Coproporfiria hereditaria. Estudios bioquímicos en 7 pacientes sintomáticos y familiares / Coproporphyria heredity. Studies biochemistry in 7 patients sintomatics and familiaries

Se han estudiado 7 pacientes con coproporfiria herediatria (CPH) sintomática: en 6 de ellos se investigaron 14 familiares consanguíneos. Tres de los siete (43 por ciento) pacientes exhibián signos cutáneos hiperpigmentación, fotosensibilidad, y/o máculas y todos presentaron ataques neuroviscerales. Desde el punto de vista bioquímico los pacientes excretaban niveles elevados de precursores y/o porfirinas en orina ácido 5-aminoleválico (ALA) (3,9 - 14,1 mg/24h), porfobilinógeno (PBG) (6,5 - 47,9 mg/24h), porfirinas totales (645-31129 mug/24h), que disminuyeron alcanzada la remisión (ALA: 0,2 - 5,3 mg/24h: PBG: 0,8 -25,2 mg/25,2 mg/24h, porfirinas totales 112-952 mu/24h, valor normal: ALA 2-4 mg/24h: PBG: 1-2 mg/24h. Porfirinas 20-250 mug/24h). Las profirinas fecales también estuvieron incrementadas la fase aguda (316-50.056 mug/g seco) y en remisión (165-1600) mug/g seco) valor normal <= 130 mu/g seco. El patrón de excreción de porfirinas urinarias y fecales mostró siempre una elevada concentración de coproporfirinas, la longitud de onda de emisión (618 nm) de las porfirinas plasmáticas permitió identificar la porfiria como una CPH y distinguirla de la porfiria variegata (PV). El tratamiento del ataque agudo de la CPH fue semejante al empleado en los casos de porfiria aguda intermitente o PV carbohidratos (ataques agudos 300- 500 g/diarios, ataques leves 20 - 40 g/diarios) complejo vitamínico B y ácido fólico (30 mg/día). Cuando los pacientes presentaron signos clínicos cutáneos se administró S-adenosil-L-metionina 12 mg/kg/día durante 3 semanas.(AU)

Coproporfiria hereditaria. Estudios bioquímicos en 7 pacientes sintomáticos y familiares / Coproporphyria heredity. Studies biochemistry in 7 patients sintomatics and familiaries

Se han estudiado 7 pacientes con coproporfiria herediatria (CPH) sintomática: en 6 de ellos se investigaron 14 familiares consanguíneos. Tres de los siete (43 por ciento) pacientes exhibián signos cutáneos hiperpigmentación, fotosensibilidad, y/o máculas y todos presentaron ataques neuroviscerales. Desde el punto de vista bioquímico los pacientes excretaban niveles elevados de precursores y/o porfirinas en orina ácido 5-aminoleválico (ALA) (3,9 - 14,1 mg/24h), porfobilinógeno (PBG) (6,5 - 47,9 mg/24h), porfirinas totales (645-31129 mug/24h), que disminuyeron alcanzada la remisión (ALA: 0,2 - 5,3 mg/24h: PBG: 0,8 -25,2 mg/25,2 mg/24h, porfirinas totales 112-952 mu/24h, valor normal: ALA 2-4 mg/24h: PBG: 1-2 mg/24h. Porfirinas 20-250 mug/24h). Las profirinas fecales también estuvieron incrementadas la fase aguda (316-50.056 mug/g seco) y en remisión (165-1600) mug/g seco) valor normal <= 130 mu/g seco. El patrón de excreción de porfirinas urinarias y fecales mostró siempre una elevada concentración de coproporfirinas, la longitud de onda de emisión (618 nm) de las porfirinas plasmáticas permitió identificar la porfiria como una CPH y distinguirla de la porfiria variegata (PV). El tratamiento del ataque agudo de la CPH fue semejante al empleado en los casos de porfiria aguda intermitente o PV carbohidratos (ataques agudos 300- 500 g/diarios, ataques leves 20 - 40 g/diarios) complejo vitamínico B y ácido fólico (30 mg/día). Cuando los pacientes presentaron signos clínicos cutáneos se administró S-adenosil-L-metionina 12 mg/kg/día durante 3 semanas.

Heme biosynthesis pathway regulation in a model of hepatocarcinogenesis pre-initiation.

