Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities in blood of six enzymes of the haem biosynthetic pathway have been determined in 12 patients with rheumatoid disease, six of whom were anaemic. The porphyrin and porphyrin-precursor intermediary products of haem biosynthesis were also determined in blood, urine and faeces. No significant differences were found between anaemic and non-anaemic subjects. Failure of delta-amino-laevulinate synthase activity to increase in response to anaemia may be the nature of the marrow unresponsiveness suggested as one factor in the causation of the anaemia. Normal ferrochelatase activity and normal concentrations of free protoporphyrin support the view that iron is effectively unavailable although present in normal amounts. Coproporphyrinogen oxidase activity was significantly depressed.
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PMID:Haem biosynthesis in rheumatoid disease. 72 73

Anemia is a constant complication of uremia. As it has been suggested that uremic toxins (middle molecules) play an important role in the mechanism of anemia, we studied the activities of three heme-synthesizing enzymes: delta-aminolevulinic acid dehydratase, porphobilinogen deaminase and ferrochelatase. In 26 patients on regular dialysis therapy, all three enzymes had significantly lower values than in normal control subjects. From our results, it can be assumed that the decreased heme biosynthesis in chronic uremic patients might be caused by a lack of erythropoietin or by uremic toxins inhibiting erythropoietin and/or heme-synthesizing enzymes.
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PMID:Heme synthesis in anemia of the uremic state. 75 May 46

In order to investigate, whether heme would induce a response in myelodysplastic syndromes (MDS), 14 symptomatic patients (4 RA, 3 RARS and 7 RAEB) were treated with infusions of heme arginate 3 mg/kg body weight on 4 consecutive days, mostly for six cycles at 2-week intervals. Three of 14 patients (21%) showed an improvement in anemia (97-152, 79-120 and 92-114 g/l) within a few weeks, and 1 showed a milder increase in hemoglobin level (102-118 g/l). Of the 2 responders with marked thrombocytopenia, 1 showed an improvement in the platelet count (7-37 x 10(9)/l) and her regular need for red cell and platelet transfusions ceased. Some regression in bone marrow (BM) cytology was seen in all 3 responders. One of the responders is still in remission 41 months after cessation of the treatment, while in the other 2 the response lasted for 26 and 5 months. Four patients progressed during the treatment: 1 RA to RAEB, 1 RAEB to RAEBt and 2 RAEB, both with very complex chromosomal abnormalities at the beginning of the therapy, to acute erythroleukemia (AML-M6). Pretreatment delta-aminolevulinic acid synthase and heme synthase activities were generally low. Five patients had mild thrombophlebitis, but not after the infusion procedure was changed. No other side-effects common to growth factors occurred. In conclusion, it is likely that heme arginate has a therapeutic effect on some MDS patients, obviously by stimulating erythropoiesis. The response may be long-lasting.
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PMID:Therapeutic effect of heme arginate in myelodysplastic syndromes. 834 47

Toxic effect of lead is related, among others, to metabolic interactions with essential trace elements i.e. iron, zinc and copper. Lead stimulates urinary excretion of these elements interfering with their reabsorption in kidney as well as inhibits ceruloplasmin activity in plasma, ferrochelatase activity in reticulocytes and copper- and zinc-dependent superoxide dismutase activity in tissues--with all functional consequences for organism. Iron, zinc and copper deficiency results in increased lead toxicity through considerable enhancement of lead absorption from intestinal tract, producing greater degree of anemia as well as decreasing of metalloenzymes activity. Increasing dietary zinc and probably copper suppresses intestinal absorption of lead. The addition of iron, zinc and copper to the diet prevents lead accumulation within the tissues and subsequent toxicity of this element. It seems that increasing intake of food products containing a lot of essential trace elements can diminish risk of lead toxicity for human.
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PMID:[Effects of harmful trace elements on iron, zinc and copper: their interactions in animals and humans. II. Lead]. 180 38

