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Reduction of dehydroascorbic acid by homocysteine
1Phytonutrients Laboratory, Bldg. 307, Rm. 313, BHNRC, ARS, USDA, Beltsville, MD 20705, USA. park@307.bhnrc.usda.gov
Biochimica Et Biophysica Acta
|May 9, 2001
Summary
Homocysteine efficiently reduces dehydroascorbic acid to ascorbic acid at low concentrations. This extracellular reduction impacts cellular uptake and DNA synthesis, offering new insights into vitamin C metabolism.
Area of Science:
- Biochemistry
- Cell Biology
- Nutritional Science
Background:
- Dehydroascorbic acid (DHA) is the oxidized form of ascorbic acid (AA), crucial for cellular functions.
- Understanding the extracellular reductive processes of DHA is vital for comprehending AA bioavailability and cellular uptake.
- Homocysteine (Hcy) is an amino acid with potential redox activity, but its role in DHA reduction is not fully elucidated.
Purpose of the Study:
- To investigate the potential of various molecules, including homocysteine, to reduce extracellular dehydroascorbic acid to ascorbic acid.
- To compare the efficacy of homocysteine with other reducing agents like reduced glutathione (GSH) and cysteine (Cy).
- To explore the impact of extracellular homocysteine-mediated DHA reduction on cellular uptake and DNA synthesis.
Main Methods:
- In vitro assays were performed to test the reductive capacity of homocysteine, homocysteine thiolactone, methionine, cysteine, and homoserine on DHA.
- Comparative analysis of DHA reduction by homocysteine, GSH, and cysteine at varying concentrations.
- Cellular studies using Jurkat, U937, and human umbilical vein endothelial cells to assess DHA uptake and DNA synthesis in the presence of homocysteine and quercetin.
Main Results:
- Homocysteine demonstrated potent stoichiometric reduction of DHA to AA at concentrations as low as 10 micromol/l, significantly outperforming GSH and cysteine.
- Increased extracellular homocysteine suppressed intracellular DHA uptake, indicating competition for available DHA.
- Extracellular reduction of DHA by homocysteine protected human umbilical vein endothelial cells from Hcy-induced decrease in DNA synthesis.
Conclusions:
- Homocysteine is a highly effective extracellular reductant for dehydroascorbic acid, converting it to ascorbic acid.
- Extracellular reduction by homocysteine influences the availability of DHA for cellular uptake and may play a role in cellular protection.
- These findings highlight a novel biochemical pathway involving homocysteine in ascorbic acid metabolism and cellular redox homeostasis.