Humans and many animals are unable to breakdown oxalate, a molecule that is found is many fruits and vegetables, leading to its buildup and subsequent health problems such as arthritis, kidney stones and sometimes kidney failure. Now, scientists from the Massachusetts Institute of Technology have discovered a previously unknown mechanism that allows for the breakdown of oxalate and may therefore aid in reducing it's harmful effects in humans.
The team of researchers utilized X-ray crystallography to identify how the thiamine pyrophosphate-dependent oxalate oxidoreductase (OOR) enzyme metabolizes oxalate using a unique mechanism that breaks apart the molecule.
"This is unprecedented chemistry, what this enzyme does," Catherine Drennan, who participated in the research, said in a press release. "This particular enzyme just takes it [oxalate] and splits it. It's always fantastic when the structure shows you the answer and it's something you never guessed."
The OOR enzyme is a massive, complex molecule that binds with oxalate in a way that neutralizes its negative charges as well as breaks its carbon-carbon bond that lies at its core, leading to its breakdown.
"There are [just] these two movements," said Drennan. "The simplest things are the most elegant and beautiful."
The scientists were able to use X-ray crystallography to reveal the molecular structure of OOR at the atomic level, allowing them to determine the unique way that OOR metabolizes oxalate.
"By solving a number of structures, I call them snapshots, we can watch in a way the action take place, because we have a series of pictures at various different time-points along the reaction mechanism," Drennan said. "And that's super-cool. I think my favorite thing about crystallography is when you can do that."
In the future, the researchers hope to further explore the effects of these processes on human health issues.
"We have kind of been ignoring this huge aspect of human health," Drennan said. "I think as we start understanding the importance of those microbes [that are] doing chemistry for us, I think we're going to really appreciate it."
The findings were published in the Nov. 23 issue of the Proceedings of the National Academy of Sciences.
