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Monday, November 12, 2007
Monday's Molecule Copycat
One of my offspring—who shall remain nameless—has decided to make fun of my Monday's Molecule feature. Go to her blog and tell her to behave herself [The Monday Molecule - Belgium Version].
Monday's Molecule #51
Today's molecule may seem very simple but your task is to give it a complete IUPAC name as well as the common name. You also have to identify the origin of the common name. Pay close attention to the structure before you venture a guess.
There's a direct connection between this molecule and Wednesday's Nobel Laureate(s).
The reward goes to the person who correctly identifies the molecule and the Nobel Laureate(s). Previous winners are ineligible for one month from the time they first collected the prize. There are two ineligible candidates for this week's reward. The prize is a free lunch at the Faculty Club.
Send your guess to Sandwalk (sandwalk(at)bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule, the origin of the common name, and the Nobel Laureate(s). Correct responses will be posted tomorrow along with the time that the message was received on my server. I may select multiple winners if several people get it right.
UPDATE: We have a winner! Satoris guessed that the molecule was squalene [2,6,10,15,19,23-Hexamethyl-2,6,10,14,18,22-tetracosahexaene] and the name squalene is derived from squalus meaning "shark." Squalene was first isolated from shark liver. The word squalus comes from the Latin word squalus. It originally meant any marine fish.
Several people got this part right but Sartoris was the only person to guess the correct Nobel Laureate. I was thinking of the person who worked out the detailed pathway for biosynthesis of squalene. You will find out tomorrow.
Reading Level Comparison
BarryA has posted the following comment on Uncommon Descent [Reading Level Comparison].
Thanks to one of our commenters for pointing out this website that calculates the reading level of blogs. Just for fun I inserted UD and it came back “High School,” which means that the general discussion at this blog is at a high school level. I then inserted Pandas Thumb and it came back “Elementary School.”This seems curious so I tried it myself. Here's the result for "www.uncommondescent.com."
Make of this what you will.
The Salem Conjecture
The Salem Conjecture was proposed by Bruce Salem on the newsgroup talk.origins [The Salem Conjecture]. Here's how he described it on Sept. 5, 1996.
Joshua Rosenau discusses the possibility that the hard version of the Salem Conjecture might be correct and this explains the soft version [The Salem Hypothesis explained!]. Read the comments.
My position is not that most creationists are engineers or even that engineering predisposes one to Creationism. In fact, most engineers are not Creationists and more well-educated people are less predisposed to Creationism, the points the statistics in the study bear out. My position was that of those Creationists who presented themselves with professional credentials, or with training that they wished to represent as giving them competence to be critics of Evolution while offering Creationism as the alternative, a significant number turned out to be engineers.This should not be confused with the "hard" version of the Salem Conjecture (Hypothesis), which says that engineers are more likely to be creationists. Both versions are described in the Wikipedia entry [Salem Hypothesis].
Joshua Rosenau discusses the possibility that the hard version of the Salem Conjecture might be correct and this explains the soft version [The Salem Hypothesis explained!]. Read the comments.
[Photo Credit: I pretty sure this is a photograph of Bruce Salem.]
Sunday, November 11, 2007
Beyond Belief II: Enlightenment 2.0
By all accounts this year's Beyond Belief symposium in San Diego was a lot less exciting than last year's [Beyond Belief II: Enlightenment 2.0]. Perhaps it's because Richard Dawkins wasn't there. On the other hand, PZ Myers was there [Speakers].
There's a short review of the highlights in this week's issue of New Scientist [Does God have a place in a rational world?]. From the sounds of it, the lack of clear-headed atheists led to some very sloppy thinking.
The first firebrand is lobbed into the audience by Edward Slingerland, an expert on ancient Chinese thought and human cognition at the University of British Columbia in Vancouver, Canada. "Religion is not going away," he announced. Even those of us who fancy ourselves rationalists and scientists, he said, rely on moral values - a set of distinctly unscientific beliefs.Oops. I've got news for you, Prof. Slingerland, you can't count yourself as a rationalist if you think that morality requires religion. And you can't lay claim to being a scientist if you think that moral values are unscientific. That's two strikes.
