Alterations in the Activity of Enzymes of Haem Biosynthesis in Lead Poisoning and Acute Hepatic Porphyria

1977 ◽  
Vol 53 (4) ◽  
pp. 335-340
Author(s):  
B. C. Campbell ◽  
M. J. Brodie ◽  
G. G. Thompson ◽  
P. A. Meredith ◽  
M. R. Moore ◽  
...  
Keyword(s):  
Lead Poisoning ◽  
Haemoglobin Concentration ◽  
Acute Intermittent Porphyria ◽  
Normal Subjects ◽  
Uroporphyrinogen Decarboxylase ◽  
Coproporphyrinogen Oxidase ◽  
Hereditary Coproporphyria ◽  
Haem Biosynthesis ◽  
Significant Depression ◽  
Activity Of Enzymes

1. The activities of six of the enzymes of haem biosynthesis have been assayed in peripheral blood from patients with lead poisoning, acute intermittent porphyria or hereditary coproporphyria. 2. Compared with normal subjects the lead-poisoned subjects had highly significant depression of δ-aminolaevulinate dehydratase, coproporphyrinogen oxidase and ferrochelatase. 3. Lead-poisoned subjects had highly significant elevation of δ-aminolaevulinate synthase activity. 4. δ-Aminolaevulinate synthase activity was inversely related to the haemoglobin concentration. 5. Increased δ-aminolaevulinate synthase and decreased δ-aminolaevulinate dehydratase activity are also found in acute intermittent porphyria. 6. Increased δ-aminolaevulinate synthase, normal porphobilinogen deaminase and uroporphyrinogen decarboxylase and decreased coproporphyrinogen oxidase are found in both lead poisoning and hereditary Coproporphyria. 7. These enzyme changes explain the recognized patterns of porphyrins and porphyrin precursors in blood and urine in these conditions.

The Treatment of Acute Intermittent Porphyria with Laevulose

1977 ◽  
Vol 53 (4) ◽  
pp. 365-371 ◽  
Author(s):  
M. J. Brodie ◽  
M. R. Moore ◽  
G. G. Thompson ◽  
A. Goldberg
Keyword(s):  
Acute Intermittent Porphyria ◽  
Acute Attack ◽  
Therapeutic Regimen ◽  
Porphobilinogen Deaminase ◽  
Mitochondrial Enzymes ◽  
Uroporphyrinogen Decarboxylase ◽  
Coproporphyrinogen Oxidase ◽  
Marked Diminution ◽  
Haem Biosynthesis ◽  
Cytosolic Enzymes

1. The activities of the enzymes of haem biosynthesis were studied in 23 patients with acute intermittent porphyria. The mitochondrial enzymes δ-aminolaevulinate synthase, coproporphyrinogen oxidase and ferrochelatase were measured in leucocytes and the cytosolic enzymes δ-aminolaevulinate dehydratase, porphobilinogen deaminase and uroporphyrinogen decarboxylase in erythrocytes. 2. Leucocyte δ-aminolaevulinate synthase activity was elevated (P < 0·001), with marked diminution of porphobilinogen deaminase activity (P < 0·001) and reduction in the activities of δ-aminolaevulinate dehydratase (P < 0·01) and uroporphyrinogen decarboxylase (P < 0·005). 3. A therapeutic regimen based on intravenous laevulose infusion was studied. In four patients in acute attack and one in remission laevulose treatment was associated with a fall in δ-aminolaevulinate synthase activity, a rise in porphobilinogen deaminase and uroporphyrinogen decarboxylase activities, and a fall in urinary porphyrin precursor excretion (P < 0·001). These studies provide a basis for the evaluation of the use of sugars in acute intermittent porphyria.

