Glycogen Synthesis

All cells are capable of making glucose. The pathways is called gluconeogenesis and the end product is not actually glucose but a phosphorylated intermediate called glucose-6-phosphate.

Glucose-6-phosphate (G6P) serves as the precursor for synthesis of many other compounds such as the ribose sugars needed in making DNA and RNA. The only organisms that make free glucose are multicellular organisms, such as animals, that secrete it into the circulatory system so it can be taken up and used by other cells (Glucose-6-phosphate cannot diffuse across the membrane so it's retained within cells.)

In times of plenty, G6P may not be needed in further biosynthesis reactions so cells have evolved a way of storing, or banking, excess glucose. The stored glucose molecules can then be retrieved when times get tough. Think of bacteria growing in the ocean, for example. There may be times when an abundant supply of CO₂ combined with a surplus of inorganic energy sources (e.g., H₂S) allows for synthesis of lots of G6P. These cells can store the excess G6P by making glycogen—a polymer of glucose residues.

Glycogen consists of long chains of glucose molecules joined end-to-end through their carbon atoms at the 1 and 4 positions. The chains can have many branches. Completed chains can have up to 6000 glucose residues making glycogen one of the largest molecules in living cells.

The advantage of converting G6P to glycogen is that it avoids the concentration effects of having too many small molecules floating around inside the cell. By compacting all these molecules into a single large polymer the cell is able to form large granules of stored sugar (see photo above).

The first step in the synthesis of glycogen is the conversion of glucose-6-phosphate to glucose-1-phosphate by the action of an enzyme called phosphoglucomutase. (Mutases are enzymes that rearrange functional groups, in this case moving a phosphate from the 6 position of glucose to the 1 position.) The glycogen synthesis reaction requires adding new molecules that will be connected to the chain through their #1 carbon atoms so this preliminary reaction is required in order to "activate" the right end of the glucose residue.
Glucose-1-phosphate is the "Cori ester" [Monday's Molecule #25] that was discovered by Carl Cori and Gerty Cori while they were working out this pathway [Nobel Laureates: Carl Cori and Gerty Cori].

The next step is the conversion of glucose-1-phosphate to the real activated sugar, UDP-glucose. The enzyme is UDP-glucose pyrophosphorylase and the UDP-glucose product is similar to many other compound that are activated by attaching a nucleotide. In some bacteria, the activated sugar is ADP-glucose but the enzyme is the same as that found in eukaryotes. ADP-glucose is the activated sugar in plants, as well. In plants the storage molecules are starch, not glycogen, but the difference is small (starch has fewer branches).

Glycogen synthesis is a polymerization reaction where glucose units in the form of UDP-glucose are added one at a time to a growing polysaccharide chain. The reaction is catalyzed by glycogen synthase.



[©Laurence A. Moran. Some of the text is from Principles of Biochemistry 4th ed. ©Pearson/Prentice Hall]

Mendel's Garden #14

 

Mendel's Garden #14 has been posted on Epigenetic News.

Nobel Laureate: Walther Hermann Nernst

 

The Nobel Prize in Chemistry 1920.

"in recognition of his work in thermochemistry"

Walther Hermann Nernst won the Nobel Prize in 1920 for his work in understanding the energy of reactions. The main work is summarized in the presentation speech,

Before Nernst began his actual thermochemical work in 1906, the position was as follows. Through the law of the conservation of energy, the first fundamental law of the theory of heat, it was possible on the one hand to calculate the change in the evolution of heat with the temperature. This is due to the fact that this change is equal to the difference between the specific heats of the original and the newly-formed substances, that is to say, the amount of heat required to raise their temperature from 0° to 1° C. According to van't Hoff, one could on the other hand calculate the change in chemical equilibrium, and consequently the relationship with temperature, if one knew the point of equilibrium at one given temperature as well as the heat of reaction.

The big problem, however, that of calculating the chemical affinity or the chemical equilibrium from thermochemical data, was still unsolved.

With the aid of his co-workers Nernst was able through extremely valuable experimental research to obtain a most remarkable result concerning the change in specific heats at low temperatures.

That is to say, it was shown that at relatively low temperatures specific heats begin to drop rapidly, and if extreme experimental measures such as freezing with liquid hydrogen are used to achieve temperatures approaching absolute zero, i.e. in the region of -273° C, they fall almost to zero.

This means that at these low temperatures the difference between the specific heats of various substances comes even closer to zero, and thus that the heat of reaction for solid and liquid substances practically becomes independent of temperature at very low temperatures.

Today, Nernst is known for his other contributions to thermodynamics. In biochemistry he is responsible for the Nernst equation that relates standard reduction potentials and Gibbs free energy.

