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Down Syndrome Abstract
of the Month: June 1998

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Antioxidant enzymes and fatty acid status in erythrocytes of Down's syndrome patients.

Pastor MC, Sierra C, Dolade M, Navarro E, Brandi N, Cabre E, Mira A, Seres A
Clin Chem 1998 May;44(5):924-929

Hospital Universitario Germas Trias i Pujol, Badalona, Spain.

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The excess of genetic information in patients with Down's syndrome (DS) produces an increase in the catalytic activity of superoxide dismutase (SOD1), an antioxidant enzyme coded on chromosome 21. It has been suggested that an increase in oxidative stress in DS patients may cause adverse effects in the cell membranes through the oxidation of polyunsaturated fatty acids (PUFAs). The aim of this study was to evaluate the cellular antioxidant system by determining the catalytic activity of the SOD1, glutathione peroxidase (GPx), catalase (CAT), and glutathione reductase (GR) enzymes and the concentrations of alpha-tocopherol in red blood cells (RBCs) in a group of 72 DS patients. The profile of fatty acids in the phospholipids of RBC membranes was also evaluated. The activity of the erythrocyte antioxidant enzymes is significantly higher in the DS group than in the control group. No differences were observed in RBC alpha-tocopherol concentrations between the two groups studied. Long-chain n6 PUFA (C20:3n6, C20:4n6) concentrations were increased in DS patients, suggesting enhanced delta-6-desaturase activity. The long-chain n3 PUFA (docosahexenoic acid) does not appear to be affected by increased oxidative stress, probably because of the existence of compensatory antioxidant mechanisms.

My comments:

In cells, SOD converts free radicals to hydrogen peroxide, and catalase converts hydrogen peroxide to oxygen and water. In this study, the red blood cells showed the ability to increase the catalase activity to match the SOD overactivity. Glutathione peroxidase, which also converts hydrogen peroxide to water and oxygen, was also elevated but not nearly as muchg as the catalase. The authors conclude that there is no antioxidant enzyme imbalance in the red blood cells. (This doesn't mean that this imbalance may not exist in other cells.)

In previous studies, this increase in catalase has not been found. The authors speculate that this is because they measured the peroxidative acitivity of the enzyme, which is a more sensitive measurement, and others did not.

Also for the first time, the authors demonstrate that the activity of SOD decreases with age in people with DS.

There was no difference in red blood cell concentrations of vitamin E between those with Down syndrome and without in the study group. This also argues in favor of the lack of imbalance of antioxidant enzymes, since the vitamin E would be consumed in tissues where there was an imblaance.

The other part of this study dealt with the fatty acids in the membranes of the red blood cells. Cell membranes are made up of protein and fatty acids, and are at increased risk of oxidative damage from an imbalance of antioxidant enzymes within the cell. The authors found no evidence in the red blod cell membranes to reflect any oxidative damage.
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