1. Heme regulation before the appearance of hyperplastic nodules was investigated in mice models of hepatocarcinogenesis. 2. With this aim 5-aminolaevulinate synthetase (ALA-S), microsomal heme-oxygenase (MHO), mitochondrial and cytoplasmic rhodanese activities were examined throughout a period of 35 days in animals exposed to dietary p-dimethylaminoazobenzene (DAB). 3. ALA-S activity was significantly diminished (50%) on day 14, then showing a sharply rising profile from day 28 onwards, and reaching 350% on day 35. 4. A similar profile was observed for mitochondrial rhodanese activity. 5. Changes in MHO and cytoplasmic rhodanese activities were almost the opposite to those observed for ALA-S. 6. The distinctive alteration in mitochondrial and cytoplasmic rhodanese would suggest that it plays a subtle role in ALA-S regulation during carcinogenesis initiation through a mechanism that appears to involve subcellular localization controls perhaps by means of the breakage of cystine trisulphide postulated to act as an ALA-S activator. 7. Taking into account the present results, we suggest a probable mechanism for the onset of hepatocarcinogenesis that includes a primary activating liver status, provoking biochemical aberration leading to the stage of initiation of hepatocarcinogenesis involving the whole organ.

Heme biosynthesis in human breast cancer--mimetic "in vitro" studies and some heme enzymic activity levels.

1. Porphyrin biosynthesis from delta-aminolevulinic acid (ALA) was investigated using the technique of tissue explant cultures, in both human breast cancer and its original normal tissue. 2. The activity of ALA-dehydratase, porphobilinogenase and uroporphyrinogen decarboxylase was directly determined in both tumor and normal mammary tissues. 3. Porphyrin synthesis capacity of human breast carcinoma was 20-fold enhanced, as compared with normal tissue, at least between the stages of porphobilinogen and coproporphyrinogen formation. 4. The activity of the three enzymes examined was always lower in normal tissue than in tumoral tissue. 5. Present findings show that porphyrin biosynthesis is increased in breast cancer tissue.

Two cases of infantile porphyria cutanea tarda: successful treatment with oral S-adenosyl-L-methionine and low-dose oral chloroquine.

In a 7-year-old girl and a 12-year-old boy, with photosensitivity and hypertrichosis, the diagnosis of familial porphyria cutanea tarda was confirmed by the characteristic pattern of urinary porphyrin excretion, diminished erythrocyte uroporphyrinogen decarboxylase and elevated plasma porphyrin index with emission maxima at 617-618 nm. The patients were treated with a combination of low-dose oral chloroquine and oral S-adenosyl-L-methionine (SAM); in one case alkalinization of urine was also applied. Complete clinical and biochemical recovery was achieved within 3 months. No adverse ophthalmological or other side-effects were observed. We propose that the treatment of choice should be oral SAM (12 mg/kg/day) for 3 weeks and oral chloroquine (2 X 100 mg weekly) for about 120-150 days or until improvement of clinical and biochemical abnormalities is attained. So far no relapses have occurred. This combined therapy appears to be safe, simple, effective and very convenient for both patients and physicians.

[Bacteriochlorophyll a synthesis in Rhodopseudomonas palustris]. / Biosíntesis de bacterioclorofila a en Rhodopseudomonas palustris.

By means of electron microscope it was demonstrated that photosynthetically-grown Rhodopseudomonas palustris exhibits an intracytoplasmic membrane system (Figure 1a), which is not observed in aerobically-dark grown bacteria (Figure 1b). The content of bacteriochlorophyll alpha and the enzyme activity of succinil-CoA-synthetase, ALA-sinthetase and ALA-dehydratase in several media grown Rhodopseudomonas palustris could be measured. Aerobically-dark grown cells do not synthetize bacteriochlorophyll alpha and the activity of ALA-synthetase is lower than in photosynthetically-grown cells (Table 1), suggesting a possible regulatory role for this enzyme in the pigment biosynthesis. Some inhibitors of electron transport and uncouplers of photophosphorylation inhibit both the bacterial growth and bacteriochlorophyll alpha biosynthesis (Table 2), while the levels of ALA-synthetase are not affected. If the incubation in the presence of these kinds of compounds is prolongated, the effects disappear. Although the regulatory role of ALA-synthetase should be very important, apparently it would not be the unique regulatory factor for bacteriochlorophyll alpha biosynthesis in Rhodopseudomonas palustris.

