infants can become sensitized to NRL allergens by pacifiers and latex mattresses, we tried to establish whether there is a relationship between SID and natural rubber latex (NRL) allergy. Methods: We determined NRL–specific IgE concentrations in 112 unselected cases of SID by the CAP–FEIA method. Results: NRL–specific IgE could be detected only in 1 sample (0.64 kU/l; CAP class 1). Conclusions: We conclude that NRL allergy is not a cause of SID.

Porphyria erythropoetica congenita Günther und Chloroquin

SummaryTreatment of a six-years old boy with porphyria congenita (Günther) by small amounts of chloroquine was followed by a sharp but transient increase of the urinary excretion of porphyrins. Moreover, a nearly complete normalization of the previously observed rigidity of the erythrocytes occurred. With respect to the possibility that this elevated rigidity plays an important role for the typical hemolysis connected with this porphyria, the application of chloroquine could be of therapeutic value for this disease.ZusammenfassungBei einem 6jährigen Jungen mit Porphyria congenita Günther kam es unter Chloroquin in niedriger Dosierung zu einem vorübergehenden erheblichen Anstieg der Porphyrin-Ausscheidung mit dem Urin und vor allem zu einer weitgehenden Normalisierung der vorher pathologischen Rigidität der Erythrozyten. Da eine solche Rigidität der Erythrozyten bei der für diese Porphyrie typischen Hämolyse eine wesentliche Rolle spielen dürfte, könnte die Chloroquin-Anwendung therapeutisch wertvoll sein.

Elimination of porphyrins and their precursors in rats pretreated with hexabromobenzene

The elimination times of porphyrins and their precursors and of hexabromobenzene (HBB) itself were studied in female rats given 15 mg HBB by stomach tube every other day for 4 months. The concentrations of HBB in the blood, liver and adipose tissue were in the ratio 1:1.5:25, 24 hr after the last dose. Two weeks after the end of treatment, HBB was no longer detectable in the tissues. In animals given a single oral dose of 16.6 mg HBB/kg body weight, HBB was no longer detectable in adipose tissue 12 days after dosing. The half-life of HBB in adipose tissue was about 2.5 days in the animals given HBB for 4 months, and at the end of the treatment the concentrations of porphyrin in the liver, urine and faeces were increased to about 1000, 600-700 and 60-70 times the control values. The amounts of delta-aminolaevulinic acid and porphobilinogen in the urine of treated animals were 6-7 times those in controls. After the end of HBB treatment, it took almost 1.5 yr for delta-aminolaevulinic acid and porphobilinogen excretion to return to normal. Nearly 2 yr were needed for complete elimination of the accumulated liver porphyrins.

High-performance liquid chromatographic analysis of porphyrins and their isomers with radial compression columns.

Publisher Summary This chapter discusses high-performance liquid chromatographic analysis of porphyrins and their isomers with radial compression columns, and describes the two methods for the separation of porphyrin methyl esters and their isomers. One method makes possible the separation of porphyrins with two to eight carboxylic groups in a short time. The other method allows, in addition to this differentiation, a separation of the isomers of uroporphyrin and heptacarboxy porphyrin. This method requires significantly more time. For the separation two systems are employed: system 1 and system 2. The separation of porphyrins in the hemofiltrate is a very helpful diagnostic tool. The baseline separation of the porphyrins with 4, 5, 6, 7, and 8 carboxylic groups in a hemofiltrate is shown. System 1 and fluorescence detection were used. Mainly uroporphyrin and heptacarboxyporphyrin can be seen. The separation of porphyrins in the investigation of the enzymes of heme biosynthesis is helpful. Determination of the uroporphyrinogen decarboxylase activity in human erythrocytes shows considerable variations in the distribution of the decarboxylation products by using uroporphyrinogen I and III. Uroporphyrinogen I is more slowly decarboxylated than uroporphyrinogen III. The enzymatic decarboxylation of uroporphyrinogen III yields about 51% coproporphyrin, in addition to 23% heptacarboxyporphyrin and 11% penta- and hexacarboxyporphyrin. From uroporphyrinogen I only 21% coproporphyrin and 15% hepta-, hexa-, and pentacarboxyporphyrin are produced. Determination of the isomer porphyrins is of interest. The separation of the I and III isomers of uroporphyrin and heptacarboxyporphyrin is performed with System 2. The distribution pattern of porphyrins in feces of a hexachlorobenzene- poisoned rat is shown in the chapter.

Epidemiological study on the relationships between lead exposure and porphyrin metabolism

Abstract 1. 1. In 314 lead workers, blood lead, erythrocyte porphyrins as well as urinary 5-aminolevulinic acid and urinary porphyrins were determined. A person exposed to lead for the first time was investigated over a period of 28 months. Diurnal variations in the bioparameters were shown with reference to two examples. 2. 2. In 53 subjects not exposed to lead, the seasonal range of the individual parameters is shown.