1

Purines a-ketogluterate ¡Z

Antioxidant enzyme response pathway (SOD/CAT)

Figure 7.7 Proline linked pentose-phosphate pathway in eukaryotes for regulating antioxidant response.

interact with the receptors on the cell surface responsible activating biological signal transduction processes. Recent empirical evidence has now shown that some phenolic phytochemicals can also mimic the functions of biological signaling molecules and trigger the signal transduction (153,164,165). Phenolics from cranberry, especially biphenyls and flavo-noids are large and partially hydrophobic, and can be perfect candidates for the activating signaling pathways responsible for the stimulation of PPP (153,164,165). In addition, phenolic phytochemicals such as ellagic acid and flavonoids from cranberry have been known to be good chelators; these phytochemicals can effectively chelate the ions such as calcium in the extracellular matrix (ECM) or in the cytosol and alter the net concentration of free calcium (8,166,167). Calcium in the cytosol and extracellular matrix is critical for maintaining cellular homeostasis and is an important factor in regulating cell division and cell death, and is often regulated by the calcium sensing receptor (168-172). Many cellular signaling cascades are sensitive to a calcium gradient across the cell membrane (171,172). An apparent modulation in the concentration of calcium, either by calcium binding or by the modulating the calcium sensing receptor, can activate these cellular signaling cascades which can result in changes in many physiological pathways including the stimulation of the PPP (161, 171-173). Phenolic phytochemicals such as ellagic acid and flavonoids have been shown to interact with proteins and alter their configuration. These phytochemicals can therefore directly interact with the cell surface receptors and ion pumps, and directly activate signaling cascades by inducing structural changes in the membrane receptor proteins and pumps (174-177). Phenolic phytochemicals, especially phenolic acids, are weak acids and are capable of dissociating at the cell membrane at a biological pH of 6.8-7.2 (178). This dissociation can create a proton gradient across the cell membrane which can alter the function

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