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Expression of gamma-glutamylcysteine synthetase during development
A L Levonen1, R Lapatto, M Saksela
1Hospital for Children and Adolescents, University of Helsinki, Finland.
Pediatric Research
|February 16, 2000
Summary
Low glutathione (GSH) levels in preterm infants are not due to deficient GSH synthesis. The enzyme responsible for GSH production, gamma-glutamylcysteine synthetase (GCS), is active early in development.
Area of Science:
- Biochemistry
- Developmental Biology
- Neonatology
Background:
- Prematurity is linked to reduced glutathione (GSH) levels in various biological samples.
- The cause of these low GSH concentrations in preterm neonates remains unclear.
Purpose of the Study:
- To investigate if deficient GSH synthesis contributes to low GSH levels in preterm infants.
- To examine the expression and activity of gamma-glutamylcysteine synthetase (GCS), the rate-limiting enzyme in GSH synthesis, across different human developmental stages.
Main Methods:
- Human fetal, neonatal, and adult liver, lung, and kidney samples were analyzed.
- Expression of GCS heavy and light subunits (mRNA) and enzyme activity were measured.
Main Results:
- GCS is expressed and active from the second trimester of gestation.
- Liver GCS activity and mRNA expression were consistent across developmental stages.
- Lung GCS light subunit mRNA was higher in neonates, but enzyme activity remained similar.
- Kidney GCS activity showed a slight increase in adults, with considerable sample variation.
Conclusions:
- Deficient GSH synthesis does not explain low GSH concentrations in preterm neonates.
- Alternative factors like limited cysteine availability or increased GSH consumption likely contribute to lower GSH levels in preterm infants.