Featured Research

from universities, journals, and other organizations

'Promiscuous' enzymes still prevalent in metabolism: Challenges fundamental notion of enzyme specificity and efficiency

Date:
August 30, 2012
Source:
University of California, San Diego
Summary:
Open an undergraduate biochemistry textbook and you will learn that enzymes are highly efficient and specific in catalyzing chemical reactions in living organisms, and that they evolved to this state from their “sloppy” and “promiscuous” ancestors to allow cells to grow more efficiently. This fundamental paradigm is being challenged in a new study by bioengineers who reported in the journal Science what a few enzymologists have suspected for years: many enzymes are still pretty sloppy and promiscuous, catalyzing multiple chemical reactions in living cells, for reasons that were previously not well understood.

Enzymes are often thought to be specific, catalyzing only one reaction in a cell (left). However, some more promiscuous enzymes have many functions and catalyze many reactions in a cell. This study shows that promiscuous enzymes play a larger part in cell growth than previously thought.
Credit: Image courtesy of University of California, San Diego

Open an undergraduate biochemistry textbook and you will learn that enzymes are highly efficient and specific in catalyzing chemical reactions in living organisms, and that they evolved to this state from their "sloppy" and "promiscuous" ancestors to allow cells to grow more efficiently. This fundamental paradigm is being challenged in a new study by bioengineers at the University of California, San Diego, who reported in the journal Science what a few enzymologists have suspected for years: many enzymes are still pretty sloppy and promiscuous, catalyzing multiple chemical reactions in living cells, for reasons that were previously not well understood.

In this study, the research team, led by Bernhard Palsson, Galetti Professor of Bioengineering at the UC San Diego Jacobs School of Engineering, brought together decades of work on the behavior of individual enzymes to produce a genome-scale model of E. coli metabolism and report that at least 37 percent of its enzymes catalyze multiple metabolic reactions that occur in an actively growing cell.

"We've been able to stitch all of the enzymes together into one giant model, giving us a holistic view of what has been driving the evolution of enzymes and found that it isn't quite what we've thought it to be," said Palsson.

When organisms evolve, it is the genes or proteins that change. Therefore, gene and protein evolution has classically been studied one gene at a time. However in this work, Palsson and his colleagues, introduce an important paradigm shift by demonstrating that the evolution of individual proteins and enzymes is influenced by the function of all of the other enzymes in an organism, and how they all work together to support the growth rate of the cell.

Using a whole-cell model of metabolism, the research team found that the more essential an enzyme is to the growth of the cell, the more efficient it needs to be; meanwhile, enzymes that only weakly contribute to cell growth can remain 'sloppy.' The study found three major reasons why some enzymes have evolved to be so efficient, while others have not:

Enzymes that are used more extensively by the organism need to be more efficient to avoid waste. To increase efficiency, they evolve to catalyze one specific metabolic reaction. When enzymes are responsible for catalyzing reactions that are necessary for cell growth and survival, they are specific in order to avoid interference from molecules that are not needed for cell growth and survival.

Since organisms have to adapt to dynamic and noisy environments, they sometimes need to have careful control of certain enzyme activities in order to avoid wasting energy and prepare for anticipated nutrient changes. Evolving higher specificity makes these enzymes easier to control.

"Our study found that the functions of promiscuous enzymes are still used in growing cells, but the sloppiness of these enzymes is not detrimental to growth. They are much less sensitive to changes in the environment and not as necessary for efficient cell growth," said Nathan Lewis, who earned a Ph.D. in bioengineering at the Jacobs School in March and is now a postdoctoral fellow at Harvard Medical School.

This study is also a triumph in the emerging field of systems biology, which leverages the power of high-performance computing and an enormous amount of available data from the life sciences to simulate activities such as the rates of reactions that break down nutrients to make energy and new cell parts. "This study sheds light on the vast number of promiscuous enzymes in living organisms and shifts the paradigm of research in biochemistry to a holistic level," said Lewis. "The insights found in our work also clearly show that fine-grained knowledge can be obtained about individual proteins while using large-scale models." This concept will yield immediate and more distant results.

"Our team's findings could also inform other research efforts into which enzymes require further study for overlooked promiscuous activities," said Hojung Nam, a postdoctoral researcher in Palsson's lab. "Besides testing and characterizing more enzymes for potential promiscuous activities, enzyme promiscuity could have far-reaching impacts as scientists try to understand how unexpected promiscuous activities of enzymes contribute to diseases such as leukemia and brain tumors," said Nam.

Funding was provided by the U.S. Department of Energy and National Institutes of Health (DE-SC0004917, DE-FG02-09ER25917, and 2R01GM057089-13) and a fellowship from the National Science Foundation (NSF GK-12 742551).


Story Source:

The above story is based on materials provided by University of California, San Diego. Note: Materials may be edited for content and length.


Journal Reference:

  1. H. Nam, N. E. Lewis, J. A. Lerman, D.-H. Lee, R. L. Chang, D. Kim, B. O. Palsson. Network Context and Selection in the Evolution to Enzyme Specificity. Science, 2012; 337 (6098): 1101 DOI: 10.1126/science.1216861

Cite This Page:

University of California, San Diego. "'Promiscuous' enzymes still prevalent in metabolism: Challenges fundamental notion of enzyme specificity and efficiency." ScienceDaily. ScienceDaily, 30 August 2012. <www.sciencedaily.com/releases/2012/08/120830152303.htm>.
University of California, San Diego. (2012, August 30). 'Promiscuous' enzymes still prevalent in metabolism: Challenges fundamental notion of enzyme specificity and efficiency. ScienceDaily. Retrieved October 2, 2014 from www.sciencedaily.com/releases/2012/08/120830152303.htm
University of California, San Diego. "'Promiscuous' enzymes still prevalent in metabolism: Challenges fundamental notion of enzyme specificity and efficiency." ScienceDaily. www.sciencedaily.com/releases/2012/08/120830152303.htm (accessed October 2, 2014).

Share This



More Plants & Animals News

Thursday, October 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Study Says Losing Sense Of Smell Can Indicate Death

Study Says Losing Sense Of Smell Can Indicate Death

Newsy (Oct. 2, 2014) — Researchers found elderly adults with a poor sense of smell are more likely to die within five years. Video provided by Newsy
Powered by NewsLook.com
Dolphins and Turtles Under Threat in Pakistan

Dolphins and Turtles Under Threat in Pakistan

AFP (Oct. 2, 2014) — The turtles and Dolphins of Pakistan's Indus river - both protected by law - are in a fight for their survival as man's activities threatens their futures. Duration: 02:29 Video provided by AFP
Powered by NewsLook.com
'Harvest Break' Endures in Maine Potato Fields

'Harvest Break' Endures in Maine Potato Fields

AP (Oct. 2, 2014) — Educators and farmers are clinging to a tradition aimed at giving farmers much-needed help in getting potatoes out of the fields and into storage before the ground freezes in the nation's northeast corner. (Oct. 2) Video provided by AP
Powered by NewsLook.com
Attacking Superbugs

Attacking Superbugs

Ivanhoe (Oct. 1, 2014) — Two weapons hospitals can use to attack superbugs. Scientists in Ireland created a new gel resistant to superbugs, and a robot that can disinfect a room in minutes. Video provided by Ivanhoe
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins