Human Anticoagulant Genes

 
One of the most important factors in anticoagulation is antithrombin III [Inhibiting Blood Clots: Anticoagulants]. The official name of this protein is serpin peptidase inhibitor and gene for antithrombin III is called SERPINC1 [GeneID=462]. The gene is located on chromosome 1 at q23-q25.1.

Deficiencies in antithrombin III cause thrombosis, or excess clotting. Dozens of different alleles are known. The defective proteins show a variety of effects including reduced binding to heparan sulfate, reduced binding to thrombin, and decreased stability [OMIM 107300]. In most cases the affected individuals contain only one copy of the mutant allele suggesting that both copies must be active for effective anticoagulant activity.

The other anticoagulant pathway requires thrombomodulin plus protein C and protein S. The gene for thrombomodulin is called THRM [GeneID=7056] and it is found on chromosome 20 at p11.2.

Mutations in THRM are associated with mild thrombosis and increased risk of myocardial infarction (heart attacks). People with this susceptibility are heterozygous for the mutant allele. Most alleles that have a physiological phenotype are recessive lethals resulting in late fetal deaths (spontaneous abortion). The defect is associated with the formation of excessive blood clots at the region where placental blood and maternal blood vessels are in close contact [OMIM 188040].

The gene for protein C is PROC [GeneID=5624] on chromosome 2 at q13-q14.

Deficiencies in protein C cause congenital thrombotic disease or thrombphilia (due to PC deficiency). The type patient ("propositus") and his family are described on the Online Mendelian Inheritance in Man entry for PROC [OMIM 176860].

Their propositus was a 22-year-old Caucasian male with recurrent thrombophlebitis complicated by pulmonary embolism. His 56-year-old father had thrombophlebitis with pulmonary embolism following a minor leg injury at age 24, a cerebrovascular accident at age 43, and a myocardial infarction at age 45. A paternal uncle had thrombophlebitis and recurrent pulmonary emboli dating from age 20. The paternal grandfather died abruptly at age 45. He had sustained a leg injury in a fall from a horse. While he was confined to bed, pulmonary infiltrates developed. These resolved, but on his first day out of bed he collapsed and died after taking a few steps. The paternal great-grandfather died unexpectedly of a cerebrovascular accident at age 61. The propositus, his father, and his paternal uncle showed levels of plasma protein C antigen (determined immunologically by the Laurell rocket technique) 38 to 49% of normal. Clinically unaffected members of the kindred had normal levels.

There are at least 25 known variants of PROC causing increased risk of thrombosis and heat attacks.

The gene for protein S is called PROS1 [GeneID=5627], located at the centromere of chromosome 3 (3p11.1-q11.2). Deficiencies in protein S produce symptoms very similar to those desribed for protein C deficiencies. As is the case with PROC mutants, PROS1 mutant alleles are dominant although the penetrance is less than 100%. What this means is that some people who are heterozygous don’t show any increased risk of thrombosis while others do. This suggests there are other factors that are required for thrombosis [OMIM 176880].

Blogger's Code of Conduct?

 
Tim O'Reilly is concerned about "civility" on blogs so he proposes a Blogger's Code of Conduct. Part of the code requires censoring comments and not allowing anonymous comments. I can't aggree to that. There are other things about the code that I disagree with.

If you follow the code you're supposed to put this sheriff's badge on your blog. I'm not going to follow the code and even if I were, the idea of advertising it with a sheriff's badge is offensive. It makes you look like a policeman.

If you're not going to follow the Blogger's Code of Conduct, this is what you're supposed to put on your blog.

This is an open, uncensored forum. We are not responsible for the comments of any poster, and when discussions get heated, crude language, insults and other "off color" comments may be encountered. Participate in this site at your own risk.

That's exactly the message I want you to hear. The only thing I censor is spam.

Nisbet & Mooney Reveal Their True Colors

As it turns out, this isn't about about framing at all. It's about religion. Here's an excerpt from an article published by Matthew C. Nisbet and Chris Mooney in tomorrow's Washington Post [Thanks for the Facts. Now Sell Them.].