The Nernst Equation

 
In standard oxidation-reduction reactions you can usually tell whether a given compound will donate or receive electrons by looking at the standard reduction potential (ΔE°ʹ) [Oxidation-Reduction Reactions]. This is a big step toward understanding how electrons flow in biochemical reactions but we would like to know more about the energy of oxidation-reduction reactions since they are the fundamental energy-producing reactions in the cell.

The standard reduction potential for the transfer of electrons from one molecular species to another is related to the standard Gibbs free energy change (ΔG°ʹ) for the oxidation-reduction reaction by the equation

where n is the number of electrons transferred and ℱ (F) is Faraday’s constant (96.48 kJ V^-1 mol^-1). ΔE°ʹ is defined as the difference in volts between the standard reduction potential of the electron-acceptor system and that of the electron-donor system. The Δ (delta) symbol indicates a change or a difference between two values.

You may recall that electrons tend to flow from half-reactions with a more negative standard reduction potential to those with a more positive one. For example, in the pyruvate dehydrogenase reaction electrons flow from pyruvate (E°' = -0.48 V) to NAD⁺ (E°' = -0.32 V). We can calculate the change in standard reduction potentials; it's equal to +0.16 V [-0.32 - (-0.48) = +0.16].

Now we can calculate a standard Gibbs free energy change (ΔG°ʹ) for the electron transfer part of the pyruvate dehydrogenase reaction. Two electrons are transferred from pyruvate to NAD⁺ so the standard Gibbs free energy change is -31 kJ mol^-1 [-2(96.48)(0.16)]. This turns out to be a significant amount of energy that could be captured by the NADH molecule but you have to keep in mind that this is a standard Gibbs free energy change and conditions inside the cell are far from standard. The biggest difference is that standard Gibbs free energy changes are computed with equal concentrations of reactants and products at a concentration of 1M—about a thousand times higher than the concentrations inside the cell where, in addition, the concentrations of reactants and products are not equal.

Fortunately, we have a way of adjusting the values of the Gibbs free energy change and the change in the standard reduction potential to account for the actual concentrations inside the cell. The standard Gibbs free energy change is related to the equilibrium constant of a reaction K_eq by the equation

Just as the actual Gibbs free energy change for a reaction is related to the standard Gibbs free energy change by this equation, an observed difference in reduction potentials (ΔE) is related to the difference in the standard reduction potentials (ΔE°') by the Nernst equation.

By combining equations for ΔG°ʹ we get
For a reaction involving the oxidation and reduction of two molecules, A and B,
the Nernst equation is
where [A_ox] is the concentration of oxidized A inside the cell. The Nernst equation tells us the actual difference in reduction potential (ΔE) and not the artificial standard change in reduction potential (ΔE°ʹ).

At 298 K (25° C), this equation reduces to
where Q represents the ratio of the actual concentrations of reduced and oxidized species. To calculate the electromotive force of a reaction under nonstandard conditions, use the Nernst equation and substitute the actual concentrations of reactants and products. Keep in mind that a positive E value indicates that an oxidation-reduction reaction will have a negative value for the standard Gibbs free energy change.

The Nernst equation is very famous but it's actually not very useful. The problem is that many of the oxidation-reduction reactions take place within an enzyme complex such as the pyruvate dehydrogenase complex. The concentrations of the reactants and products are difficult to calculate under such conditions. That's why we usually use the standard reduction potentials instead of the actual reduction potentials, keeping in mind that these are only approximations of what goes on inside the cell.

Let's see what happens when we calculate the standard Gibbs free energy change for the reaction where NADH donates electrons to oxygen. Oxygen serves as an electron sink for getting rid of excess electrons [Oxidation-Reduction Reactions].

NAD⁺ is reduced to NADH in coupled reactions where electrons are transferred from a metabolite (e.g., pyruvate) to NAD⁺. The reduced form of the coenzyme (NADH) becomes a source of electrons in other oxidation-reduction reactions. The Gibbs free energy changes associated with the overall oxidation-reduction reaction under standard conditions can be calculated from the standard reduction potentials of the two half-reactions using the equations above.

As an example, let’s consider the reaction where NADH is oxidized and molecular oxygen is reduced. This represents the available free energy change during membrane-associated electron transport. This free energy is recovered in the form of ATP synthesis.

The two half-reactions from a table of standard reduction potentials are,

and
Since the NAD⁺ half-reaction has the more negative standard reduction potential, NADH is the electron donor and oxygen is the electron acceptor. The net reaction is
and the change in standard reduction potential is

Using the equations described above we get

What this tells us is that a great deal of energy can be released when electrons are passed from NADH to oxygen provided the conditions inside the cell resemble those for the standard reduction potentials (they do). The standard Gibbs free energy change for the formation of ATP from ADP + P_i is -32 kJ mol^-1 (the actual free-energy change is greater under the conditions of the living cell, it's about -45 kJ mol^-1). This strongly suggests that the energy released during the oxidation of NADH under cellular conditions is sufficient to drive the formation of several molecules of ATP. Actual measurements reveal that the oxidation of NADH can be connected to formation of 2.5 molecules of ATP giving us confidence that the theory behind oxidation-reduction reactions is sound.

