A cure for drunkenness?

Enzymes are biocatalysts that mediate every biological process in living organisms. Most enzymes do not roam freely within the cell but are carefully positioned together within subcellular compartments along with complementary enzymes. This allows toxic intermediates generated by one enzyme to be promptly eliminated by another enzyme before it can diffuse into the cell.

Inspired by these clusters of complementary enzymes, a team of researchers led by Yunfeng Lu (University of California, Los Angeles) employed a new technique to assemble and encapsulate multiple enzymes with complementary functions within a thin polymer shell to form an enzyme nanocomplex (Nat. Nanotechnol. doi:10.1038/nnano.2012.264; published online 17 February 2013). To combine the enzymes, the researchers attached inhibitors of each enzyme to the ends of a single-stranded DNA scaffold. When the enzymes are mixed with the scaffold, they bind to their respective inhibitors and form the nanocomplex. Then a thin layer of polymer is grown around the nanocomplex to protect it. Finally, the DNA-inhibitor scaffold is removed so that the enzymes are free to catalyze reactions.

Excessive consumption and abuse of alcohol is associated with a range of organ injuries and social problems. The scientists constructed a nanocomplex that could be used to reduce blood alcohol levels as an antidote and prophylactic for alcohol intoxication in mice. The nanocomplex was constructed to combine alcohol oxidase (AOx), which breaks down alcohol but produces toxic hydrogen peroxide (H₂O₂) as a byproduct, and catalase (Cat), which is highly active and specific in decomposing H₂O₂. By packaging them together in the complex, Cat effectively removes the generated H₂O₂ and prevents it from inactivating the AOx.

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In prophylactic studies, mice that were fed a combination of alcohol and the nanocomplex had significantly reduced blood alcohol content (BAC). The reduction increased over time and was greater than in mice that were fed alcohol with just one of the enzymes or in mice that were fed alcohol and both enzymes in separate complexes. A dose-dependence study suggested that BAC decreased with increasing doses of the nanocomplex. To test whether the nanocomplex could act as an antidote to alcohol intoxication, the nanocomplex was injected into the tail vein of intoxicated mice. The treated mice had the largest BAC reduction and showed the lowest levels of an enzyme biomarker for liver damage.

The authors propose that such enzyme complexes could be built for a variety of applications, given the vast range of enzymes that are currently or potentially available.