Where, for instance, does our conviction that human rights are universal come from? "Humans' rights to me are as mysterious as the holy trinity," he told the audience at the Salk Institute for Biological Studies. "You can't do a CT scan to show where humans' rights are, you can't cut someone open and show us their human rights," he pointed out. "It's not an empirical thing, it's just something we strongly believe. It's a purely metaphysical entity."Strike three. It's a good thing Dawkins wasn't there or this kind of sloppy thinking would have been exposed.
Who said we all have a conviction that human rights are universal? Not me, that's for sure. I can't think of a single "human right" that qualifies. Furthermore, those human rights that we generally agree upon in the 21st century are not mysterious to me. They're mostly common sense designed to maximize our ability to live in groups. It's an empirical thing—and we're still working on the best compromises between absolute rights and qualified ones.
The mood at this follow-up conference was different. Last year's event was something of an "atheist love fest" said some, who urged a more wide-ranging discourse this time round. While all present agreed that rational, evidence-based thinking should always be the basis of how we live our lives, it was also conceded that people are irrational by nature, and that faith, religion, culture and emotion must also be recognised as part of the human condition. Even the title of this year's meeting, "Beyond Belief II: Enlightenment 2.0", suggested the need for revision, reform and a little more tolerance.Hmmm ... I guess I can go along with that. I've known for some years that people are attracted to irrationality and superstition—we call it religion. We tolerate those who ignore rationality and evidence-based thinking but that doesn't mean we shouldn't criticize those who think that way, right? Tolerance doesn't mean the same as acceptance, does it?
There's one comment in that paragraph that puzzles me. Is it true that people are irrational by nature and it's part of human nature? My observations suggest the opposite. It seems to me that most humans strive to be rational as opposed to irrational. They may get confused from time to time about what is rational and what isn't but over the centuries rationalism tends to win out over superstition. Why do we have to concede that superstition is here to stay because it's pat of the human condition. That doesn't make sense.
Such was the message from evolutionary biologist David Sloan Wilson of Binghamton University, New York. He suggested that humans' religious beliefs may have evolved over time, thanks to the advantages they conferred as a sort of social glue holding together groups that developed them.Hmmm ... if irrationality and superstition are hard-wired into our brains then how come it's so easy for many of us to escape from this sort of thinking?
Wilson was not saying religion is good or bad, simply that it has evolved to be hard-wired into our brains, and therefore cannot be ignored. "Adaptation is the gold standard against which reality must be judged," he said. "The unpredictability and unknown nature of our environment may mean that factual knowledge isn't as useful as the behaviours we have evolved to deal with this world."
I often wonder whether people like Wilson have thought seriously about what they're saying. Does he imagine a time when primitive humans didn't have religion because it hadn't yet evolved? How did those groups manage to survive? I wonder what went on in their brains when they couldn't think about supernatural explanations?
Or did the religion allele(s) arise before the hominid lineage? Have chimps got religion and that's what what makes them stick together? (Instead of sex.) What about gorillas? Who do they worship? Howler monkeys? Meerkats?
Chemist Peter Atkins of the University of Oxford, one of the more hard-line atheists in the room, did not let this go unchallenged. He chided fellow participants for not being sufficiently proud about what science can accomplish. Given time and persistence, science will conquer all of nature's mysteries, he said.I'm glad to see there was at least one rationalist present.
So can scientific and religious world views ever be reconciled? Harris, author of The End of Faith, declared that they could not, and provided an uncompromising exposition on the evils of religion.Maybe there were more rationalists present than the author of the piece is willing to admit?
Away from the meeting, philosopher Daniel Dennett of Tufts University in Medford, Massachusetts, told New Scientist that as irrational as human minds may be, calm, firm introduction of reason into the world's classrooms could over time purge them of religion.
[PhotoCredits: Beyond Belief II: Enlightenment 2.0, Meerkats]
Saturday, November 10, 2007
With Friends Like This ....
Greta Christina has a blog called Greta Christina's Blog (naturally). She posts lots of interesting stuff about atheism and other things. Today she strayed into science and posted a video about macroevolution (see below) [Macro-evolution" Vs. "Micro-evolution": More Video Fun]. Greta introduced it with ...
First, just so everyone's clear: "Macro-evolution" and "micro-evolution" are made-up words concocted by creationists to make themselves sound scientific. Biologists don't use them. They're scientifically meaningless. They're just different stages in the evolutionary process; "macro" is just "micro" over a longer period of time.I posted this comment on her blog.
