Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Primitive yeast yields secrets of human cholesterol and drug metabolism

By first probing the way primitive yeast make cholesterol, a team of scientists has discovered a long-sought protein whose human counterpart controls cholesterol production and potentially drug metabolism.

The collaborative study by investigators at Johns Hopkins University School of Medicine, Vanderbilt University, Indiana University and Eli Lilly Co., was published in the February issue of Cell Metabolism.

“Dap1 controls the activity of a clinically important class of enzymes required for cholesterol synthesis and drug metabolism,” says Peter Espenshade, Ph.D., assistant professor of cell biology at Johns Hopkins. “We’re excited because although we originally identified this protein in yeast, humans not only have the same protein, but it works the same way.”

The search for Dap1 began with the hunt for factors that influence the actions of a large family of enzymes called cytochrome P450. These enzymes control many life-sustaining chemical reactions in humans and other animals.

... more about:
»Dap1 »Espenshade »P450 »cholesterol »metabolism

Happily, Espenshade says, yeast have only two P450 enzymes, and both play roles in making cholesterol, narrowing down the territory for their search and giving them a telltale marker (the cholesterol) to track.

Reasoning that whatever controls the P450s likely would be turned on and off at roughly the same time as the P450 enzymes themselves, the researchers found that Dap1 does just that in the yeast cell.

To figure out what Dap1 does, Espenshade and colleagues genetically altered yeast cells to lack Dap1. Those cells predictably were unable to make cholesterol and instead contained a build-up of cholesterol precursors.

The research team then tracked Dap1’s counterpart in humans by looking for similar proteins in a computer database and repeated their experiments in human kidney cells engineered to lack the human version of Dap1. As in yeast, the altered human cells accumulated cholesterol precursors and died because cholesterol is essential for cell survival.

To show that Dap1 directly works with P450s and not through some other biochemical steps, Espenshade’s team tested the ability of human Dap1 protein to bind to four of the 57 known human P450 enzymes, essentially challenging Dap1 to bind to P450s that perform totally different functions in different cells as a way to see how far-reaching its control might be.

Dap1 locked on to all four P450s, including one required for clearing half of all known drugs from the body, another involved in making bile and one required for making natural steroid hormones in the adrenal glands.

“Collectively, our experiments suggest that Dap1 acts as a common regulator of cytochrome P450s in mammals,” says Espenshade.

Because Dap1 affects one particular P450 responsible for drug metabolism, Espenshade suspects that genetic variations in the genetic blueprint coding for Dap1 may provide clues to how and why different people react differently to certain drugs.

“Understanding the molecular underpinnings of so-called pharmacogenetic variation will have a big impact on the future of medicine,” he says.

The research was funded by the National Institutes of Health, American Heart Association and Burroughs Wellcome Fund.

Authors on the paper are Adam Hughes and Espenshade of Hopkins; David Powell and Andrew Link of Vanderbilt University School of Medicine; Martin Bard of Indiana University-Purdue University Indianapolis; James Eckstein and Robert Barbuch of Eli Lilly and Company.

Audrey Huang | EurekAlert!
Further information:

Further reports about: Dap1 Espenshade P450 cholesterol metabolism

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Novel mechanisms of action discovered for the skin cancer medication Imiquimod

21.10.2016 | Life Sciences

Second research flight into zero gravity

21.10.2016 | Life Sciences

How Does Friendly Fire Happen in the Pancreas?

21.10.2016 | Life Sciences

More VideoLinks >>>