Amounts of Faecal Porphyrin-Peptide Conjugates in the Porphyrias

1972 ◽  
Vol 43 (2) ◽  
pp. 299-302 ◽  
Author(s):  
M. R. Moore ◽  
G. G. Thompson ◽  
A. Goldberg
Keyword(s):  
Porphyria Cutanea Tarda ◽  
Acute Intermittent Porphyria ◽  
Normal Subjects ◽  
Erythropoietic Protoporphyria ◽  
Peptide Conjugates ◽  
Peptide Complex ◽  
Variegate Porphyria ◽  
Hereditary Coproporphyria ◽  
Different Types

1. The levels of ‘X-porphyrin’, a porphyrin-peptide complex, have been studied in the faeces of patients with different types of porphyria, as well as in fifty normal subjects. 2. These levels have been shown to be significantly elevated in untreated porphyria cutanea tarda and in variegate porphyria. 3. Lesser elevations were seen in acute intermittent porphyria and hereditary coproporphyria. There was no elevation in erythropoietic protoporphyria.

scholarly journals Renal Mechanism for Excretion of Porphyrin Precursors in Patients with Acute Intermittent Porphyria and Chronic Lead Poisoning

Blood ◽  
1965 ◽  
Vol 26 (2) ◽  
pp. 181-189 ◽  
Author(s):  
ROBERT DRUYAN ◽  
BIRGITTA HAEGER-ARONSEN ◽  
WILFRIED VON STUDNITZ ◽  
JAN WALDENSTRÖM
Keyword(s):  
Lead Poisoning ◽  
Acute Intermittent Porphyria ◽  
Normal Subjects ◽  
Tubular Reabsorption ◽  
The Other ◽  
Lead Intoxication ◽  
Serum Concentrations ◽  
Lead Workers ◽  
Chronic Lead Intoxication

Abstract Serum concentrations of ALA and PBG have been measured in normal subjects, patients with AIP, and lead workers. Both porphyrin precursors are significantly increased in serum from porphyric patients, and serum ALA is elevated in lead workers. Endogenous clearance measurements, when compared with creatinine clearances, are consistent with significant tubular reabsorption of ALA and PBG under physiologic circumstances, and with an "overflow" mechanism for increased excretion in AIP or lead intoxication. Three of 8 porphyric patients showed an aminoaciduria; tyrosine was involved in 2, tryptophan in the other 3. Evidence to suggest a specific renal defect contributing to increased ALA excretion in chronic lead intoxication was not obtained.

Alterations in Haem Biosynthesis during the Human Menstrual Cycle: Studies in Normal Subjects and Patients with Latent and Active Acute Intermittent Porphyria

1982 ◽  
Vol 62 (2) ◽  
pp. 183-191 ◽  
Author(s):  
K. E. L. McColl ◽  
A. M. Wallace ◽  
M. R. Moore ◽  
G. G. Thompson ◽  
A. Goldberg
Keyword(s):  
Enzyme Activity ◽  
Menstrual Cycle ◽  
Urinary Excretion ◽  
Plasma Concentrations ◽  
Acute Intermittent Porphyria ◽  
Normal Subjects ◽  
Normal Female ◽  
Haem Biosynthesis ◽  
Human Menstrual Cycle ◽  
Female Subjects

1. The timing of onset of attacks of acute intermittent porphyria (AIP) in relation to the menstrual cycle has been studied in three patients experiencing frequent attacks. Nineteen of their 27 admissions in attack for which no exogenous precipitating causes could be identified were during the 7 days before the onset of menstruation. 2. Haem biosynthesis has been monitored throughout a complete menstrual cycle in six normal females and compared with that in male control subjects. In the females, there was marked fluctuation in the activity of the rate-controlling enzyme of haem biosynthesis, δ-aminolaevulinate (ALA) synthase, which was monitored in peripheral leucocytes. The fluctuation did not show any clear association with menstruation and no association was found between the enzyme activity and ovarian or adrenal steroid production as monitored by measurement of plasma concentrations of androstenedione, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS), testosterone, oestradiol and progesterone. The activity of uroporphyrinogen I (URO) synthase, the enzyme which is deficient in AIP, was monitored in peripheral erythrocytes of four of the normal female subjects and was similar to that found in four male control subjects. The urinary excretion of ALA and porphobilinogen (PBG) was also similar in the male and female subjects and there was no association with the phase of the menstrual cycle or activity of the enzymes studied. 3. Studies of haem biosynthesis have been made throughout a complete menstrual cycle in a 26 year old female with latent AIP. The activity of leucocyte ALA synthase showed more marked fluctuation than in the normal female subjects and was highest at the time of menstruation. No association was apparent between the activity of ALA synthase and plasma concentrations of androstenedione, DHA and DHAS. The fluctuation in activity of erthrocyte URO synthase was similar to that of the normal subjects. The urinary excretion of ALA and PBG was normal throughout and showed no correlation with fluctuations in enzyme activity. 4. The human menstrual cycle modifies haem biosynthesis in normal subjects as well as in subjects with latent and manifested AIP. 5. The human female menstrual cycle modifies haem biosynthesis in peripheral blood cells as well as in the liver.

