In certain tissues, glutathione biosynthesis is connected to methionine metabolism via the trans-sulfuration pathway. The latter condenses homocysteine and serine to cystathionine in a reaction catalyzed by cystathionine beta-synthase followed by cleavage of cystathionine to cysteine and alpha-ketoglutarate by gamma-cystathionase. Cysteine is the limiting amino acid in glutathione biosynthesis, and studies in our laboratory have shown that approximately 50% of the cysteine in glutathione is derived from homocysteine in human liver cells. In this study, we have examined the effect of pro- and antioxidants on the flux of homocysteine through the trans-sulfuration pathway in the human hepatoma cell line, HepG2. Our studies reveal that pyrrolidine dithiocarbamate and butylated hydroxyanisole enhance the flux of homocysteine through the trans-sulfuration pathway as has been observed previously with the pro-oxidants, H(2)O(2) and tertiary butyl hydroperoxide. In contrast, antioxidants such as catalase, superoxide dismutase and a water-soluble derivative of vitamin E elicit the opposite effect and result in diminished flux of homocysteine through the trans-sulfuration pathway. These studies provide the first evidence for the reciprocal sensitivity of the trans-sulfuration pathway to pro- and antioxidants, and demonstrate that the upstream half of the glutathione biosynthetic pathway (i.e. leading to cysteine biosynthesis) is redox sensitive as is the regulation of the well-studied enzymes in the downstream half (leading from cysteine to glutathione), namely, gamma-glutamyl-cysteine ligase and glutathione synthetase.

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Objective: To share the experiences of graduating students as they learn to deliver a new medication review service in community pharmacies in Ontario, Canada. Practice description: Four graduating pharmacy students volunteered in different community pharmacies to learn how to navigate a new provincial program called MedsCheck, which pays pharmacists to do medication reviews. Each student selected his or her own practice site, including 2 independent community pharmacies, a grocery store chain pharmacy and a hospital outpatient pharmacy. Practice innovation: To help the students learn to deliver the new MedsCheck services, a faculty mentor met with them on a weekly basis. To reflect on doing MedsChecks in the “real world” and to elicit feedback from the online community, each student blogged about his or her experiences. Results: All 4 students felt that peer mentoring improved their ability to deliver MedsCheck services. They also identified a number of barriers to delivering the MedsChecks and helped each other try to overcome the barriers. Conclusion: MedsCheck is a new service in Ontario and is not easily implemented in the current pharmacy model of practice. Peer mentoring is a helpful way to share successes and overcome barriers to delivery. Can Pharm J 2013;146:33-38.

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