If the defenders of evolution wanted to give their creationist adversaries a boost, it's hard to see how they could do better than Richard Dawkins, the famed Oxford scientist who had a bestseller with "The God Delusion." Dawkins, who rose to fame with his lucid expositions of evolution in such books as "The Selfish Gene," has never gone easy on religion. But recently he has ramped up his atheist message, further mixing his defense of evolution with his attack on belief.

Leave aside for a moment the validity of Dawkins's arguments against religion. The fact remains: The public cannot be expected to differentiate between his advocacy of evolution and his atheism. More than 80 percent of Americans believe in God, after all, and many fear that teaching evolution in our schools could undermine the belief system they consider the foundation of morality (and perhaps even civilization itself). Dawkins not only reinforces and validates such fears -- baseless though they may be -- but lends them an exclamation point.

So now we see what "framing" is all about. It's about conforming to the Nisbet & Mooney view of how we should combat superstition. According to them, Dawkins is bad, bad, bad.

Forget about the fact that Dawkins has done more to change the climate of the debate than Nisbet & Mooney have ever done with their appeasement policy. That dosen't matter. If you're a fan of "framing" then you've got to modify your opinion so you never disagree with anyone.

Well, phooey on that. No wonder "framing" has such a bad name.

We agree with Dawkins on evolution and admire his books, so we don't enjoy singling him out. But he stands as a particularly stark example of scientists' failure to explain hot-button issues, such as global warming and evolution, to a wary public.

Hmmm ... so scientists have failed to explain global warming and evolution to the general public? Well, silly them. They made the terrible mistake of speaking the truth, just like Richard Dawkins.

As we've seen during the framing debates on various blogs, Nisbet & Mooney seem to be incapable of making the distinction between explaining science and what you do with that knowledge. Evolutionists have done a good job of explaining evolution. If Nisbet & Mooney don't think this is true then I challenge them to come up with a better way of describing the science of evolutionary biology.

What they're upset about is the fact that a segment of the population doesn't buy the scientific explanation. That's true, but it doesn't matter how well you explain it to those people, they still won't accept it. They won't accept it even it's economically beneficial and leads to medical advances.

Why won't they accept it? Because it's against their religion. How do we change their minds? Part of the solution is to show them that their religion is false if it conflicts with science. This doesn't have anything to do with explaining the facts of science. It has to do with fighting superstition and anti-science attitudes.

Scientists excel at research; creating knowledge is their forte. But presenting this knowledge to the public is something else altogether. It's here that scientists and their allies are stumbling in our information-overloaded society -- even as scientific information itself is being yanked to center stage in high-profile debates.

Scientists have traditionally communicated with the rest of us by inundating the public with facts; but data dumps often don't work.

Wait a minute. Nisbet & Mooney are spinning so fast here it's hard to keep up. They start by criticizing Dawkins for promoting his opinion on religion and now they're switching to criticism of scientists who inundate the public with data dumps. Did they forget that this is the same Richard Dawkins who's sold several hundred thousand books like The Blind Watchmaker? That's a data dump? What about The Ancestor's Tale? Another data dump?

People generally make up their minds by studying more subtle, less rational factors. In 2000 Americans didn't pore over explanations of President Bush's policies; they asked whether he was the kind of guy they wanted to have a beer with.

So Richard Dawkins should concentrate on projecting the same image as George Bush, Jerry Flawell, or Ronald Regan? Matt, Chris, please tell me this is satirical comedy. You can't be serious.

So in today's America, like it or not, those seeking a broader public acceptance of science must rethink their strategies for conveying knowledge. Especially on divisive issues, scientists should package their research to resonate with specific segments of the public. Data dumping -- about, say, the technical details of embryology -- is dull and off-putting to most people. And the Dawkins-inspired "science vs. religion" way of viewing things alienates those with strong religious convictions. Do scientists really have to portray their knowledge as a threat to the public's beliefs? Can't science and religion just get along? A "science and religion coexistence" message -- conveyed in Sunday sermons by church leaders -- might better convince even many devout Christians that evolution is no real threat to their faith.

Oops. You guys haven't been listening, have you? Dawkins thinks that religion is the enemy (so do I). What you're suggesting isn't framing, it's surrender. You want Dawkins to give up his fight entirely and form an alliance with the very people he is opposing. Time for a reality check. You are so far off base, you're not even in the game.

