New enzyme discovered in mammals

Mammals, there’s a new enzyme in town. In a paper just published in the Proceedings of the National Academy of Sciences, scientists report the discovery of a new enzyme called glycerol-3-phosphate phosphatase. The enzyme plays a critical role in metabolism by overseeing the levels of different fuels in the body.

Metabolism has been a heavily trodden field of study ever since the dawn of molecular biology. These days, “it is extremely rare that a novel enzyme is discovered at the heart of intermediary metabolism in all mammalian tissues,” says S.R. Murthy Madiraju at the Montreal Diabetes Research Center, one of the corresponding authors on the paper.

Madiraju, along with Marc Prentki at the Montreal Diabetes Research Center and others, found the enzyme while grappling with a puzzle. They were studying pancreatic beta cells that produce insulin to control blood glucose levels. These cells get stressed when barraged with metabolic fuel from the diet, such as glucose and fatty acids. When that happens, the cells make and get rid of glycerol as a way of dealing with the excessive fuel supply.

Initially researchers thought the glycerol came from the breakdown of fats. But when Madiraju, Prentki and colleagues inhibited fat breakdown, the cells kept making glycerol. This suggested there was another glycerol source.

Microorganisms, plants and some fish have an enzyme that turns a molecule called glycerol-3-phosphate into glycerol. Mammals were thought not to have the enzyme.

But the investigators set out to check if mammals really and truly didn’t have a glycerol-3-phosphate phosphatase. It turns out they do. Madiraju, Prentki and colleagues confirmed the presence of the enzyme both in cell and animal models.

In discovering a mammalian glycerol-3-phosphate phosphatase, “we have to re-adjust our thinking that fat breakdown is not the only way by which mammalian cells generate glycerol, as has been believed so far!” says Prentki.

Glycerol-3-phosphate, the molecule on which the enzyme works, is made from glucose and gets incorporated into fats. It lies at the heart of glucose and lipid metabolism. With the discovery of an enzyme that can directly break down glycerol-3-phosphate, researchers now have a new player to contend with in understanding how the body maintains energy levels under normal circumstances and what goes wrong in different metabolic diseases.

The investigators say that they believe that, because of its critical metabolic role, glycerol-3-phosphate phosphatase will be a new target for treating chronic conditions such as obesity and type 2 diabetes as well as some cancers.