Nobel Laureate: Peter D. Mitchell

The Nobel Prize in Chemistry 1978

"for his contribution to the understanding of biological energy transfer through the formulation of the chemiosmotic theory"

Peter D. Mitchell (1920-1992) received the Nobel Prize in 1978 for developing the Chemiosmotic Theory to explain ATP synthesis resulting from membrane-associated electron transport [Ubiquinone and the Proton Pump].

Mitchell is the last of the gentleman scientists. He first proposed the chemiosmotic principle in a 1961 Nature article while he was at the University of Edinburgh. Shortly after that, ill health forced him to move to Cornwall where he renovated an old manor house and converted it into a research laboratory. From then on, he and his research colleague, Jennifer Moyle, continued to work on the chemiosmotic theory while being funded by his private research foundation. [Peter Mitchell: Wikipedia]

The Chemiosmotic Theory was controversial in 1978 and it still has not been fully integrated into some biochemistry textbooks in spite of the fact that it is now proven. The main reason for the resistance is that it overthrows much of traditional biochemistry and introduces a new way of thinking. It is a good example of a "paradigm shift" in biology.

Because he was such a private, and eccentric, scientist there are very few photos of Peter Mitchell or his research laboratory at Glynn House . The best description of him is in his biography Wandering in the Gardens of the Mind: Peter Mitchell and the Making of Glynn by John Prebble, and Bruce Weber. A Nature review by E.C. Slater [Metabolic Gardening] gives some of the flavor and mentions some of the controversy.

Many scientists believe that the Chemiosmotic Theory was the second greatest contribution to biology in the 20th century (after the discovery of the structure of DNA). The case is strong, I think they're right.

The IDiots Understand the War in Iraq

 
DaveScot didn't like the short speech by Senator Jim Webb. Apparently Webb just doesn't get it about Iraq. According to DaveScot, there's a really good reason for being in Iraq [[Off Topic] Senator Jim Webb: Clueless.

Did you know that the real reason is to train the marines?

Here’s the deal Jim. In order to have an effective force in fighting guerilla and urban wars in Arab countries we need actual combat veterans seasoned in that type of warfare leading the unseasoned troops. Use your head, Jim. Now we have an effective force led by NCOs who know how to survive urban and guerilla wars in Arab countries. And Bush managed to build that force without losing 58,000 American lives as were sacrificed in Vietnam but rather limited the losses to 3,000. Use your head for something other than a place to put your hat, Jim. We needed a veteran ground combat force for the Middle Eastern theater. Now we have one. Now what happened to Russia in Afghanistan won’t happen to us.

Clueless.

I can't help but notice some glaring deficiencies in current military training. There are no veterans with experience in colder climates like those we find in Canada. There's also a lack of experience in the European theater—almost all the veterans from World War II have retired. And let's not forget China or India. Nobody in the Marines has ever fought in China or India.

Maybe the USA should start a war in one of those theaters in order to get some veterans?

What Is a Species? John Wilkins Knows

 
As part of the ongoing basic concepts posts, John Wilkins has described Species. John is one of the world's leading authorities on this topic so you can be sure to learn something if you jump over to Evolving Thoughts.

For those of you that don't want to learn about all the various definitions of species here's the bottom line from John ....

So, after all that, what is a species? I think, and this is very much my own opinion, that there is no ....

How to Fix NIH and NSF

 
I recently commented on the funding crisis in Canada. Less than 20% of grants will be funded in the latest CIHR competition. Canadian scientists are trying to see what needs to be done to fix the problem.

There's a similar problem in the USA. At the 2007 Science Blogging Conference we received a flyer from Geoff Davis and Peter Fiske asking people to go to their blog and get involved in the discussion about how to fix NIH and NSF. Here's the site: [Zerhouni for a Day: A challenge].

So far the main suggestions under discussion are to limit the size of grants and to cut back on funding interdisciplinary centers. Both suggestions are worth serious consideration.

Ubiquinone and the Proton Pump

Yesterday's molecule was ubiquinone, also known as coenzyme Q or just plain "Q." Ubiquinone is a lipid soluble cofactor that accepts and donates electrons in oxidation-reduction reactions. These are reactions in which electrons are transferred from one molecule (oxidation) and accepted by another (reduction).

Ubiquinone is confined to lipid membranes where it diffuses laterally. It is synthesized in reactions catalyzed by membrane-bound enzymes. Bacteria contain a structurally similar molecule called menaquinone and photosynthetic organisms have plastoquinone.

All of these quinones play a role in pumping proteins across a membrane in order to create a proton gradient that's used to make ATP. If you understand how this works then you can understand how life first arose 3.5 billion years ago.
Quinones can carry up to two electrons per molecule and they are added one-at-a-time in the reaction shown below.

The reason why ubiquinone is so important is because the ring structure stabilizes the negatively charged semiquinone anion allowing for the addition of another electron to create ubiquinol (QH₂). Note that when two electrons are taken up, two protons (H⁺) are added to neutralize the negative charge. In the reverse reaction (ubiquinol to ubiquinone: bottom to top) two protons are released when the electrons are given up.

The key to understanding the importance of ubiquinone is recognizing that protons can be taken up from one side of the membrane during the reduction of ubiquinone and they can be released on the other side of the membrane when ubiquinol is oxidized in the reverse reaction.

The enzymes responsible for this differential uptake and release are part of the membrane-associated electron transport chain found in mitochondria and in the membranes of bacteria. There are several different reactions that take place as shown in the simple schematic diagram below.

The red line traces the path of electrons released from a molecule called NADH. The electrons pass through three different membrane complexes called complex I, complex III, and complex IV. At each step, protons are pumped across the membrane. In complex IV the electrons are passed to oxygen (O₂) to make water. This final step is why you need oxygen to live.

We are mostly interested in the middle complex (complex III) because that's the one found in all species. It also takes part in photosynthesis, which is a similar process for producing a proton gradient.

The protons accumulate in the intermembrane space between the outer and inner membranes of mitochondria and bacteria. The complexes are located in the inner membrane. (The outer membrane isn't shown in the diagram.) Because there's a higher concentration of protons in the intermembrane space compared to inside the cell, there's pressure to return protons down the concentration gradient to restore the balance. This pressure is called the protonmotive force. It's used to drive ATP synthesis by coupling the transport of protons to the phosphorylation of ADP. ATP is the main energy currency in the cell. It can be used to make other molecules or cause muscles to contract etc.

The idea that electron transport is mainly used to create a proton gradient which is then used up in the synthesis of ATP is known as the Chemiosmotic Theory. It was championed in the 1960's by Peter Mitchell (see tomorrow's Nobel Laureate).

The role of quinone in complex III is complicated. Here's a schematic (left) showing the uptake of protons (H⁺) from the cytoplasmic side (bottom) to form QH₂ and their release on the other side when QH₂ is converted back to Q. This complicated set of reactions is known as the Q cycle and it is responsible for the generation of protonmotive force in all species. Since the protonmotive force is what drives ATP synthesis, this makes the Q cycle one of the most important reactions in biochemistry.

The structure of complex III has been solved. In addition to being one of the most important enzymes, it is also one of the most beautiful. You can easily see the two b heme groups that form the catalytic sites for oxidation and reduction of QH₂ and Q. The iron-sulfur center (Fe-S) helps in the transport of electrons to heme c₁ and eventually to cytochrome c.

This is such a fabulous molecule that I put it on the cover of my biochemistry book.

Students often wonder how the earliest forms of life created energy before the invention of photosynthesis. Once you understand the Chemiosmotic Theory, it isn't difficult to see how this worked 3.5 billion years ago. All you need is a source of energetic electrons to drive the reduction of quinone. In the presence of a cytochrome complex, like complex III, you'll get a protonmotive force generated by the Q cycle. This will power ATP synthesis.

Here's a simplified version of how it's done in chemoautotrophic bacteria that can use hydrogen as an energy source. There are many other possible sources of energy, such as H₂S or NH₄⁺. They are obvious candidates for the kinds of energy production that was common when life first began.

Teaching Ethics in Science: Science v Technology

Janet Stemwedel of Adventures in Ethics and Science has posted a response to my questions about teaching "ethics" in science courses. My original posting is [Ethical Issues in Science] and Janet's response is [Teaching about ethics and other sources of controversy in science class].

When we met at the 2007 North Carolina Science Blogging Conference, Janet said she was going to try and kick-start a debate. That's why I took the picture.

There are several different issues, so in order to keep the discussion focused, I'm going to limit myself to only one topic per posting. This one's about the relationship between science and technology and where "ethics" fits in.

Religion Is Losing, According to Ken Ham

 
Okay, so Ken Ham isn't a very reliable source of information. He's about as kooky as you can get when it comes to science and religion. The only things he has going for him is that he's Australian and he's not in jail.

Ken Ham is worried about the evil atheists and the influence they might have on Christian youth. Over at Answers in Genesis he's published a warning against The New Atheists. Can you guess who they might be? I thought so ....

Ham has an interesting take on the issue. He says,

It prompts me to ask: “Why are atheists now getting so much publicity and gaining ground? What’s happened in the culture to allow this?” As we’ve been saying for years, there’s been a change in this culture—at a foundation level. Generations have been indoctrinated by the secular education system and media to build their thinking on human reason, not the Word of God. And at the base of this is the creation/evolution issue.

Evolutionary indoctrination has produced generations (even in the church) who doubt the Bible. Barna Research discovered that of teenagers today who call themselves born-again Christians, only 9% believe there is such a thing as absolute truth. These young people are ripe for “secular evangelists” like Dawkins and Harris.

Who knew? Rationalism is winning over superstition? Is it time to break out the champagne?