Paul Zachary "PZ" Myers, a biology professor at the University of Minnesota at Morris, wrote on his blog, Pharyngula, that if he took our advice, "I'd end up giving fluff talks that play up economic advantages and how evolution contributes to medicine . . . and I'd never talk about mechanisms and evidence again. That sounds like a formula for disaster to me -- it turns scientists into guys with suits who have opinions, and puts us in competition with lawyers and bureaucrats in the media." Myers also accused us of appeasing religion.

Yet he misses the point. There will always be a small audience of science enthusiasts who have a deep interest in the "mechanisms and evidence" about evolution, just as there will always be an audience for criticism of religion. But these messages are unlikely to reach a wider public, and even if they do they will probably be ignored or, in the case of atheistic attacks on religion, backfire.

Someone's missing the point here and it sure ain't PZ. After decades of appeasement in America we have a situation where it's the only Western industrialized country in the world objecting to the teaching of evolution. What do Nisbet & Mooney propose to do about it? More of the same, that's what.

What is Dawkins doing about it? Pointing out that there's a hippo in the room. In the past six months since the publication of The God Delusion, we've made more progress than the Nisbet's & Mooney's of this world made in decades. The very fact that the appeasers have been forced to defend their failed strategy is proof of that.

More proof can be seen on television, newspapers, and magazines. All of a sudden people are talking about atheists and asking questions about religion. (Incidentally, Mooney could have gained a lot of credibility with me if he'd mentioned that PZ Myers is a columnist who writes for SEED magazine as well as being a blogger.)

We're not saying scientists and their allies should "spin" information; doing that would only harm their credibility. But discussing issues in new ways and with new messengers can be accomplished without distorting the underlying science. Good communication is by its very nature informative rather than misleading. Making complicated issues personally meaningful will activate public support much more effectively than blinding people with science.

I know spin when I see it and I see it clearly in the Nisbet & Mooney articles.

I wish they'd get their story straight. Are they complaining about how we scientists teach science or are they complaining about our opinions on other issues such as the influence of religion or what we should do about global warming? Who knows?

Oh, and by the way, who are the "new messengers" and what are Nisbet & Mooney going to do with the old ones? Do they honestly believe that their silly arguments are going to shut up Richard Dawkins and PZ Myers and all the rest of us who disagree with Nisbet & Mooney? Like that's going to happen.

One thing is clear. No matter how much you know about framing this isn't a question of whether you should be aware of the literature and the field. I mention this because many bloggers have criticised me for not being an expert on "framing." This isn't about framing. This is a straightforward disagreement over an important issue—is religion a problem? Nisbet & Mooney say no and that's why they're opposed to Dawkins. The fact that they couch this in terms of proper "framing" is intellectually dishonest. They're trying to "frame" this as a debate over who knows the most about "framing." Can you say "spin?"

The Demise of Scientific American

Yesterday one of my colleagues delivered a lecture on the cracking of the genetic code. I ended up discussing it with a student during the afternoon. That was an exciting time back in the early 1960's and as a teenager I followed the new biology in the pages of Scientific American. All the big names had articles in Scientific American.

Later on as a graduate student, a postdoc, and a young faculty member, I still looked forward to reading the monthly issue of Scientific American for accurate summaries of what was going on in science. But something happened in the 1990's. I started to see articles by scientists I'd never heard of even though they were writing on areas close to my interests. Furthermore, the quality of the articles was way below the standards set in previous decades. Often the authors were clearly promoting their own work and downplaying or ignoring the work of others. I started to lose confidence in Scientific American because I recognized that in my own areas of expertise the articles were no better than what you find in the tabloid science magazines. I assume this is true for all other disciplines as well.

I've criticized some of these articles in previous postings. For example, an article by Gil Ast on The Alternate Genome makes silly statements about basic molecular biology [Facts and Myths Concerning the Historical Estimates of the Number of Genes in the Human Genome]. Also see [Junk DNA: Scientific American Gets It Wrong (again)] and [The Hypocrisy of Scientific American].

