New Technologies For Extracorporeal Enzymatic Detoxification

Abstract

Extracorporeal enzymatic detoxification for support of failing organ function requires long-term applicability of such enzymes for hours or even days. Different approaches towards this aim have been reported (Chang, 1969; Brunner and Jaworek, 1976; Schmer et al., 1981). The physiological detoxification of the majority of endogenous toxins requires phase I and phase II reactions and high energetic cofactors like uridine disphosphoglucuronic acid (UDPGA), nicotinamide adenine dinucleotide phosphate (reduced form, NADPH), nicotinamide adenine dinucleotide (reduced form, NADH), adenosine triphosphate (ATP), 5-adenosyl-L-methionine (SAM). Enzyme immobilisation was initially an essential step in using these enzymes in biological fluids to prevent immunological reactions. However, immobilisation results in a significant loss of enzyme activity and cofactor supply is a costly problem. Until now cofactors had to be constantly infused into the enzymatic reaction systems or agarose beads were soaked in cofactor solutions prior to application which allowed catalytic activities up to one hour. With both methods, large amounts of expensive cofactors were wasted. For long-term enzymatic detoxification reactions, as required in hepatic failure, for example, both methods are not suitable. Therefore, improved