But that's not all. There are serious consequences. If the evil atheists win the hearts and minds of our children then dreadful things could happen. But surely this will never happen ... surely rationalism will never win? Ken Ham isn't so sure,

Some people might say to me, “But there’s no way Americans will go for atheism. Most people believe in God, even if they don’t take the Bible seriously as AiG does.” Think back to the 1950s. What if someone back then said to you, “Beware, the homosexual movement is on the march—if we don’t do something, ‘gay’ marriages will be legalized across the country.” Almost all of us at that time would have said that there’s no way Americans would ever accept this. Most people believe that marriage is one man for one woman, so, no, this will never happen in America.But as you know, it has happened—and continues to happen!

Ohmygod. Not only is rationalism making inroads but tolerance as well. Religion is surely doomed. What will Ken Ham do? Stay tuned—I'm sure he has a plan to restore superstition and bigotry.

What Is "Systems Biology?"

It's an interesting question. One of our departments here at the University of Toronto just renamed itself Cell and Systems Biology so you'd think they would know what "systems biology" is, wouldn't you?

Well, they don't. And neither do I. And neither, as it turns out, does Michael White over at Adaptive Complexity. Read his posting: Is Systems Biology Teaching Us Anything New?. Here's a teaser,

What I find most exciting about basic molecular biology today is the prospect of building a quantitative understanding of how a cell works. Many other scientists are excited about this as well, leading to the current popularity of what's being called 'systems biology.' The idea is that maybe we can understand the design principles behind a cellular process - how the behavior of a cell emerges from all of those detailed physical interactions among proteins, nucleic acids and other components of the cell. If that sounds vague to you, well, that's because it is vague. It's a nice sentiment, but I think biologists still have a hard time defining just what it is we want to learn.

More Comet McNaught

 
Phill Plait of Bad Astronomy has another photo of comet McNaught [Incredible Comet McNaught photo] This is one of those (few) times when I wish I lived in the Southern Hemisphere!

Monday's Molecule #10

 
Name this molecule. You must be specific. We need the correct common name.

This is an easy one for everyone who has ever taken biochemistry. This compound is the substrate for one of the most important reactions in living cells—a reaction that powers every living organism. The enzyme that catalyzes this reaction gets my vote for the most important enzyme in the known universe.

We'll discuss what this molecule does after you've been given a chance to identify it.

Comments will be blocked for 24 hours. Comments are now permitted.

Mendel's Garden #10

 
Mendel's Garden is a blog carnival devoted to genetics. The latest version (#10) has been posted on Neurotopia 2.0 [Mendel's Garden].

There are lots of interesting articles. I like Alex Palazzo'z execellent summary of work that shows how A silent mutation affects pain perception?. An article from Sunil on lactose intolerance reveals some new information about the origin of mutations causing lactose tolerance.

For me, the most exciting news is the inclusion of two articles from Sandwalk. This is the first time any of my postings have been included in a blog carnival. Maybe this blogging thingy isn't so bad after all!

Denny Doherty Dies

 
Dennis Doherty (Denny) of The Mamas & The Papas is dead [Doherty from Mamas and Papas dies].

Denny was born in Halifax, Nova Scotia, Canada on November 29, 1940. He lived in Mississauga, Ontario, Canada, a city just west of Toronto.

Other members of the original group included Cass Elliot, who died in 1974, John Phillips, who died in 2001, and Michelle Phillips.

California dreaming on such a winter's day.

In Defense of Sam Harris

 
Jason Rosenhouse comments on the criticism of Sam Harris and on Josh Rosenau's take on the issue [Rosenau on Harris].

Here's a quote from Jason. I wish I had said this!

I find this all very frustrating. People like Harris point to specific, irrational fact claims made by certain religious traditions, establishes the harm that comes to society when large numbers of people believe those claims, and encourages people to think a bit more critically about religious beliefs. He is so militant about the subject that you know what he does? He writes books about it. He speaks publicly about it. And he tries to persuade people with nothing more formidable than rational argumentation.

For his trouble he is criticized for being extreme and intolerant. He is branded a fundamentalist. He is lectured for taking clearly stated and widely-held religious beliefs seriously, when everyone knows that real religion is all nuance and metaphor and paradoxically inexpressible cravings. He is told to shut up lest some ignoramus on the local school board hear what he is saying. He is told that he is the one sowing social discord, unlike all those religious folks who are perfectly happy to live together in peace and not engage each other on theological matters.

Teaching Science

 


I'm at a session on Teaching Science hosted by Adnaan Wasey of The Online NewsHour(PBS). There's a lot of provocative stuff. I'll have to post more later on 'cause I need to listen and pay attention.

Janet D. Stemwedel

 
I'm sitting in a lecture theater at the 2007 North Carolina Science Blogging Conference. Right now Janet Stemwedel of Adventures in Ethics and Science is talking about how to be a blogging scientist. The title of her session is "Adventures in Science Blogging: Conversations we need to have and how blogging can help us have them."



Good communication skills are essential but there are many traditional ways of communicating. So, why blog? Because blog conversations happen on a short timescale so there's instant feedback and debate. And the record of this conversation is permanent.

Blogs give us the opportunity to respond quickly to recently published papers and newspaper articles.