[Duesberg has] proposed the hypothesis that the various American/European AIDS diseases are brought on by the long-term consumption of recreational drugs and/or AZT itself, which is prescribed to prevent or treat AIDS.
... from Peter Duesberg's website
April 14, 2007Imagine my lack of surprise when I picked up the latest issue and noticed that Peter Duesberg was the author of one of the feature articles. The editors know full well that this will provoke controversy so here's what they say in their editorial.

Even mentioning the name Peter Duesberg inflames strong feelings, both pro and con. After gaining fame in 1970 as the virologist who first identified a cancer-causing gene, in the 1980s he became the leading scientific torchbearer for the so-called AIDS dissidents who dispute that HIV causes the immunodeficiency disorder. To the dissidents, Duesberg is Galileo, oppressed for proclaiming scientific truth against biomedical dogma. A far larger number of AIDS activists, physicians and researchers, however, think Duesberg has become a crank who refuses to accept abundant proof that he is wrong. To them, he is at best a nuisance and at worst a source of dangerous disinformation on public health.

Readers may therefore be shocked to see Duesberg as an author in this month's issue. He is not here because we have misgivings about the HIV-AIDS link. Rather Duesberg has also developed a novel theory about the origins of cancer, one that supposes a derangement of the chromosomes, rather than of individual genes, is the spark that ignites malignant changes in cells. That concept is still on the fringe of cancer research, but laboratories are investigating it seriously. Thus, as wrong as Duesberg surely is about HIV, there is at least a chance that he is significantly right about cancer. We consider the case worthy of bringing to your attention.

Now let's unpack that opinion and put it in a different perspective to see where it takes us.

When it comes to AIDS, Peter Duesberg is a kook. He has consistently ignored scientific evidence in order to promote himself and his losing cause. In the face of overwhelming evidence that HIV causes AIDS he has steadfastly maintained a contrary position.

It's okay to take a minority position in science. We all do that from time to time. It's how science advances. However, there is such a thing as scientific integrity and scientific honesty. When your favorite theory goes against all scientific evidence you have two choices. You give up your theory or you stop being a credible scientist. Duesberg has chosen the second option.

There may be a chance that Duesberg is right about his new cancer theory but that's not the point. He has stopped being a scientist and he should not be given a platform in any magazine that pretends to be scientific. Once you lose your scientific credibility you have lost it forever. We don't reward such people by continuing to take them seriously as long as they avoid the one topic where their lack of integrity is known.

There are plenty of credible scientists out there who could write about cancer. The fact that Scientific American has chosen to put it's reputation behind Duesberg is just one more example of the demise of a good journal. The fact that the editors knew exactly what they were doing is not mark in their favor. They don't get bonus points for doing something wrong with their eyes wide open.

I will now put Scientific American in the same class as kooks like Duesberg. It does not deserve respect.

Jesse Cook

 
We just got back from seeing Jesse Cook. If you don't live in the Toronto area you'll just have to wait until he goes on tour in two weeks.

Testing the Macaque Genome

 
We've already been looking at the macaque genome for several months but now that the genome paper is being published I thought some of you might be interested in how the preliminary data stacks up to what we expect.

I'm interested in a family of gene known as the HSP70 gene family. The genes encode the major cellular chaperone that's responsible for correct protein folding. HSP70 is the most highly conserved gene known [Evolution of the HSP70 Gene Family].

We know how many genes there are in mammalian genomes so we can search the macaque genome at Rhesus Macaque Genome Resources to see if the expected genes are present. Here's the result.

HSPA1A: not present, probably due to incomplete sequence or annotation

HSPA1B: correct gene/protein

HSPA1L: correct gene/protein + one incorrect isoform that's really a splicing artifact

HSPA2: not present, probably due to incomplete genome or annotation

HSPA5/BiP: correct gene/protein + one incorrect alternatively spliced isoform that's really an artifact

HSPA8: one single correct gene/protein

HSP9B/mtHSP70: correct gene/protein + three incorrect isoforms generated by EST artifacts

That's not too bad for an initial draft sequence. Two genes are missing and so are several pseudogenes. I assume they'll turn up later when the genome sequence is being finished. Most of the splicing artifacts have been ignored by the annotators but a few have slipped through. They'll be deleted later on when the annotators are informed that the isoforms don't exist.

All in all, this is much better than most genome sequences at this stage. It's a bit better than the chimp genome but still a long way from the quality of the human genome. The mouse genome is almost as good as the human genome. Keep in mind that dozens of labs have been working on the human genome annotation for over six years since the sequence was first published. The cow, dog, frog and several fish genomes are in much worse shape and the chicken and sea urchin genomes are practically useless.

Horse, opossum, rat, pig, rabbit, cat, sheep, tree shrew, guinea pig, hedgehog, elephant, and platypus genomes are still at the assembly stage [Ensemble Genome Browser].

Do You Ever Wonder Why We Call them IDiots?

 
Someone named Granville Sewell has just posted a message on Uncommon Descent [Is ID Really Rooted in Science?]. He says,

Given that the most spectacular documented successes of natural selection are: changing the color of the peppered moth and the length of the beak of the Galapagos Finch, and the development of resistance to antibiotics by bacteria, and that even these trivial examples are now all in dispute, and that no competing natural explanation for evolution has ever been taken seriously by more than a small band of scientists, where is the “overwhelming” evidence that the development of life is due to natural (unintelligent) causes alone?

Hmmm ... there are only three spectacular documented examples of natural selection and all three "trivial" examples are disputed. I didn't know that. Has anyone told the textbook writers?

Natural selection is the only game in town according to Granville Sewell. No other explanations have been take seriously by more than a "small band of scientists." I didn't know that either. The textook writers need to be informed. There are entire chapers that have to be purged.

It seem no matter how much information we supply to the IDiots they refuse to listen. I know for a fact that Dembski and O'Leary have been told about other explanations. I have records of them both agreeing that there's more to evolution than just natural selection. I have written confirmation that they understand the concept of random genetic drift and why it's so incredibly important in molecular evolution.

So, let's sit back and see how long it takes them to correct their colleague. I'm gonna hold my breath 'cause it won't be long. Dembski and O'Leary are honorable people, aren't they?

Technology reveals 'lock and key' proteins behind diseases

 
A University of Toronto press release [here] announces a paper that's just been published in Molecular Cell [Paumi et al. 2007].

Paumi, C.M., Menendez, J., Arnoldo, A., Engels, E., Iyer, K.R., Thaminy, S., Georgiev, O., Barral, Y., Michaelis, S., and Stagljar, I. (2007) Mapping Protein-Protein Interactions for the Yeast ABC Transporter Ycf1p by Integrated Split-Ubiquitin Membrane Yeast Two-Hybrid Analysis. Molecular Cell 26:15-25.

One of the lead authors is my friend Igor Stagljar (that's him in the picture). The study is a collaboration between him and Susan Michaelis' group at Johns Hopkins in Baltimore MD (USA). It's a pretty decent press release without too much hype. I just wish there was more emphasis on basic biochemistry and less on possible applications in medicine. The paper describes a new technique called "Integrated Split-Ubiquitin Yeast Two-Hybrid Analysis" or iMYTH—a variant of MYTH technology. The paper has nothing to do with medicine.

The idea is to identify proteins that interact with membrane bound proteins. There are many membrane receptors that have been identified in the human genome on the basis of their similarity to known receptors. Their functions are unknown and one way to discover what they do is to detect other, hopefully known, proteins that bind to the receptors. The MYTH technology has been used to identify these interactions since it was first developed by Igor almost ten years ago. The modification in this paper is to integrate the "bait" construct into the yeast genome thus improving the sensitivity of detection (see Figure 1).

This is a proof of principle paper using a yeast ABC transporter that's being characterized by the Michaelis lab. Paumi et al. were able to identify six proteins that interact with the transporter, including Tus1P, a well-characterized guanine nucleotide exchange factor (GEF).

The exciting thing about this technique is that Igor has just introduced it into our Advanced Biochemistry Lab for undergraduates [BCH471Y]. The students are completing the final discussion day today. They identified a number of different proteins from a human brain library that interact with a human membrane receptor. One of them was a protein that had escaped detection when the experiments were first done in the Stadljar lab.

Bad Luck on Friday the 13th

 
Friday's Urban Legend: FALSE

Having a morbid fear of Friday the 13th—paraskevidekatriaphobics—is one of the most widespread superstitious beliefs in western industrialized nations. Believe it or not, there are many people who refuse to leave their house on Friday the 13th because they fear that bad luck will befall them if they venture outside. (Apparently, the bad luck doesn't find them in their homes.)

