Plasma ascorbic acid concentrations may be low in chronic or acute oxidant

Plasma ascorbic acid concentrations may be low in

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Plasma ascorbic acid concentrations may be low in chronic or acute oxidant states such as in diabetes, in smokers, or following acute pancreatitis or myocardial infarction. Ascorbic acid is easily oxidized to the unstable dehydroascorbic acid. Dehydroascorbic acid is not normally detectable in plasma but may occur transiently during oxidant stress. Ascorbic acid is transported into the cell by sodium-dependent vitamin C transporters SVCT1 and SVCT2, one or both of which are found in most tissues. 6 Dehydroascorbic acid is transported by glucose transporters GLUT1 and GLUT3, and, in insulin-sensitive tissues, also by GLUT4. When exposed to bacteria, neutrophils oxidize extracellular ascorbic acid to form dehydroascorbic acid, which is transported into the neutrophil and rapidly reduced to ascorbic acid by the protein glutaredoxin ( Fig. 1 ). As a result of this recycling of extracellular ascorbic acid, the neutrophil internal concentration of ascorbic acid increases 10-fold. 7 Ascorbic acid may quench oxidants generated during phagocytosis and, thus, protect the neutrophil and surrounding tissues from oxidative damage. Brain, adrenal cortex, liver, spleen, pancreas and kidney tissues concentrate vitamin C for unknown reasons. View larger version (47K): In this window
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In a new window Fig. 1: Ascorbic acid (AA) transport, dehydroascorbic acid (DHA) transport and recycling in human neutrophils. AA, transported by sodium-dependent vitamin C transporters (SVCT), maintains mmol/L concentrations of AA inside neutrophils. Activated neutrophils secrete reactive oxygen species that oxidize extracellular AA to DHA. DHA is rapidly transported into the neutrophil by the glucose transporters GLUT1 and GLUT3 and immediately reduced to AA by glutaredoxin (GRX), producing a 10-fold increase in neutrophil internal AA concentration. Glutathione (GSH), used during DHA reduction, is regenerated from glutathione disulfide (GSSG) by glutathione reductase (GRD) and NADPH. NADPH is a product of glucose metabolism through the pentose phosphate pathway. As NADPH is oxidized to NADP, electrons are transferred to GRD so it can reduce GSSG to GSH. Modified and reproduced with permission of the Journal of Nutritional Biochemistry 1998;9:120, 7 Elsevier Sciences Inc. When given orally, ascorbic acid is well absorbed at lower doses, but absorption decreases as the dose increases. Thus, median bioavailability following an oral dose is 87% for 30 mg, 80% for 100 mg, 72% for 200 mg and 63% for 500 mg. Less than 50% of a 1250-mg dose is absorbed, and most of the absorbed dose is excreted in the urine. 3 , 8 Ascorbic acid is not protein bound, so it is filtered and reabsorbed by the kidneys in healthy subjects but is lost in patients who have been hemodialyzed. Ascorbic acid begins to appear in urine at doses above 100 mg/day, corresponding to a plasma concentration of about 60 µmol/L, at which point plasma is 70% saturated and circulating white blood cells are fully saturated. Decreased bioavailability and renal excretion keep plasma vitamin C at less than 100 µmol/L, even with an oral dose of 1000 mg. In men at
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