Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Simulating human metabolism to find new diets to new drugs

30.01.2007
Computerized model will give researchers a new way to hunt for better treatments for hundreds of human metabolic disorders

Bioengineering researchers at UC San Diego have painstakingly assembled a virtual human metabolic network that will give researchers a new way to hunt for better treatments for hundreds of human metabolic disorders, from diabetes to high levels of cholesterol in the blood. This first-of-its-kind metabolic network builds on the sequencing of the human genome and contains more than 3,300 known human biochemical transformations that have been documented during 50 years of research worldwide.

In a report in the Proceedings of the National Academy of Sciences (PNAS) made available on the journal's website on Jan. 29, the UCSD researchers led by Bernhard Ø Palsson, a professor of bioengineering in the Jacobs School of Engineering, unveiled the BiGG (biochemically, genetically, and genomically structured) database as the end product of this phase of the research project.

Each person's metabolism, which represents the conversion of food sources into energy and the assembly of molecules, is determined by genetics, environment, and nutrition. In a demonstration of the power and flexibility of the BiGG database, the UCSD researchers conducted 288 simulations, including the synthesis of testosterone and estrogen, as well as the metabolism of dietary fat. In every case, the behavior of the model matched the published performance of human cells in defined conditions.

... more about:
»cholesterol »metabolic »metabolism »scientists

Researchers can use the computationally based database to quickly discover the effects on a given cell type of changing the performance of any of the 3,300 known human metabolic reactions operating in that cell. The tool is designed to help scientists explore hundreds of human disorders in the metabolism of amino acids, carbohydrates, lipids, minerals, and other molecules. It also is intended to be used in the future to study metabolic variations between people as a way to individually tailor diet for weight control.

Studying the metabolism of cholesterol is another potential application. Cholesterol is a lipid that is incorporated into all cell membranes. An estimated 105 million adults in the United States have total blood cholesterol values of 200 milligrams per deciliter (mg/dl) and higher, and of these about 36.6 million have levels of 240 mg/dl or more, according to the American Heart Association. Such high cholesterol levels are associated with an elevated risk of heart disease.

More than two dozen biochemical reactions in human cells are needed to make cholesterol. Cholesterol-lowering drugs called statins affect just one of those reactions, reducing the synthesis of cholesterol as if they were pinching a garden hose, slowing the flow of cholesterol through it. However, metabolic pathways are actually labyrinths of interconnected garden hoses with complicated flow patterns.

"Pinching off one part of the labyrinth can have a good effect, but it can also have unexpected consequences, or even no effect because of redundancy built into metabolic systems," Palsson said. "The new tool we've created allows scientists to tinker with a virtual metabolic system in ways that were, until now, impossible, and to test the modeling predictions in real cells."

Each type of cell in the human body utilizes only a fraction of all 3,300 metabolic reactions, and scientists can create in silico any type of cell, from a heart cell to a red blood cell, with its particular complement of metabolic enzymes, and adjust their genetic or other properties to compute the cell's behavior.

"We can analyze abnormal metabolism at the root cause of diseases such as hemolytic anemia, which can result from a deficiency in metabolic reactions," said Neema Jamshidi, an MD/Ph. D. student at UCSD and co-author of the paper. "We can study both the causes and consequences of this and other diseases, which may lead to novel insights about how new drugs might be designed to treat them."

After tabulating all reliable metabolic information about human cells, the team employed mathematical tools traditionally used in signal processing and operations research to identify a cell's most influential metabolic components in key metabolic states. "This approach confirmed in a mathematically rigorous way what cell biologists already understand to be true: cells use compartmentalization to coordinate their metabolism," Jamshidi said. "Our technique provides scientists with a new way to investigate the role of compartmentalization in metabolism."

The reconstructed metabolic network is based on the human genome sequence. Palsson's team of six researchers manually analyzed 1,500 key books, review papers, and legacy scientific reports published over the past 50 years. The team used strict quality control criteria accepted by the scientific community to assemble the network piece by metabolic piece during more than a year of intense work.

"This accomplishment was made possible by the Human Genome Project, and its scope and utility will grow over time," Palsson said. Some parts of human metabolism require additional research, and that information, when obtained, will be added to the model as part of the project's next phase.

Rex Graham | EurekAlert!
Further information:
http://www.ucsd.edu

Further reports about: cholesterol metabolic metabolism scientists

More articles from Life Sciences:

nachricht Switch-in-a-cell electrifies life
18.12.2018 | Rice University

nachricht Plant biologists identify mechanism behind transition from insect to wind pollination
18.12.2018 | University of Toronto

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Data storage using individual molecules

Researchers from the University of Basel have reported a new method that allows the physical state of just a few atoms or molecules within a network to be controlled. It is based on the spontaneous self-organization of molecules into extensive networks with pores about one nanometer in size. In the journal ‘small’, the physicists reported on their investigations, which could be of particular importance for the development of new storage devices.

Around the world, researchers are attempting to shrink data storage devices to achieve as large a storage capacity in as small a space as possible. In almost...

Im Focus: Data use draining your battery? Tiny device to speed up memory while also saving power

The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.

Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

Pressure tuned magnetism paves the way for novel electronic devices

18.12.2018 | Materials Sciences

New type of low-energy nanolaser that shines in all directions

18.12.2018 | Physics and Astronomy

NASA research reveals Saturn is losing its rings at 'worst-case-scenario' rate

18.12.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>