Personally, I like the attitude of the "eccentric" (rational?) men in the photo.

Members of the Eccentric Club of London at their annual Friday the 13th lunch in 1936 – surrounded by objects that are connected with superstitions. Picture: Getty Images [Unlucky roots of Friday the 13th].

There is no evidence to support the irrational fear of Friday the 13th, with the single exception of a study published 14 years ago in the British Medical Journal [Is Friday the 13th bad for your health?]. That study showed an increase in accidents on Friday the 13th compared to Friday the 6th.

According to scholars, the fear of Friday the 13th is a recent invention. There is no mention of it before 1900 [Why Friday the 13th Is Unlucky]. It seems that people simply combined a fear of the number 13—triskaidekaphobia—with an obscure dead of Fridays. Nobody knows for sure why the number 13 is considered unlucky but there are several popular myths. The most common are a Norse myth about having 13 people at dinner and a Christian myth about the Last Supper.

There is no significant historical record documenting a widespread irrational fear of Fridays although there are plenty of minor examples of Friday avoidance. Some people thought it was bad luck to be married on a Friday or to set sail on a ship. In Christian cultures the day is associated with the fact that Jesus was crucified on a Friday and Friday is the day that Adam was tempted by Eve to eat the forbidden fruit.

In Canada, bikers celebrate Friday the 13th by congregating at Port Dover on the shores of Lake Erie for a few days of partying—a tradition that's been going on for 26 years [PD13].

(While searching for information on Friday the 13th I stumbled upon this Greenpeace site [Friday the 13th]. It's a perfect example of why I have stopped supporting Greenpeace after many years of donating to them. I will not support an organization that uses that kind of scare tactic to make a case against nuclear power. It's about as low as you can go. This is what I'm reminded of when I think of "framing." Perhaps the supporters of framing could explain why I'm mistaken; if, indeed, I'm mistaken.)

Bad Luck for Men

 
Today is Friday the 13th and the bad news for men is a report that women may have discovered how to have babies without us [The prospect of all-female conception]. All the babies will be girls.

Fortunately, Steve Palter is on to it over at docinthemachine [Babies Without Men: Creating Sperm From A Woman’s Bone Marrow]. He's a fertility specialist and he reviews the science behind the story. As it turns out, pathenogenesis may not work. Imprinting may save us (temporarily) from a fate worse than death.

It all started when we let them vote. Our great-grandfathers knew it would come to this eventually.

Inhibiting Blood Clots: Anticoagulants

 
There are several naturally occurring blood clot inhibitors. The most important is antithrombin. As the name implies, antithrombin blocks the activity of thrombin and this prevents the formation of fibrin and clotting networks. It makes sense that blood clotting has to be terminated because otherwise it would grow and block the vein cutting off blood supply.

Antithrombin III, the main antithrombin activity, is a protein that binds to thrombin in the presence of an oligosaccharide called heparin. Heparin is a glycosaminoglycan (GAG) which means that it’s formed by stringing together amino sugars (glycosamines). There are seven different kins of GAG’s in humans and heparin is one of them. The repeat unit in heparin is a sulfated glucosamine plus a sulfated iduronic acid residue [Monday’s Molecule 320].

The heparin oligosaccharide is bound to a very specific protein to form heparin proteoglycan. The physiologically important oligosaccharide is called heparan sulfate. It is found on the surface of normal endothelial cells and it is this molecule that binds antithrombin III.

The combination of antithrobin III-heparin+thrombin blocks processing of fibrinogen and prevents clotting. This is why patients are treated with heparin to prevent blood clotting or to dissolve blood clots that have formed during pulmonary embolisms, strokes, or clotting in leg veins. Heparin can also be used to coat medical equipment to prevent clotting on exposed surfaces. Heparin is an anticoagulant.

A different inhibitory mechanism is initiated when thrombin binds to a membrane protein called thrombomodulin. Thrombomodulin is a glycoprotein [Glycoproteins] found on the surface of normal endothelial cells.

