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Erythrocyte nucleotides in children--increased blood lead and cytidine triphosphate
Insights
High blood lead levels in children significantly increase erythrocyte cytidine phosphates and decrease pyrimidine 5'-nucleotidase (P5N) activity. These changes correlate with lead exposure, impacting nucleotide metabolism.
Area of Science:
- Biochemistry
- Toxicology
- Pediatrics
Background:
- Erythrocyte nucleotide metabolism is crucial for cellular function.
- Lead (Pb) exposure in children can disrupt biochemical pathways.
- Pyrimidine 5 extapostrophe-nucleotidase (P5N) is an enzyme involved in nucleotide degradation.
Purpose of the Study:
- To investigate the impact of varying blood lead levels (PbB) on erythrocyte nucleotide profiles in young children.
- To assess the relationship between lead exposure, P5N activity, and specific nucleotide concentrations.
Main Methods:
- Anion-exchange high-performance liquid chromatography was used to assay erythrocyte nucleotides.
- Blood lead levels (PbB) were measured in 25 children aged 1-5 years.
- Pyrimidine 5 extapostrophe-nucleotidase (P5N) activity and erythrocyte zinc protoporphyrin were quantified.
Main Results:
- Children with PbB ≥ 30 µg/dL showed significantly increased erythrocyte cytidine phosphates (CMP, CDP, CTP) compared to those with lower PbB.
- P5N activity was significantly lower in children with higher PbB.
- Strong correlations were observed between PbB, cytidine phosphates, P5N activity, and erythrocyte zinc protoporphyrin.
Conclusions:
- Elevated blood lead levels in children are associated with altered erythrocyte nucleotide metabolism, specifically increased cytidine phosphates.
- Reduced P5N activity is a key indicator of lead toxicity in children's erythrocytes.
- These findings highlight the biochemical consequences of lead exposure on nucleotide homeostasis in pediatric populations.
Abstract:
The erythrocyte nucleotides of 25 children, 1-5 years old, with normal and increased blood leads, were assayed by anion-exchange high-performance liquid chromatography. Red blood cells of the 12 children with blood lead (PbB) below 30 micrograms/dl (20.3 +/- 6 micrograms/dl, mean +/- S.D.) had normal levels of activity of pyrimidine 5'-nucleotidase (P5N) and their erythrocytes were virtually free of pyrimidine nucleotides except for small amounts of UMP and UDP. The purine nucleotides, predominantly ATP and GTP, were present at values similar to adults. In the 13 children with PbB 30-72 micrograms/dl (45.3 +/- 14.3 micrograms/dl), total cytidine phosphates (CMP, CDP, CTP) were significantly (P less than 0.001) increased from trace values to 8.31 +/- 6.21 nmoles/10(10) erythrocytes. The purine nucleotides were unchanged. P5N activity was 143.3 +/- 22.0 units/g hemoglobin in children with PbB less than 30 micrograms/dl and 75.4 +/- 24.2 units (P less than 0.001) in the high lead subjects. There was a logarithmic correlation of erythrocyte cytidine phosphates with PbB (r = 0.89, P less than 0.001) and an inverse correlation of cytidine phosphates with ln P5N activity (r = 0.59, P less than 0.001), of ln P5N with PbB (r = 0.64, P less than 0.001) and of ln P5N with ln erythrocyte zinc protoporphyrin (Protoporphyrin IX) (r = 0.57, P less than 0.001).