A viable autosomal recessive mutation (named fch, or ferrochelatase deficiency) causing jaundice and anemia in mice arose in a mutagenesis experiment using ethylnitrosourea. Homozygotes (fch/fch) display a hemolytic anemia, photosensitivity, cholestasis, and severe hepatic dysfunction. Protoporphyrin is found at high concentration in erythrocytes, serum, and liver. Ferrochelatase activity in various tissues is 2.7-6.3% of normal. Heterozygotes (+/fch) are not anemic and have normal liver function; they are not sensitive to light exposure; ferrochelatase activity is 45-65% of normal. Southern blot analysis using a ferrochelatase cDNA probe reveals no gross deletion of the ferrochelatase gene. This is the first spontaneous form of erythropoietic protoporphyria in the house mouse. Despite the presence in the mouse of clinical and biochemical features infrequent in the human, this mutation may represent a model for the human disease, especially in its severe form.
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PMID:Erythropoietic protoporphyria in the house mouse. A recessive inherited ferrochelatase deficiency with anemia, photosensitivity, and liver disease. 193 58

The effects of chronic ethylene oxide (EtO) inhalation on porphyrin-heme metabolism were investigated. When Wistar male rats were exposed to 500 ppm EtO for 6 h a day, 3 times a week for 13 weeks, hemoglobin content significantly decreased, and a normocytic and normochromic anemia was found. In the liver, cytochrome P-450 and protoheme significantly decreased but wet weight, microsomal protein and cytochrome b5 were not affected. The activity of delta-aminolevulinic acid (ALA) synthase increased while ALA dehydratase did not change. The activity of hepatic ferrochelatase decreased time-dependently. Uroporphyrin increased 37% and coproporphyrin tended to increase in the liver. The concentration of protoporphyrin in the liver and erythrocytes tended to increase. Coproporphyrin excretion in the urine showed a 5-6-fold increase while there was no significant increase in urinary ALA excretion. These results indicate that chronic inhalation of EtO causes alterations of hepatic porphyrin-heme metabolism as well as anemia and may affect mechanisms of adaptation to xenobiotics.
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PMID:Chronic inhalation effects of ethylene oxide on porphyrin-heme metabolism. 231 47

The character and pathogenesis of hemoglobin deficit (gene symbol, hbd), an autosomal recessive trait in the mouse, were studied. The main hematological features of hemoglobin deficit are anemia, red cell hypochromia and microcytosis, and reticulocytosis. The absence of raised fecal urobilinogen excretion and frank hyperbilirubinemia and bilirubinuria suggests that excess hemolysis is not the primary cause of the anemia. The raised plasma iron concentration and the failure of the anemia to respond to parenteral iron treatment indicate that the anemia is not due to iron deficiency. The absence of siderocytes and sideroblasts suggests that anemia is probably not due to ferrochelatase deficiency. Thalassemia is excluded by the finding of balanced reticulocyte globin chain synthesis. The markedly elevated levels of free red cell protoporphyrin taken together with the other findings already noted suggest that the anemia of hemoglobin deficit is due to a defect in the erythroid cell iron procurement mechanisms leading in turn to diminished heme and hemoglobin synthesis.
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PMID:Hemoglobin deficit: an inherited hypochromic anemia in the mouse. 396 Aug 59

