Metabolic reactions: Less is more in single-celled organisms

December 05, 2008

All single-celled organisms are not alike. Or are they?

A Northwestern University study has found a surprising similarity among four quite different organisms. The simplest organism, a bacterium called H. pylori, uses the same number of biochemical reactions (around 300) as yeast, the largest, most complex organism of the group, when optimizing growth.

The other surprising finding is that to optimize, or efficiently perform, metabolic tasks, such as growing fast or converting sugars to ethanol, the organisms tend to use only a small fraction of the biochemical reactions available to them in the metabolic network. Less efficient, or suboptimal, behavior tends to use a much larger number of reactions.

The results contribute a new understanding of the interplay between metabolic network activity and biological function and indicate there is a general behavior that is common to diverse organisms.

The research was led by Adilson E. Motter, assistant professor of physics and astronomy in Northwestern's Weinberg College of Arts and Sciences; the study will be published Friday, Dec. 5, by the journal PLoS Computational Biology, an open-access, online journal published by the Public Library of Science.

Motter's collaborators and co-authors of the paper, titled "Spontaneous Reaction Silencing in Metabolic Optimization," are Takashi Nishikawa, formerly a visiting scholar at Northwestern, now of Clarkson University, and Natali Gulbahce, of Northeastern University and the Dana Farber Cancer Institute.

Little is known about what the individual parts of the cell do in relation to the whole organism. These new findings -- that many of the parts, or chemical reactions, are shut down spontaneously for the cell to perform optimally -- provide an area of focus to scientists who want to control cell behavior by manipulating one or more biochemical reactions.

The knowledge may help researchers genetically engineer cells or treat sick cells. Yeast, for example, is used to produce ethanol, so to increase production the research indicates how shutting down some of the cell's biochemical reactions could force the cell to produce ethanol more efficiently. The identification of drug targets and the development of new therapies also often require manipulating molecular reactions to produce a desirable outcome.

"Each organism is a very versatile chemical factory," said Motter, who is also a member of the Northwestern Institute on Complex Systems. "It is clear that inactivating some reactions can force other reactions to be active. We want to better understand the cell's spontaneous shutdown of parts so we can induce it ourselves."

The research team also found that when a cell is perturbed (when there is a change in the nutrients available or a gene is shut down), the number of biochemical reactions it uses increases immediately, putting it in a sub-optimal state. The cell seems lost for a while, but then it adapts to the new conditions. The number of reactions decreases, and the cell returns to an optimal state.

"A reaction becomes inactive and triggers a cascade that makes other reactions inactive until you have several hundreds or even thousands of inactive reactions," said Motter. "This is the network analogue of sculpting: in order for the desired behavior to manifest itself, specific parts of the systems have to be suppressed. In this analogy, the expression of a whole-cell objective would not be possible were it not for the pattern shaped by the absent or inactive parts in the bulk of the cellular network."

"Why do organisms have reactions they don't use? Presumably so they have the flexibility to adapt to different conditions. One optimization situation will engage a certain set of reactions, while another situation will require a different set. It remains to be demonstrated, however, whether different conditions alone can justify the presence of all available reactions. The fact that this question is yet to be answered makes the entire problem even more attractive," Motter said.

Motter and his team used computational results to re-interpret and explain specific recent experimental results. First they gathered extensive experimental information on the metabolic networks of four different single-celled organisms: three bacteria (H. pylori, S. aureus and E. coli) and yeast (S. cerevisiae). Then the researchers built general quantitative models of the organisms that allowed them to predict cellular behavior. With those models, the researchers conducted mathematical analyses and computer experiments, simulating the organism and its metabolic function under optimal and non-optimal conditions.

They observed that for all four organisms in a typical non-optimal state, all utilizable reactions in the metabolic network, with a few exceptions, were active. In contrast, when the four organisms were growing at their optimal rate, each of them spontaneously silenced a large number of metabolic reactions. The number of active reactions, around 300, was the same for all four, despite differences in the size and complexity of each organism's genome and metabolic network. And the number stayed around 300 for a variety of quite different optimization scenarios.

"Mathematical abstraction of the problem suggests that spontaneous shutdown may not be limited to metabolic networks," said Nishikawa, who led the mathematical part of the effort. "What appears to be essential for this phenomenon is that a complex network that is under constraints and locally in balance is 'trying' to optimize its function. There are other important systems, like transportation networks, where the same type of analyses could be useful."

