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 Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>