I'm afraid you have been mislead. Microevolution and macroevolution are perfectly good scientific terms and they are used by evolutionary biologists all the time.
There is legitimate scientific debate about whether macroevolution is more than just lots of microevolution or whether macroevolution encompasses mechanisms not seen in microevolution. It's the sufficiency of microevolution argument.
I happen to be one of those scientists who agree with Stephen Jay Gould that there are many levels of evolution (hierarchical theory). Thus, macroevolution cannot be sufficiently explained by lots of microevolution. There are other things going on at the higher levels [Macroevolution].
The video is very misleading because it assumes a simplistic version of macroevolution. There aren't any evolutionary biologists who believe in that kind of macroevolution. Thus, I have to conclude that the makers of the video are as ignorant of evolution as the creationists they mock.1
1The video was made by cdk007 who claims to have a Masters degree in Biology and a Ph.D. in Molecular Neuroscience.
[The science book covers pictured are:
Macroevolution: Diversity, Disparity, Contingency: Essays in Honor of Stephen Jay Gould
At the Water's Edge: Macroevolution and the Transformation of Life
Genetics, Paleontology, and Macroevolution]
The Photosynthesis Song and a Pet Peeve
Photosynthesis is a process where light energy is captured and converted to chemical energy in the form of ATP. The basic process is similar to that in membrane-associated electron transport. In both cases an energy source (light or reducing equivalents respectively) is used to create a proton gradient across a membrane. The dissipation of this gradient as protons move back into the cell drives the synthesis of ATP.
In addition to ATP, most types of photosynthesis can also be coupled to synthesis of NADPH. The chemical energy molecules derived from photosynthesis (ATP and NADPH) are used in many different biochemical pathways such as DNA synthesis, protein synthesis, fatty acid synthesis and carbohydrate synthesis.
Most photosynthetic organisms can fix carbon dioxide and make carbohydrates using ATP and NADPH [The Calvin Cycle] [Fixing Carbon: the Rubisco Reaction]. Many nonphotosynthetic organisms can do this too. In photosynthetic bacteria and photosynthetic protists this pathway uses only a small part of the chemical energy created by photosynthesis. In large plants the synthesis of carbohydrates can use up a significant portion of the ATP and NADPH generated by photosynthesis.
The fixation of CO2 and the synthesis of carbohydrates used to be called the "dark reactions" of photosynthesis back in the days when all we knew about were big plants. We didn't know anything about the biochemistry of photosynthetic bacteria or other species. Because our attention was focused on big plants, it was thought that photosynthesis was always coupled to the carbohydrate synthesis pathways. Now we know that this isn't true, so the old-fashioned equation,
is just not a valid representation of photosynthesis. The real products of photosynthesis don't even appear in the equation and, furthermore, those products are used for many different purposes inside the cell (especially in bacteria). Not only that, in some photosynthetic bacteria the electron donor isn't water but some other inorganic molecule like H2S and S2 is produced instead of oxygen. The equation is very misleading on many levels and should be abandoned.
Greg Laden has posted the video shown below and commented on the fact that the word "miracle" is used [The Photosynthesis Song ... Bad Word Choice?]. I'm much more worried about the misleading science in the video than I am about one instance of the word "miracle."
In addition to ATP, most types of photosynthesis can also be coupled to synthesis of NADPH. The chemical energy molecules derived from photosynthesis (ATP and NADPH) are used in many different biochemical pathways such as DNA synthesis, protein synthesis, fatty acid synthesis and carbohydrate synthesis.
Most photosynthetic organisms can fix carbon dioxide and make carbohydrates using ATP and NADPH [The Calvin Cycle] [Fixing Carbon: the Rubisco Reaction]. Many nonphotosynthetic organisms can do this too. In photosynthetic bacteria and photosynthetic protists this pathway uses only a small part of the chemical energy created by photosynthesis. In large plants the synthesis of carbohydrates can use up a significant portion of the ATP and NADPH generated by photosynthesis.
The fixation of CO2 and the synthesis of carbohydrates used to be called the "dark reactions" of photosynthesis back in the days when all we knew about were big plants. We didn't know anything about the biochemistry of photosynthetic bacteria or other species. Because our attention was focused on big plants, it was thought that photosynthesis was always coupled to the carbohydrate synthesis pathways. Now we know that this isn't true, so the old-fashioned equation,
is just not a valid representation of photosynthesis. The real products of photosynthesis don't even appear in the equation and, furthermore, those products are used for many different purposes inside the cell (especially in bacteria). Not only that, in some photosynthetic bacteria the electron donor isn't water but some other inorganic molecule like H2S and S2 is produced instead of oxygen. The equation is very misleading on many levels and should be abandoned.
Greg Laden has posted the video shown below and commented on the fact that the word "miracle" is used [The Photosynthesis Song ... Bad Word Choice?]. I'm much more worried about the misleading science in the video than I am about one instance of the word "miracle."
FOX News Anchor Want USA to Support Terrorism
This is really quite incredible. Brain Kilmeade is the co-host of of the Fox and Friends morning news program. He thinks the USA should support terrorists inside Iran who will set off car bombs in Tehran. The conservative right really doesn't get it, do they?
The war against Iran is coming soon to a theater near you.
[Hat Tip: Jim Lippard]
Cafe Inquiry
The Centre for Inquiry (Toronto) and the University of Toronto Secular Alliance are pleased to announce the first Cafe Inquiry. These monthly meetings will focus on topics of interested to the secular community.
The first meeting is going to be held in conjunction with a series of lectures sponsored by CFI. The speaker happens to be me, talking about Evolution as a Theory and a Fact. If you haven't had enough of me on this blog, then come out to the Centre for Inquiry on Wednesday November 28 at 7 pm or McMaster University on the evening of November 27th. The McMaster event is sponsored by the McMaster Association of Secular Humanists.
For more information see [Evolution Is a Theory and a Fact with Prof. Laurence Moran].
Friday, November 09, 2007
Supermouse
This CNN report tells us about a supermouse created by Hansen's group at Case Western Reserve University (Hakimi et al. 2007). They inserted an extra copy of the PEPCK gene into the mouse genome and drove expression of that gene in muscle cells. The mice with extra PEPCK in their muscle cells were seven times more active than normal mice. As you can see in the CNN report, they can run on a treadmill for much longer times than mice without the extra PEPCK.
I'm sure most of know about Phosphoenolpyruvate carboxykinase (PEPCK) because it's a really important enzyme. For the very few who don't know their biochemistry pathways, here's a brief lesson.
Here's a simplified overview of the main biosynthesis pathways. The important ones are gluconeogenesis (the biosynthesis of glucose) and the citric acid cycle. Various intermediates in the citric acid cycle are used for synthesis of amino acids. One of them, oxaloacetate, is the substrate for PEPCK in a reaction that converts oxaloacetate to phosphoenolpyruvate.
This is a way to use the carbon atoms of citric acid cycle intermediates in the synthesis of glucose. Under normal circumstances the intermediates in the citric acid cycle don't change very much but their concentration can increase when amino acids are degraded in the reverse of the amino acid synthesis pathways shown here.
The activity of the supermouse is explained by increases in the number of mitochondria in muscle cells and more efficient utilization of oxygen. It is not clear why an increase in PEPCK levels causes such a drastic effect. It could be due to the fact that the mammalian version of PEPCK uses GTP ...
and one of the reactions in the citric acid cycle requires GDP. This could increase flux in the citric acid cycle leading to greater synthesis of ATP in the mitochondrial membranes. (The greater the flux, the more NADH is produced, and every mole of NADH makes 2.5 moles of ATP.)
Alternatively, the increase in stamina could be due to the fact that oxaloacetate is removed from the pool of citric acid cycle intermediates and this results in increased flux since the pools don't become too large when amino acid are broken down to citric acid cycle intermediates.
Finally, increased PEPCK activity could produce more phosphoenolpyruvate which is readily converted to acetyl CoA that can be used in the synthesis of triglycerides (fatty acids) [THEME: Pyruvate Dehydrogenase]. The storage of fatty acids supplies an energy-rich source that can be used up during exercise. In normal mice, the energy is derived from glucose molecules stored as glycogen but fatty acids are better.
All these possibilities are discussed in the paper but no definite conclusions are reached. Richard Hansen has been working on this enzyme for thirty years and it's truly remarkable that we still don't have a good idea about its role in mammalian metabolism. PEPCK is found in all species and it seems clear in most species that it plays a role in the biosynthesis of glucose from fatty acids. In species other than mammals, the citric acid cycle is short-circuited by the glyoxylate pathway which provides a route for acetyl CoA to be converted to glucose. Acetyl CoA is produced when fatty acids are degraded. Mammals don't have the glyoxylate pathway enzymes.
Hakimi, P., Yang, J., Casadesus, G., Massillon, D., Tolentino-Silva, F., Nye, C.K., Cabrera, M.E., Hagen, D.R., Utter, C.B., Baghdy, Y., Johnson, D.H., Wilson, D.L., Kirwan, J.P., Kalhan, S.C. and Hanson, R.W. (2007) Overexpression of the Cytosolic Form of Phosphoenolpyruvate Carboxykinase (GTP) in Skeletal Muscle Repatterns Energy Metabolism in the Mouse. J Biol Chem. 282:32844-32855. [PubMed]
Curing Leg Cramps with a Bar of Soap
Friday's Urban Legend: ALMOST CERTAINLY FALSE
Some people, who shall remain nameless, sleep with a bar of Ivory soap in their beds. Now why in the world would anyone do this? Well, it turns out that the bar of Ivory soap prevents you from having leg cramps at night.
I kid you not. People swear by it.
After a little investigation it turns out that there are just as many people who swear that it has to be Dove soap and not Ivory soap. Then there are those who say it can be any kind of soap as long as it's not Dove. Some people say the soap has to be in its original wrapper and others say it has to be unwrapped.
The snopes.com website hedges their bets on this one since there are so many people who claim that it works [Soap Dope]. On the other hand, they do list it under "Old Wives Tales."
I'm not so hesitant. There's no possible scientific explanation that could explain how a bar of soap would prevent leg cramps. It sounds like a placebo effect, at best, and an overactive imagination, at worst.
[Photo Credit Wikkepedia]
Thursday, November 08, 2007
Best Countires for Academic Research
From TheScientist [Best countries for Academic Research].
Judging by the results for the other categories (e.g. Top 40 US Academic Institutions, Top 10 International Academic Institutions) I don't think this is a serious poll. It follows that TheScientist isn't a credible magazine.
What Is Framing?
Matt Nisbet is still puzzled over opposition to framing. He doesn't understand why some of us don't like the idea very much. Personally, I don't think it's much different than "spin."
Nisbet's latest lament is posted today [UPDATED SECTION: What is framing? [video]].
Matt, you've explained the concept as well as you can—which isn't very well as it turns out. On your website you give us some fine examples of framing [What Is Framing?]. Here they are in case anyone doesn't get it.
Matt says that scientists should engage in framing. I say they shouldn't, and it's not because I don't understand what framing is all about. These are the "successful" examples, in Matt's opinion, and he's supposed to be the expert. Why is he surprised at the opposition to framing? Why should scientists attempt to mimic these examples of misleading and highly deceptive spin?
Nisbet's latest lament is posted today [UPDATED SECTION: What is framing? [video]].
If the blog debate that ensued after publication of our article at Science showed anything, it was just how widely misunderstood the concept of framing might be. Not surprisingly, many bloggers offer strong opinions about framing and its relationship to science communication but have very little actual knowledge or expertise in the area.Yes, that must be the answer. We don't understand framing but as soon as we do we'll get right to it. Not.
Matt, you've explained the concept as well as you can—which isn't very well as it turns out. On your website you give us some fine examples of framing [What Is Framing?]. Here they are in case anyone doesn't get it.
Frame devices are used strategically in almost any policy debate. Consider just a few prominent and successful examples of such devices that have been used to alter the focus of policy:I get it. I don't want any part of that kind of "framing."
1. Republicans have used the frame device "death tax" to recast estate tax policy in populist terms and to trigger wider public concern.
2. Democrats have used the phrase "gun safety" to shift the traditional debate over "gun control" away from a focus on civil liberties and instead toward an emphasis on public health.
3. Greenpeace has used the term "frankenfood" to redefine food biotechnology in terms of unknown risks and consequences rather than the industry-promoted focus on solving world hunger.
