Pro-oxidant shift in glutathione redox state during aging
| Autor: | Igor Rebrin, Rajindar S. Sohal |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Senescence
Aging Glutamate-Cysteine Ligase Pharmaceutical Science Mitochondrion medicine.disease_cause Redox Article Antioxidants chemistry.chemical_compound Biosynthesis medicine Animals Humans Homocysteine Glutathione Disulfide Chemistry Glutathione Pro-oxidant Mitochondria Oxidative Stress Biochemistry Glutathione disulfide Energy Intake Oxidation-Reduction Oxidative stress |
| Zdroj: | Advanced Drug Delivery Reviews. 60:1545-1552 |
| ISSN: | 0169-409X |
| DOI: | 10.1016/j.addr.2008.06.001 |
| Popis: | The GSH:GSSG ratio, which is the primary determinant of the cellular redox state, becomes progressively more pro-oxidizing during the aging process due to an elevation in the GSSG content and a decline in the ability for de novo GSH biosynthesis. The K(m) of glutamate-cysteine ligase (GCL), the rate-limiting enzyme in de novo GSH biosynthesis, significantly increases during aging, which would adversely affect the ability for rapid GSH biosynthesis, especially under stressful conditions. Experimental studies suggest that age-related accumulation of homocysteine, an intermediate in the trans-sulfuration pathway, may be responsible for causing the loss of affinity between GCL and its substrates. Over-expression of GCL has been shown to prolong the life span of Drosophila by up to 50%, suggesting that perturbations in glutathione metabolism play a causal role in the aging process. |
| Databáze: | OpenAIRE |
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