Department of Biochemistry
Universidad Nacional Autónoma de México
A generation ago, protein scientists followed a straightforward paradigm: “one protein, one structure, one function.” But research now has revealed that moonlighting is not restricted to struggling Hollywood actors. Several protein families have developed a degree of promiscuity and can carry out activities not related to their main functions.
The actual paradigm goes something like, “one protein sequence, several structures, many functions.”
Hector Riveros-Rosas can take pride in the fact that he played a role in shifting this paradigm when he showed that alcohol-metabolizing enzymes might have evolved differently than people had thought.
It all began back when Riveros-Rosas was an undergraduate at the Universidad Nacional Autónoma de México. He was invited to participate in a research project studying the metabolic effects of chronic ethanol administration on isolated rat liver mitochondria.
That independent work solidified his interests in biochemistry, particularly alcohol metabolism, and he continued his research career at UNAM School of Medicine, first receiving his master's in 1996 and his doctorate in 2004.
During this time, while studying the properties of the main enzymes involved in alcohol metabolism, alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs), he observed that ADHs could utilize a huge diversity of alcohols as substrates. Other groups also had found that ADHs display higher catalytic efficiency for many endogenous substrates, such as retinol, steroids and dopamine.
“Thus, we proposed that the main physiological role of ADHs is the metabolism of these important endogenous substrates, and not ethanol oxidation,” he says.
To help validate this conclusion, Riveros-Rosas began to investigate the evolutionary history of ADHs. He and colleagues uncovered a big piece of evidence when they showed that the origin of ADHs predates the major natural dietary source of ethanol (fermentation of fruit sugar by yeast). Thus, ethanol availability could not be a selective force that directed the evolution of these proteins.
This discovery seemed unexpected given that the presence of ADHs in animals had been assumed to be a consequence of chronic exposure to ethanol. However, if the origin of the different ADHs predates the origin of angiosperms with fleshy fruits, then perhaps, ethanol metabolism was not an adaptive function in animals but just an incidental one.