SAT-1709 Inhibitions of rLactose Dehydrogenase (rLDH) and rPhosphofructokinase-1 (rPFK-1) Enzyme Activities by Ascorbic Acid 6-Butyrate (AAB) and Ascorbic Acid 2,6-Dibutyrate (AADB)

Saturday, October 13, 2012: 1:20 PM
Hall 4E/F (WSCC)
Mary Graves , Chemistry, San Diego Mesa College, San Diego, CA
Edward Alexander, PhD , Chemistry, San Diego Mesa College, San Diego, CA
Percy Russell, PhD , Biology, University of California, San Diego, La Jolla, CA
Alberto Palacios , Chemistry, San Diego Mesa College, San Diego, CA
Abdirisak Hussein , Chemistry, San Diego Mesa College, San Diego, CA
Mohamed Musse , Chemistry, San Diego Mesa College, San Diego, CA
Anita Williams, BS , Biology, University of California, San Diego, La Jolla, CA
Ami Abbott , Biology, University of California, San Diego, La Jolla, CA
Pham Duyen Anh , University of California, San Diego, La Jolla, CA
 

Ascorbic acid (AA) is an essential nutrient and natural antioxidant. Studies have shown that AA inhibits the activity of the glycolytic enzymes r-Phosphofructokinase-1 (rPFK-1), and r-Lactate Dehydrogenase (rLDH). While (AA) is unstable under physiological conditions, its fatty acid derivatives are stable and can induce apoptosis in cancer cells. The purpose of this research was to investigate the inhibitions of the AA fatty acid derivatives, Ascorbic Acid-6-Butyrate (AAB) and Ascorbic Acid 2, 6-Dibutyrate (AADB) towards (rPFK-1) and (rLDH). Our hypothesis was that the inhibitions of (AA) and (AA) fatty acid derivatives were due to antioxidation by the 2, 3-ene-diol group and allosteric effects of lipophilic side chains. (AAB) was synthesized from (AA) and butyric acid. The (AAB) inhibitions of (rPFK-1) and (rLDH) were determined. Inhibition studies were carried out on L-Gulonic Gamma Lactone (LGGL) and methyl and ethyl butyrates. Antioxidations were tested using DCPIP (2, 6-dichlorobenzenoneindophenol). Our results showed: AAB is seventy- three times more inhibitory than AA, three times more inhibitory than (AADB) for (rLDH); and is two times more inhibitory than AA, nine times more inhibitory than (AADB) for (rPFK-1). (LGGL), and methyl and ethyl butyrates showed no inhibitions. (AAB) underwent oxidation with DCPIP. (LGGL) underwent no oxidation; (AADB) underwent oxidation at elevated temperatures and hydrolyzed to (AAB). Our results support the hypothesis that the mechanism for inhibition by (AA) and (AAB) involves antioxidation by the 2, 3-ene-diol, and allosteric destabilization of enzymes’ active configurations by lipophilic side chains. (AADB) inhibitions appear to involve an additional hydrolysis step.