4. Religious conservatives have relabeled the medical procedure know as "dilation and extraction" as "partial birth abortion," pushing decision-making on whether to use the procedure away from doctors and into the hands of Congress and the courts.
5. Anti-smoking advocates have promoted the term "big tobacco," a headline-friendly phrase that immediately emphasizes considerations of corporate accountability and wrongdoing.
6. Anti-evolutionists have coined the slogan "teach the controversy," which instantaneously signals their preferred interpretation that there are holes in the theory of evolution and that teaching rival explanations for life's origins is really a matter of intellectual freedom.
Matt says that scientists should engage in framing. I say they shouldn't, and it's not because I don't understand what framing is all about. These are the "successful" examples, in Matt's opinion, and he's supposed to be the expert. Why is he surprised at the opposition to framing? Why should scientists attempt to mimic these examples of misleading and highly deceptive spin?
Is framing just false spin? What may have led to this misperception is that several examples of highly effective messaging have originated from groups or individuals with special interests. While the content of some of these messages such as Greenpeace's "Frankenfood" is debatable, these messages have been more effective in reaching key audiences than many efforts that originated from the scientific community.In other words; yes, successful framing can be the same as false spin. Thanks for explaining that, Matt.
Succcinate Dehydrogenase and Evolution by Accident
Succinate dehydrogenase is one of the enyzmyes of the citric acid cycle. It catalyzes the following reaction .....
Students in my biochemistry class will recognize this as a classic oxidation-reduction reaction where succinate is oxidized to fumarate and quinone (Q) is reduced to quinol (QH2). (The green carbons are the ones originally derived from the acetyl group that starts the cycle.)
The succinate dehydrogenase complex is also complex II in membrane-associated electron transport. This is the electron transport process that's coupled to ATP formation—part of what used to be called oxidative phosphorylation or respiration. The complexes are found in the inner membranes of mitochondria in eukaryotes and the inner plasma membrane in bacteria.
Within the complex, electrons are passed from succinate to FAD and then to three different iron-sulfur ([Fe-S]) clusters and finally to a molecule of quinone (Q) bound to the active site in the membrane (Q and QH2 are only soluble in the membranes.)
The reverse reaction, where electrons flow from QH2 to fumarate is common in bacteria. It is usually catalyzed by a separate enzyme called fumarate reductase. The two complexes (succinate dehydrogenase and fumarate reductase) are very similar in structure and the various subunits of the complexes are homologous.
The structure of succinate dehydrogenase from Escherichia coli was solved at good resolution some years ago [PDB 1NEK]. It reveals the presence of a heme b group in the membrane-bound part of the complex. The binding site for QH2 is located close to the third [Fe-S] cluster near the inner side of the membrane.
The role of this heme is highly controversial. It's not present in fumarate reductase, demonstrating that it plays no role in electron transport for the reverse reaction. It seems as though the heme group might not be involved in the transfer of electrons from succinate to QH2 either but it has been difficult to rule this out.
Tran et al. (2007) have investigated the role of heme b in a paper that has just appeared in the online version of PNAS. They created mutant enzymes that could not bind the heme b molecule and examined the effect of these mutations. Mutant bacteria grew normally under conditions where the activity of succinate dehydrogenase was essential. The levels of enzyme activity of two different mutant enzymes were only 6% and 30% lower than the levels of the wild-type enzymes.
These results demonstrate that the heme b group is not required for the chemical reaction. This confirms a lot of previous work that pointed to the same conclusion. However, the mutant enzymes are less stable than the wild-type enzyme; they tend to lose activity during purification. This indicates that the heme group helps to stabilize the complex although whether this is significant in vivo remains an open question.
The result is further proof that not every feature has adaptive significance—or, at least not the significance you would normally assign. When the heme b molecule was first detected it was assumed to be involved in the chemical reaction since that's what heme groups do in most other complexes. Now we know it is not required for electron transfer but may play a small role in stabilizing the enzyme. Maybe there used to be a heme in the primitive ancestor of succinate dehydrogenase (SQR) and fumarate reductase (QFR) but it has been lost in QFR and rendered almost obsolete in SQR. Perhaps it used to be an essential component of the reaction in the ancestor enzyme or perhaps a primitive heme b enzyme that bound quinone just happened to evolve a binding site for another enzyme containing [Fe-S] clusters and succinate oxidation properties.