Biosíntesis de bacterioclorofila a en Rhodopseudomonas palustris. / [Bacteriochlorophyll a synthesis in Rhodopseudomonas palustris]

By means of electron microscope it was demonstrated that photosynthetically-grown Rhodopseudomonas palustris exhibits an intracytoplasmic membrane system (Figure 1a), which is not observed in aerobically-dark grown bacteria (Figure 1b). The content of bacteriochlorophyll alpha and the enzyme activity of succinil-CoA-synthetase, ALA-sinthetase and ALA-dehydratase in several media grown Rhodopseudomonas palustris could be measured. Aerobically-dark grown cells do not synthetize bacteriochlorophyll alpha and the activity of ALA-synthetase is lower than in photosynthetically-grown cells (Table 1), suggesting a possible regulatory role for this enzyme in the pigment biosynthesis. Some inhibitors of electron transport and uncouplers of photophosphorylation inhibit both the bacterial growth and bacteriochlorophyll alpha biosynthesis (Table 2), while the levels of ALA-synthetase are not affected. If the incubation in the presence of these kinds of compounds is prolongated, the effects disappear. Although the regulatory role of ALA-synthetase should be very important, apparently it would not be the unique regulatory factor for bacteriochlorophyll alpha biosynthesis in Rhodopseudomonas palustris.

Biosíntesis de bacterioclorofila a en Rhodopseudomonas palustris / [Bacteriochlorophyll a synthesis in Rhodopseudomonas palustris]

By means of electron microscope it was demonstrated that photosynthetically-grown Rhodopseudomonas palustris exhibits an intracytoplasmic membrane system (Figure 1a), which is not observed in aerobically-dark grown bacteria (Figure 1b). The content of bacteriochlorophyll alpha and the enzyme activity of succinil-CoA-synthetase, ALA-sinthetase and ALA-dehydratase in several media grown Rhodopseudomonas palustris could be measured. Aerobically-dark grown cells do not synthetize bacteriochlorophyll alpha and the activity of ALA-synthetase is lower than in photosynthetically-grown cells (Table 1), suggesting a possible regulatory role for this enzyme in the pigment biosynthesis. Some inhibitors of electron transport and uncouplers of photophosphorylation inhibit both the bacterial growth and bacteriochlorophyll alpha biosynthesis (Table 2), while the levels of ALA-synthetase are not affected. If the incubation in the presence of these kinds of compounds is prolongated, the effects disappear. Although the regulatory role of ALA-synthetase should be very important, apparently it would not be the unique regulatory factor for bacteriochlorophyll alpha biosynthesis in Rhodopseudomonas palustris.

Studies on the porphobilinogen deaminase-uroporphyrinogen cosynthetase system of cultured soya-bean cells.

1. Porphobilinogenase was isolated and purified from soya-bean callus tissue; its components, porphobilinogen deaminase and uroporphyrinogen isomerase, were separated and purified. 2. The purified porphobilinogenase was resolved into two bands on starch-gel electrophoresis. The molecular weights of porphobilinogenase, deaminase and isomerase fractions were determined by the gel-filtration method. Porphobilinogenase activity was affected by the presence of air; uroporphyrinogens were only formed under anaerobic conditions, although substrate consumption was the same in the absence of oxygen as in its presence. 3. pH-dependence of both porphobilinogenase and deaminase was the same and a sharp optimum at pH 7.2 was obtained. Isomerase was heat-labile, but the presence of ammonium ions or porphobilinogen afforded some protection against inactivation. The action of several compounds added to the system was studied. Cysteine, thioglycollate, ammonium ions and hydroxylamine inhibited porphobilinogenase; certain concentrations of sodium and magnesium salts enhanced activity; some dicarboxylic acids and 2-methoxy-5-nitrotropone inhibited the deaminase. 4. delta-Aminolaevulate and ethionine in the culture media stimulated porphyrin synthesis and increased porphobilinogenase activity, whereas iron deficiency resulted in porphyrin accumulation. 5. The development of chlorophyll and porphobilinogenase on illumination of dark-grown callus was followed. 6. A hypothetical scheme is suggested for the enzymic synthesis of uroporphyrinogens from porphobilinogen.