Northwestern University

---

---

	Multiple Organisms (Sector Guard) by Devine Destinies Drahali has lived her life as a freak, a woman who was far more than one of the guys. Her strength was limitless, but it doomed her to a life alone until the day the Sector Guard recruiter arrived and offered her a chance to be his partner and possibly more. Remar suffered the same fate on his home world with his body able to split into multiple incarnations of the original. Meeting a woman who was petite, adorable and could snap him in two would have frightened a lesser man, but he could be more than she could handle any time he wished.
	Restoration of the Human Organism through Concentration on Numbers by Grigori Grabovoi (Author) Grigori Grabovoi is the author of the teaching "Deliverance and Harmonious Development," which has received acclaim through official documents of the United Nations Organization (UNO). He is a respected clairvoyant, healer and specialist in energy informatics. He was honored by the Russian Academy of Sciences with the silver medal of the Nobel Prize Award winner I. P. Pavlov for his "furthering of medicine and public health."Grigori Grabovoi is also an award winner of the International Academy of Sciences' competition on the topic "Nature and Society." He was distinguished with the Peter the Great medal for his contributions to the "revival of the science and economy of Russia." This book presents the method of improving conditions of health through concentrating on seven, eight and...
	The Life and Behavior of Living Organisms: A General Theory by Elliott Jaques (Author) Jaques presents a totally new general theoretical foundation for understanding the individual and social behavior of all living organisms. In contrast to existing theories of behavior which are static, Jaques has succeeded in breaking through to a truly dynamic orientation. This breakthrough, resulted from his fundamental research into work organizations that led to the realization that the difference between inanimate processes and all living behavior, is that all living behavior is composed of intentional goal-directed work.This continuous work entails the use of judgment in choosing goals and in making the decisions necessary to get to these goals. This work process is the same in all living organisms, including humans. It is an ineffable process of the total organism, inaccessible to...
	Behavior of Organisms by B. F. Skinner (Author)
	Behavior Of The Lower Organisms (1906) by Herbert Spencer Jennings (Author) This book is a facsimile reprint and may contain imperfections such as marks, notations, marginalia and flawed pages.
	Same Cell Organism (Yaoi) by Sumomo Yumeka (Author) Nakagawa and Yokota are two boys very much in love with each other. Yokota is more open with his feelings, but Nakagawa is easily embarrassed of public displays of affection. Though they may be outwardly different, their feelings for each other are the same - their connection is such that they liken themselves to Do-Seibutu (Same-Cell Organisms).
	Animal Physiology: From Genes to Organisms by Lauralee Sherwood (Author), Hillar Klandorf (Author), Paul Yancey (Author) Keep up with today's rapid advances in the biological sciences with ANIMAL PHYSIOLOGY: FROM GENES TO ORGANISMS 2E with CourseMate! With coverage of animal species that will be relevant to your animal-related career, this biology text provides you with the tools you need to succeed. Boxes found throughout the text such as Molecular Biology and Genomics, Beyond the Basics, Challenges and Controversies, Unanswered Questions, and A Closer Look at Adaptation give you examples of cutting-edge research and help you see how what you are learning applies to the real world. Check Your Understanding questions after each major section help you review the main ideas as you read. Each chapter then ends with a Chapter Summary, a set of Review, Synthesize, and Analyze questions, and a list of Suggested...
	The Rainbow and the Worm: The Physics of Organisms by Mae-Wan Ho (Author) This unusual book is a serious, in-depth enquiry into Schrodinger's question, "What is Life?" and at the same time, a celebration of life itself. It takes the reader on a voyage of discovery through many areas of contemporary physics from non-equilibrium thermodynamics to quantum optics, all necessary to illuminate the problem of life. In the process, the reader is treated to a rare and exquisite view of the organism, gaining novel insights, not only into the physics, but also "the poetry and meaning of being alive". It is intended for all who love the subject.
	Marine Fungi: And Fungal-Like Organisms (Marine and Freshwater Botany) by E. B. Gareth Jones (Editor), Ka-lai Pang (Editor)
	The Art of Genes: How Organisms Make Themselves by Enrico Coen (Author) Over the past twenty years there has been a revolution in biology--for the first time scientists have been able to unravel the details of how organisms make themselves. The mechanisms by which a fertilized egg develops into an adult can now be grasped in a way that was unimaginable a few decades ago. The Art of Genes is the first account of these exciting new findings, and of their broader significance in how we view ourselves. Through a highly original synthesis of sciece and art, Enrico Coen vividly describes this revolution in our understanding of how plants and animals develop. Drawing on a wide range of material--from flowers growing petals instead of sex organs, and flies that develop an extra pair of wings, to works of art by Leonardo and Magritte--he explains in lively...