Lead poisoning: association with hemolytic anemia, basophilic stippling, erythrocyte pyrimidine 5'-nucleotidase deficiency, and intraerythrocytic accumulation of pyrimidines.

Valentine, William N.; Paglia, Donald E.; Fink, Kay; Madokoro, Glenn

doi:10.1172/jci108545

Cited by 106 publications

(40 citation statements)

References 30 publications

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“…The energy charge is also normal in two children with P5ND 111) . The observed pattern of glycolytic intermediates in lead poisoning also suggestes that the activity of the Embden-Meyerhof pathway is normal 113,114) . However, Torrance and Whittaker 109) have found that the concentrations of ADP and AMP in red blood cells of P5ND are between 2 and 3 times of normal, and the distribution of adenine nucleotides is abnormal with the lower energy forms being favored.…”

Section: ) Accumulation Of Pyrimidine Nucleotides In Erythrocytesmentioning

confidence: 64%

Biomarkers of Lead Exposure.

2000

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Biomarkers of exposure, effect, and susceptibility are reviewed in relation to lead exposure. Of the biomarkers of lead exposure, blood lead (Pb-B), mainly red cell lead, is a representative of soft tissue lead, and most widely used as measures of body burden and absorbed (internal) doses of lead. Urine lead (Pb-U) as well as plasma lead (Pb-P) increases exponentially with increasing Pb-B under a steady-state situation and is a reflection of recent exposure. The amount of lead in plasma and urine (MPb-P and MPb-U) after administration of a chelating agent (e.g CaEDTA) can be useful for biomarkers of internal exposure of lead, reflecting the mobilizable pool of lead which consists of mainly blood and soft tissue lead with only a small fraction derived from bones. The critical effects in bone marrow arise mainly from the interaction of lead with some enzymatic process responsible for heme synthesis. The effects can be used for the biomarkers of effects. They are the inhibition of delta-aminolevulinic acid dehydratase (ALAD) and the variation in some metabolite concentrations (e.g. delta-aminolevulinic acid in urine (ALA-U), blood (ALA-B) or plasma (ALA-P), coproporphyrin in urine (CP), zinc protoporphyrin (ZP) in blood). The activities of pyrimidine nucleotidase (P5'N) and nicotinamide adenine dinucleotide synthetase (NADS) in blood are also decreased in lead exposure, and nucleotide contents in blood is altered in lead exposure. These effects of lead on human can be also useful biomarkers of effect. The differences in levels of heme precursors between two types of ALAD genotypes might be attributable to those in the affinity of different ALAD isozymes to lead. ALAD1 homozygotes have higher levels of ZP and ALA in comparison with ALAD2 carriers at the high lead exposure, suggesting that ALAD1 homozygotes might be more susceptible for disturbance in heme biosynthesis by lead than ALAD2 carriers.

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Section: ) Accumulation Of Pyrimidine Nucleotides In Erythrocytesmentioning

confidence: 64%

Biomarkers of Lead Exposure.

2000

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“…A lead-induced deficiency of P5N-I also results in the induction of basophilic stippling and premature erythrocyte hemolysis analogous to that encountered in genetically induced enzyme-deficiency syndrome [17,18,22]. Treatment of erythrocytes with lead also inhibits canine P5N-I [8], resulting in retardation of the morphological reticulocyte maturation [7].…”

Section: Discussionmentioning

confidence: 96%

Inhibitory Effect of Pyrimidine and Purine Nucleotides on the Multiplication of <i>Babesia gibsoni</i>: Possible Cause of Low Parasitemia and Simultaneous Reticulocytosis in Canine Babesiosis

Hossain

Yamato

Yamasaki

et al. 2004

The Journal of Veterinary Medical Science

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ABSTRACT. The present study was conducted to determine the cause of low parasitemia and simultaneous reticulocytosis in canine babesiosis. The parasitemia was significantly decreased in in vitro cultures of Babesia gibsoni by the pretreatment of host canine erythrocytes with lead acetate, which is a specific inhibitor of pyrimidine 5'-nucleotidase subclass I (P5N-I). The serum from dogs chronically infected with B. gibsoni did not decrease the activities of hexokinase, glucose-6-phosphate dehydrogenase or 6-phosphogluconate dehydrogenase in canine reticulocytes, although it was previously reported that this serum had inhibitory effects on both the maturation of reticulocytes and the canine P5N-I and purine-specific 5'-nucleotidase activities. Furthermore, the in vitro multiplication of B. gibsoni was significantly inhibited by pyrimidine nucleotides such as cytidine 5'-monophosphate (5'-CMP), which is preferentially catalyzed by P5N-I and also inhibits the morphological maturation of canine reticulocytes. Purine nucleotides such as inosine 5'-monophospha te (5'-IMP) also had an inhibitory effect on the multiplication of this parasite. These results suggest that nucleotides such as 5'-CMP and 5'-IMP might accumulate in young erythrocytes and/or serum in dogs infected with B. gibsoni as a result of the decreased activity of erythrocyte 5'-nucleotidase, and the accumulation of these nucleotides might inhibit the multiplication of this parasite and simultaneously retard the maturation of reticulocytes. The results obtained from the in vitro examinations in the present study may partially clarify the relationship between low parasitemia and simultaneous reticulocytosis in vivo in canine babesiosis. KEY WORDS: Babesia gibsoni, erythrocyte 5'-nucleotidase, purine nucleotide, pyrimidine nucleotide, reticulocyte.

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“…Activity of P5N also correlated highly with other biological variables such as ZPP as shown in other studies 7,[16][17][18] . Acute, severe lead poisoning leads to a Coombs' negative hemolytic anemia with basophilic stippling indicating the accumulation of intracellular pyrimidine nucleotides due to the inhibition of P5N activity [6][7][8]19) . However, biological effects of P5N in workers who are neither exposed to so high level of lead nor show hemolytic anemia have been sketchy although P5N activity is also significantly inhibited by lead exposure in them, and shows good correlates with lead exposure.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Activity of Erythrocyte Pyrimidine 5'-Nucleotidase (P5N) in Lead Exposed Workers: With Focus on the Effect on Hemoglobin.

Kim¹,

Yoo²,

Lee³

et al. 2002

INDUSTRIAL HEALTH

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Anemia that accompanies lead poisoning is in part the result of various inhibitory effects of lead on heme biosynthesis. Lead also increases the rate of red blood cell destruction due to the profoundly depressed activities of erythrocyte pyrimidine 5'-nucleotidase (P5N) activities. We studied parameters of the two metabolic pathways in the workers exposed to lead to evaluate P5N in the lead exposed workers and which pathway has an effect on hemoglobin (Hb) level. 29 male workers in the secondary lead smelting as high exposure group, 46 male workers in the manufacturer of inorganic pigment as low exposure group and 56 clerical male workers from another plant as nonexposed group were studied. Activity of P5N, lead concentration in whole blood (PbB), zinc protoporphyrin (ZPP), Hb, and ferritin were determined. In the present study, P5N activity of nucleotide metabolic pathway correlated with Hb after controlling indices of iron deficiency anemia (ferritin) occurring concurrently and heme biosynthetic pathway (ZPP) in the high exposure group while heme biosynthetic pathway did not correlate with Hb after controlling other two variables in exposure groups. These findings suggest that P5N rather than heme biosynthetic pathway has a major effect on Hb level even in workers without manifest hemolytic anemia.

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Lead poisoning: association with hemolytic anemia, basophilic stippling, erythrocyte pyrimidine 5'-nucleotidase deficiency, and intraerythrocytic accumulation of pyrimidines.

Cited by 106 publications

References 30 publications

Biomarkers of Lead Exposure.

Biomarkers of Lead Exposure.

Inhibitory Effect of Pyrimidine and Purine Nucleotides on the Multiplication of <i>Babesia gibsoni</i>: Possible Cause of Low Parasitemia and Simultaneous Reticulocytosis in Canine Babesiosis

Evaluation of Activity of Erythrocyte Pyrimidine 5'-Nucleotidase (P5N) in Lead Exposed Workers: With Focus on the Effect on Hemoglobin.

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