The thrombin:thrombomodulin complex activates Protein C, which combines with Protein S to form a protease. Activated Protein C (APC) degrades Factors Va and VIIIa. These are the two factors required for activation of Factor X in extrinsic and intrinsic activation respectively [Blood Clotting: Intrinsic Activity, Blood Clotting: Extrinsic Activity and Platelet Activation]. Thus, degradation of these factors prevents further activation of prothrombin and clotting activity ceases.

Nobel Laureate: Fritz Lipmann

 

The Nobel Prize in Physiology or Medicine 1953.



Fritz Albert Lipmann (1899-1986): "for his discovery of co-enzyme A and its importance for intermediary metabolism"

Fritz Lipmann won the Nobel Prize in 1953 for his discovery of the cofactor Coenzyme A (CoA). Initially Coenzyme A was found to be the cofactor that bound acetyl groups for oxidation by the citric acid cycle. (Also known as the Krebs cycle. Hans Krebs shared the Nobel Prize with Lipmann in 1953 [Hans Krebs].) Here's how Lipmann's discovery is described in the presentation speech.

It is necessary to introduce compounds from the outside into the Krebs cycle in order to keep it in operation, because theoretically speaking the integral components are not used up in the process. The principal incorporation takes place through Lipmann's 2-carbon compound. It had been generally assumed that this compound was closely related to acetic acid. It was known that large amounts of acetic acid are formed in the metabolism of the cell. This acid possesses two carbon atoms and could fit well into the mechanism of the Krebs cycle. It seemed quite certain that the 2-carbon compound was acetic acid, but that it was active in some unknown form. Lipmann maintained for several years that acetyl phosphate, a compound formed from acetic acid and phosphoric acid was the active principle and he defended this idea against a growing scepticism of his colleagues. Just when most biochemists became convinced that this compound would not fit into the mechanism of the Krebs cycle, and were ready to abandon the whole idea, Lipmann announced his discovery of coenzyme A. Now suddenly everything fitted perfectly - the last notch of a combination lock fell into its place.

Coenzyme A is a compound with a rather small molecule, which, when united with the enzyme-protein, acquires the property of binding acetic acid. Acetic acid is normally quite unreactive but when bound in this way it becomes labile and reactive and represents the previously mystical 2-carbon compound which combines with a 4-carbon compound to form citric acid. A new way for the transmission of energy in the cell was demonstrated by this discovery.

We now know that Coenzyme A plays a role in several other biochemical reactions, including one of the reactions of the citric acid cycle where succinyl-CoA is a key intermediate. It also plays a role in fatty acid synthesis (via malonyl-CoA) and in fatty acid degradation (via acetoacetyl-CoA).


Lipmann's name is associated with one of the most spectacular cases of scientific fraud. In the early 1960's a postdoctoral fellow in Lipmann's lab managed to fake a lot of data and he published several scientific papers with Lipmann. All of the data, including the notebooks, were elaborately constructed to look real. One of my colleagues, Byron Lane, (now retired) was given the unenviable task of uncovering the fraud when he was working in Lipmann's lab.

[Lipmann photo from the National Library of Medicine]

The Tangled Bank #77

 
The 77th edition of The Tangled Bank is up at Aetiology. Thanks to Tara Smith.

T. Ryan Gregory on the Sandwalk

 
Gregory is the man behind the genome size database at the University of Guelph, Ontario (Canada). I stole this picture from [A nod to (and from) the Sandwalk] at Genomicron.



I'm happy to post any other pictures of people on the Sandwalk. Just send them to me as an email attachment.

We'd be better off without Religion

 
Here's an interesting guestion. On Tuesday, March 27th 2,000 people showed up at Westminster Central Hall in London to hear Richard Dawkins, Christopher Hitchens, and AC Grayling debate Baroness Julia Neuberger, Roger Scruton, and Nigel Spivey on the subject "We'd be better of without religion." [Articles of Faith, We'd be better off without Religion]. I'm practically certain that you could never get 2,000 people out to such an event in Toronto. How about other cities; New York, Morris, San Francisco, Houston?

Assuming that the answer is no, what's different about London and how can we copy it?

Isn't it strange that the "aggressive atheists" are getting so much positive attention? From what you hear on some of the blogs you'd think that the crowd would be throwing rocks rather than listening attentively.