The more we study these molecular machines, the more we are coming to realize that the evolutionary pathway leading to their formation was somewhat haphazard and accidental. These are not cases where the final product is so well designed that a very precise series of improbable events had to happen in order for them to exist at all. Instead, proteins that may have originally served another purpose are co-opted and modified in newly evolving complexes.
Modern enzyme complexes may contain fossil evidence of their evolutionary history (e.g. heme b) that has very little to do with their current function. It's like biochemical junk.
Students in my biochemistry class will recognize this as a classic oxidation-reduction reaction where succinate is oxidized to fumarate and quinone (Q) is reduced to quinol (QH2). (The green carbons are the ones originally derived from the acetyl group that starts the cycle.)
The succinate dehydrogenase complex is also complex II in membrane-associated electron transport. This is the electron transport process that's coupled to ATP formation—part of what used to be called oxidative phosphorylation or respiration. The complexes are found in the inner membranes of mitochondria in eukaryotes and the inner plasma membrane in bacteria.
Within the complex, electrons are passed from succinate to FAD and then to three different iron-sulfur ([Fe-S]) clusters and finally to a molecule of quinone (Q) bound to the active site in the membrane (Q and QH2 are only soluble in the membranes.)
The reverse reaction, where electrons flow from QH2 to fumarate is common in bacteria. It is usually catalyzed by a separate enzyme called fumarate reductase. The two complexes (succinate dehydrogenase and fumarate reductase) are very similar in structure and the various subunits of the complexes are homologous.
The structure of succinate dehydrogenase from Escherichia coli was solved at good resolution some years ago [PDB 1NEK]. It reveals the presence of a heme b group in the membrane-bound part of the complex. The binding site for QH2 is located close to the third [Fe-S] cluster near the inner side of the membrane.
The role of this heme is highly controversial. It's not present in fumarate reductase, demonstrating that it plays no role in electron transport for the reverse reaction. It seems as though the heme group might not be involved in the transfer of electrons from succinate to QH2 either but it has been difficult to rule this out.
Tran et al. (2007) have investigated the role of heme b in a paper that has just appeared in the online version of PNAS. They created mutant enzymes that could not bind the heme b molecule and examined the effect of these mutations. Mutant bacteria grew normally under conditions where the activity of succinate dehydrogenase was essential. The levels of enzyme activity of two different mutant enzymes were only 6% and 30% lower than the levels of the wild-type enzymes.
These results demonstrate that the heme b group is not required for the chemical reaction. This confirms a lot of previous work that pointed to the same conclusion. However, the mutant enzymes are less stable than the wild-type enzyme; they tend to lose activity during purification. This indicates that the heme group helps to stabilize the complex although whether this is significant in vivo remains an open question.
The result is further proof that not every feature has adaptive significance—or, at least not the significance you would normally assign. When the heme b molecule was first detected it was assumed to be involved in the chemical reaction since that's what heme groups do in most other complexes. Now we know it is not required for electron transfer but may play a small role in stabilizing the enzyme. Maybe there used to be a heme in the primitive ancestor of succinate dehydrogenase (SQR) and fumarate reductase (QFR) but it has been lost in QFR and rendered almost obsolete in SQR. Perhaps it used to be an essential component of the reaction in the ancestor enzyme or perhaps a primitive heme b enzyme that bound quinone just happened to evolve a binding site for another enzyme containing [Fe-S] clusters and succinate oxidation properties.
The more we study these molecular machines, the more we are coming to realize that the evolutionary pathway leading to their formation was somewhat haphazard and accidental. These are not cases where the final product is so well designed that a very precise series of improbable events had to happen in order for them to exist at all. Instead, proteins that may have originally served another purpose are co-opted and modified in newly evolving complexes.
Modern enzyme complexes may contain fossil evidence of their evolutionary history (e.g. heme b) that has very little to do with their current function. It's like biochemical junk.
Tran, Q.M., Rothery, R.A., Maklashina, E., Cecchini, G. and Weiner, J.H. (2007) Escherichia coli succinate dehydrogenase variant lacking the heme b. Proc. Natl. Acad. Sci. (USA) published online November 7, 2007, 10.1073/pnas.0707732104 [PNAS]
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