Ascorbic acid is a stimulatory cofactor for mitochondrial glycerol-3-phosphate dehydrogenase.
Mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) from control and scorbutic guinea pig brain, liver and skeletal muscle and from normal rat liver was stimulated several fold by l-ascorbic acid (AA). The amount of AA that gave half-maximal stimulation of guinea pig brain mGPDH was 7.1 microM. At concentrations of AA higher than 500 microM, mGPDH activity decreased to nearly the same activity as in the absence of AA. D-Ascorbic acid, erythorbic acid, was equally potent in the activation of washed mitochondrial mGPDH activity. The AA activation of mGPDH was completely inhibited by 50 microM EGTA, but could be fully restored by the sequential addition of 100 microM Ca2+. The AA activation of mGPDH was likewise completely inhibited by iron specific chelators, bathophenanthrolinedisulfonic acid, desferrioxamine, and 1,10-phenanthroline, but the activation could not be restored by the addition of excess Ca2+. In the absence of AA, mGPDH activity was not inhibited by either EGTA or the iron chelators and Ca2+ addition had no effect on the activity. The iron-sulfur protein, succinic dehydrogenase (complex II), was not significantly different in brain mitochondria from control or scorbutic guinea pigs, and was not activated by the subsequent addition of AA. In the presence of AA, succinic dehydrogenase activity was not affected by either bathophenanthrolinedisulfonic acid or EGTA. The results suggest that mGPDH is a probable site of action of AA in the related glucose-coupled insulin release from pancreatic islets.
Jung
C H
CH
Department of Biochemistry, Michigan State University, East Lansing 48824, USA.
Wells
W W
WW
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism*; D006168:Guinea Pigs; D007502:Iron Chelating Agents / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D013385:Succinate Dehydrogenase / Q000378:metabolism
D007502:Iron Chelating Agents; D005993:Glycerolphosphate Dehydrogenase; D013385:Succinate Dehydrogenase; D001205:Ascorbic Acid