Environmental assessment of enzyme assisted processing in pulp and paper industry

Background Aims and Scope  The pulp and paper (P&P) industry is traditionally known to be a large contributor to environmental pollution due its large consumptions of energy and chemicals. Enzymatic processing, however, offers potential opportunities for changing the industry towards more environmentally friendly and efficient operations compared to the conventional methods. The aims of the present study has been to investigate whether the enzyme technology is a more environmentally sound alternative than the conventional ways of producing paper. The study addresses five enzyme applications by quantitative means and discusses the environmental potential of a range of other enzyme applications by qualitative means. Methods  LCA is used as analytical tool and modelling is facilitated in SimaPro software. Foreground LCA data are production/company specific and collected from P&P technology service providers, specific P&P companies and P&P researchers. The background data on energy systems, auxiliary chemicals, etc. are primarily taken from the ecoinvent database. Results  The study shows that fossil energy consumption and potential environmental impacts (global warming, acidification, nutrient enrichment, photochemical smog formation) induced by enzyme production are low compared with the impacts that they save when applied in bleach boosting, refining, pitch control, deinking, and stickies control. Discussion  The general explanation is that small amounts of enzyme provide the same function as large amounts of chemicals and that enzymatic processes generally require less fossil energy inputs than conventional processes. Data quality assessments and sensitivity analyses indicate that this observation is robust for all processes except deinking, although the results are subject to uncertainty and much variation. Conclusions and Recommendations  The environmental improvements that can be achieved by application of enzymatic solutions in the P&P industry are promising. To get a greater penetration of enzymatic solutions in the market and to harvest the environmental advantages of biotechnological inventions, it is recommended that enzymatic solutions should be given more attention in, for instance, ‘Best Available Technology’ notes within the framework of the European Directive on Integrated Pollution Prevention and Control (IPPC). ESS-Submission Editor: Roland Hischier (roland.hischier@empa.ch)     

The anti-cancer drug chlorambucil as a substrate for the human polymorphic enzyme glutathione transferase P1-1: kinetic properties and crystallographic characterisation of allelic variants

The commonly used anti-cancer drug chlorambucil is the primary treatment for patients with chronic lymphocytic leukaemia. Chlorambucil has been shown to be detoxified by human glutathione transferase Pi (GST P1-1), an enzyme that is often found over-expressed in cancer tissues. The allelic variants of GST P1-1 are associated with differing susceptibilities to leukaemia and differ markedly in their efficiency in catalysing glutathione (GSH) conjugation reactions. Here, we perform detailed kinetic studies of the allelic variants with the aid of three representative co-substrates. We show that the differing catalytic properties of the variants are highly substrate-dependent. We show also that all variants exhibit the same temperature stability in the range 10 °C to 45 °C. We have determined the crystal structures of GST P1-1 in complex with chlorambucil and its GSH conjugate for two of these allelic variants that have different residues at positions 104 and 113. Chlorambucil is found to bind in a non-productive mode to the substrate-binding site (H-site) in the absence of GSH. This result suggests that under certain stress conditions where GSH levels are low, GST P1-1 can inactivate the drug by sequestering it from the surrounding medium. However, in the presence of GSH, chlorambucil binds in the H-site in a productive mode and undergoes a conjugation reaction with GSH present in the crystal. The crystal structure of the GSH-chlorambucil complex bound to the *C variant is identical with the *A variant ruling out the hypothesis that primary structure differences between the variants cause structural changes at the active site. Finally, we show that chlorambucil is a very poor inhibitor of the enzyme in contrast to ethacrynic acid, which binds to the enzyme in a similar fashion but can act as both substrate and inhibitor.     

The role of erythropoietin and its receptor in growth,survival and therapeutic response of human tumor cells: From clinic to bench — a critical review

Recombinant human erythropoietin (rhEPO) has been used clinically to alleviate cancer- and chemotherapy-related anemia. However, recent clinical trials have reported that rhEPO also may adversely impact disease progression and survival. The expression of functional EPO receptors (EPOR) has been demonstrated in many human cancer cells where, at least in vitro, rhEPO can stimulate cell growth and survival and may induce resistance to selected therapies.