Red Cell Glutathione in Anaemia

1973 ◽  
Vol 18 (6) ◽  
pp. 177-181 ◽  
Author(s):  
J. Hopkins ◽  
G. R. Tudhope
Keyword(s):  
Inverse Relationship ◽  
Reduced Glutathione ◽  
Haemoglobin Concentration ◽  
Normal Subjects ◽  
Initial Therapy ◽  
Megaloblastic Anaemia ◽  
Red Cells ◽  
Red Cell ◽  
A Value ◽  
Normal Mean

Erythrocyte reduced glutathione (GSH) has been measured in 17 normal subjects and in 70 patients with anaemia of various causes; the red cells of most of the anaemic patients contained abnormally high levels of GSH. In the group of cases of untreated megaloblastic anaemia in which the haemoglobin concentration was less than 8.0 g. per 100 ml., there was an inverse relationship between the erythrocyte GSH level and the haemoglobin concentration. During initial therapy in megaloblastic anaemia, as the haemoglobin concentration increased, the GSH level decreased towards normal; the time taken for the GSH level to reach a value 2 standard deviations above the normal mean was inversely related to the initial haemoglobin concentration. In the red cells of patients with anaemia there was no correlation between the GSH level and the activity of glutathione peroxidase. The significance of these findings is discussed.

Effects of Hexachlorobenzene Feeding and Iron Overload on Enzymes of Haem Biosynthesis and Cytochrome P450 in Rat Liver

1977 ◽  
Vol 53 (2) ◽  
pp. 111-115 ◽  
Author(s):  
M. Louw ◽  
A. C. Neethling ◽  
V. A. Percy ◽  
M. Carstens ◽  
B. C. Shanley
Keyword(s):  
Cytochrome P450 ◽  
Synergistic Effect ◽  
Progressive Increase ◽  
Decarboxylase Activity ◽  
Progressive Decrease ◽  
Uroporphyrinogen Decarboxylase ◽  
Time Intervals ◽  
Liver Cytochrome ◽  
Haem Biosynthesis ◽  
P450 Concentration

1. The effect of hexachlorobenzene feeding on liver δ-aminolaevulinate synthase, uroporphyrinogen decarboxylase and cytochrome P450 was studied at various time-intervals in siderotic and non-siderotic rats. 2. In the non-siderotic group hexachlorobenzene feeding led to a progressive decrease in liver uroporphyrinogen decarboxylase activity, accompanied by a progressive increase in δ-aminolaevulinate synthase activity. Cytochrome P450 concentrations were above normal throughout but fell toward the end of the experiment. 3. Similar but more marked changes were found in the siderotic animals. The fall in uroporphyrinogen decarboxylase activity occurred earlier and was significantly greater in these animals, whereas the increase in δ-aminolaevulinate synthase activity was consistently larger. Liver cytochrome P450 concentration also rose but to a lesser extent than that in the non-siderotic rats. 4. Hexachlorobenzene-induced porphyria would seem to be attributable to inhibition or inactivation of hepatic uroporphyrinogen decarboxylase. Hepatic siderosis has a synergistic effect with hexachlorobenzene on this enzyme and may exert additional effects by promoting cytochrome P450 turnover.