The nature of anemia formation in lead poisoning is still unknown, especially of its mechanism. Rimington proposed a hypothesis that lead interferes with a specific enzyme (ferrochelatase) system, which is responsible for incorporating iron into the protoporphyrin IX molecules to form heme. In the present study, heme synthesis in mitochondria (Mt) of liver and bone marrow, and 59Fe behavior in vivo were investigated in rabbits to verify his hypothesis. The experimental five groups were as follows: 1) lead (Pb) poisoning by administration of 10-20 mg Pb/kg at a time, subcutaneously injected 10 times in all during 30 days, 2) phenylhydrazine (PH) poisoning, 10 mg PH/kg, 3 times subcutaneously during 3 days, 3) bleeding of about 105 ml of blood in total by venesection through 7 times treatments, 4) low feeding, synthetic feeding pellets of 30 g/d/cap. or 70 g/d/cap. 5) control, by administration of 5% glucose instead of lead injection with 120 g/d/cap. of the feeding pellets, with drinking water 300 ml/d/cap. for 30 days. 59Fe-plasma was prepared by the following procedure: 5 ml of plasma from each rabbit having been incubated with 5 microCi of 59Fe citrate at 37 degrees C for 30 minutes, 59Fe-plasma was purified partially by Borova's method. The prepared 59Fe-plasma was injected intravenously into the rabbits in each group. Urinary coproporphrin (CP-U), erythrocyte protoporphyrin (FFP), Hb, Ht, MCHC, reticulocyte (Rt), and protoheme formed by Mt, were determined to examine the relationship between lead and porphyrinheme metabolism. 59Fe behavior was estimated by detecting the plasma iron disappearance rate (half life time of 59Fe in plasma), 59Fe intake into erythrocytes, and the retention of 59Fe in tissues. Increase of FEP in lead poisoning was not caused by hemolysis, because FEP did not increase in PH group (Table 1). CP-U slightly increased in PH group, but not in the bleeding group (Table 2). This increase of CP-U must be due to acceleration of hematopoiesis in PH poisoning, because PH and bleeding groups showed an increase of Rt, counting 222.2 and 85.3%, respectively, at the termination of the treatment, while the Pb group did not show any obvious reticulocytosis (Table 3). PH, bleeding, and Pb(10 mg/kg) groups showed shorter half life time of 59Fe in plasma, while the 30 g/d-feeding group showed longer time (Table 8). During 100 minutes after 59Fe injection, incorporation of 59Fe into erythrocytes was higher in PH and bleeding groups than those in other treatment groups and the control (Table 9).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Heme synthesis and iron turnover in rabbits with experimental lead poisoning]. 665 84

The effects of acute ethanol ingestion on the activities of the enzymes of haem biosynthesis in peripheral blood cells have been monitored in eight healthy subjects. The mitochondrial enzymes delta-aminolaevulinic acid (ALA) synthase, coproporphyrinogen oxidase and ferrochelatase were measured in leucocytes and the cytosolic enzymes ALA dehydratase, porphobilinogen (PBG) deaminase and uroporphyrinogen decarboxylase in erythrocytes. Ingestion of 1 . 316 mol ethanol resulted in increased activity of the rate-controlling enzymes ALA synthase and PBG deaminase and decreased activity of the other four enzymes. There was also increased urinary excretion of coproporphyrin. These observations may be relevant to the biochemical mechanisms involved in the ethanol-related conditions, sideroblastic anaemia, cutaneous hepatic porphyria and hepatic siderosis.
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PMID:Acute ethanol ingestion and haem biosynthesis in healthy subjects. 678 Mar 56

The activities of six of the enzymes of haem biosynthesis have been examined in eleven chronic alcoholics admitted to hospital for alcohol withdrawal. The mitochondrial enzymes delta-aminolaevulinic acid (ALA) synthase, coproporphyrinogen oxidase and ferrochelatase were monitored in peripheral leucocytes and the cytosolic enzymes ALA dehydratase, uroporphyrinogen-1-synthase and uroporphyrinogen decarboxylase in peripheral erythrocytes. Compared with control subjects the activity of the initial and rate controlling enzyme of the pathway, ALA synthase, was increased (P less than 0.01) and the activities of ALA dehydratase and uroporphyrinogen decarboxylase depressed (P less than 0.01, P less than 0.02 respectively) on the day after admission but all returned to normal by the tenth to twentieth days after alcohol withdrawal. This stimulation of ALA synthase and inhibition of uroporphyrinogen decarboxylase explains the mechanism by which chronic alcohol ingestion may precipitate cutaneous hepatic porphyria. Two of the alcoholics were anaemic without evidence of haematinic deficiency and this was associated with depressed ferrochelatase activity and iron and porphyrin accumulation. The anaemia and related biochemical abnormalities in these two subjects were all corrected with alcohol withdrawal. It is proposed that inhibition of ferrochelatase activity is the biochemical basis of alcohol related sideroblastic anaemia.
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PMID:Abnormal haem biosynthesis in chronic alcoholics. 680 Aug 21


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