scholarly journals Correlation between plasma 5-aminolevulinic acid concentrations and indicators of oxidative stress in lead-exposed workers

1997 ◽  
Vol 43 (7) ◽  
pp. 1196-1202 ◽  
Author(s):  
Cristine A Costa ◽  
Gilmar C Trivelato ◽  
Adriana M P Pinto ◽  
Etelvino J H Bechara
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Lead Poisoning ◽  
Stress Responses ◽  
Aminolevulinic Acid ◽  
Aerobic Oxidation ◽  
Protoporphyrin Ix ◽  
Acute Intermittent Porphyria ◽  
Blood Concentrations ◽  
Exposed Workers

Abstract 5-Aminolevulinic acid (ALA), a heme precursor accumulated in acute intermittent porphyria and lead poisoning, undergoes metal-catalyzed aerobic oxidation at physiological pH to yield reactive free radical species (O2−·&gt;, HO·, and ALA·). We analyzed the relationships between plasma ALA concentrations, blood concentrations of lead, protoporphyrin IX (PP-IX), superoxide dismutase (SOD), and methemoglobin (metHb), and urine chemiluminescence (CL) in samples collected from lead-exposed workers. All variables measured were substantially (P &lt;0.01) higher (2–8-fold) in the lead-exposed workers (n = 60). Plasma ALA concentrations were, on average, 6-fold higher in lead-exposed workers. We observed positive linear relationships between ALA and lead (r = 0.992), ALA and PP-IX (r = 0.891), ALA and metHb (r = 0.984), lead and SOD (r = 0.948), ALA and urine CL (r = 0.987), and lead and PP-IX (r = 0.993). These data are consistent with our free radical hypothesis for lead poisoning, where ALA distribution to and accumulation in several organs may trigger oxidative stress responses.

scholarly journals Rapid Quantitative Method Using Spin Columns to Measure Porphobilinogen in Urine

2008 ◽  
Vol 54 (2) ◽  
pp. 429-431 ◽  
Author(s):  
Mikhail Roshal ◽  
Jeanne Turgeon ◽  
Petrie M Rainey
Keyword(s):  
Quantitative Method ◽  
Quantitative Methods ◽  
Exchange Resin ◽  
Anion Exchange Resin ◽  
Acute Intermittent Porphyria ◽  
Acute Porphyria ◽  
Spin Column ◽  
Deming Regression ◽  
Hereditary Coproporphyria ◽  
Urine Specimens

Abstract Background: Large increases of urinary porphobilinogen (PBG) indicate acute porphyria, which may be due to acute intermittent porphyria, variegate porphyria, or hereditary coproporphyria. These conditions are relatively rare but share symptoms with more common conditions, such as acute surgical abdomen, and often must be ruled out rapidly. Reported quantitative methods for PBG measurement are time-consuming and inconvenient. We developed a rapid quantitative method that uses resin-packed spin columns to measure PBG in urine. Method: We applied urine to anion exchange resin in a spin column, then performed centrifugal separation and washing. PBG was eluted in 1 mol/L acetic acid and reacted with Ehrlich’s reagent. After 5 min, we measured absorbance at 525, 555, and 585 nm. PBG concentration (mg/L) was calculated as 88 (A555 − ½(A525 + A585)). Results: The reportable PBG concentration range was 0.2–15 mg/L. Between-day (total) imprecision (CV) was 8.4% at 1.2 mg/L and 3.5% at 4.4 mg/L. Comparison with our established method (x) yielded a Deming regression equation: y = 1.04x − 0.01 mg/L (R2 = 0.98; Sy,x = 0.87 mg/L). No interference was noted from urobilinogen or highly colored urine specimens. Conclusions: This method for PBG measurement is more rapid and precise than other methods. This test can serve as a quick screening test and facilitates batch analysis for routine quantitative testing.

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