[©Laurence A. Moran. Some of the text is from Principles of Biochemistry 4th ed. ©Pearson/Prentice Hall]

A Rational Canadian Speaks Out

 
Dan Gardner wrote a column in the Ottawa Citizen [Those fanatical atheists]. He makes so much sense I'm just going to quote several paragraphs and let everyone see what every rational person should be saying. This is the effect Richard Dawkins is having and I think it's about time.

Then there's the problem on the other side -- among the atheists such as Richard Dawkins who have been labelled "fanatics." Now, it is absolutely true that Dawkins' tone is often as charming as fingernails dragged slowly down a chalkboard. But just what is the core of Dawkins' radical message?

Well, it goes something like this: If you claim that something is true, I will examine the evidence which supports your claim; if you have no evidence, I will not accept that what you say is true and I will think you a foolish and gullible person for believing it so.

That's it. That's the whole, crazy, fanatical package.

When the Pope says that a few words and some hand-waving causes a cracker to transform into the flesh of a 2,000-year-old man, Dawkins and his fellow travellers say, well, prove it. It should be simple. Swab the Host and do a DNA analysis. If you don't, we will give your claim no more respect than we give to those who say they see the future in crystal balls or bend spoons with their minds or become werewolves at each full moon.

And for this, it is Dawkins, not the Pope, who is labelled the unreasonable fanatic on par with faith-saturated madmen who sacrifice children to an invisible spirit.

This is completely contrary to how we live the rest of our lives. We demand proof of even trivial claims ("John was the main creative force behind Sergeant Pepper") and we dismiss those who make such claims without proof. We are still more demanding when claims are made on matters that are at least temporarily important ("Saddam Hussein has weapons of mass destruction" being a notorious example).

So isn't it odd that when claims are made about matters as important as the nature of existence and our place in it we suddenly drop all expectation of proof and we respect those who make and believe claims without the slightest evidence? Why is it perfectly reasonable to roll my eyes when someone makes the bald assertion that Ringo was the greatest Beatle but it is "fundamentalist" and "fanatical" to say that, absent evidence, it is absurd to believe Muhammad was not lying or hallucinating when he claimed to have long chats with God?

[Hat Tip: PZ Myers]

Oxidation-Reduction Reactions

 
Biochemical reactions are just a complicated form of organic chemistry. Living organisms have evolved enzymes that make these reactions go faster but the underlying chemistry is unchanged.

Cells are constantly having to deal with the problem of shuffling electrons and channeling them to the right place. You might be familiar with the classic fuel metabolism example of glycolysis where the breakdown of glucose to CO₂ releases electrons. When a reaction results in the loss of electrons it's called an oxidation reaction. When electrons are gained it's a reduction reaction. Oxidations and reductions always go together since electrons are passed from one molecule to another.


Loss of Electrons is Oxidation (LEO)


Gain of Electrons is Reduction (GER)


LEO says GER


Oxidation Is Loss of electrons (OIL)


Reduction Is Gain of electrons (RIG)


OIL RIG

During glycolysis, the electrons that are released have to be deposited in some sort of electron sink and expelled as waste. If a cell couldn't get rid of its electrons it would build up a huge negative charge.

Oxygen is the electron sink in mammalian fuel metabolism. A molecule of oxygen takes up electrons and combines with protons to make water. The easiest way to see this is to draw the molecules as Lewis structures showing the valence electrons (Pushing Electrons).

There are sixteen electron on each side of this equation for the reduction of molecular oxygen. Remember, reduction is a gain of electrons. This is a half-reaction, there is no corresponding oxidation that provides the electrons so this isn't a valid oxidation-reduction reaction. It just shows the reduction part.

None of the reactions of glycolysis result in the direct reduction of molecular oxygen. In all cases, the release of electrons when glucose is broken down to CO₂ is coupled to temporary electron storage in various coenzymes. We have already encountered several of these electron storage molecules such as ubiquinone, FMN & FAD, and NADPH.

We discussed a simple electron transport chain where electrons were passed from pyruvate to NAD⁺ in the pyruvate dehydrogenase reaction. This is a classic oxidation-reduction reaction.

How do we know which direction electron are going to flow? For example, if ubiquinone is reduced to ubiquinol by acquiring two electrons then where do the electrons come from? Can NADH pass electrons to ubiquinone or does ubiquinol pass its two electrons to NAD⁺? And where does FAD⁺ fit? Can it receive electrons from NADH?

The answer is related to the reduction potential of the various electron carriers. In order to understand reduction potentials we need to learn a little inorganic chemistry.

The reduction potential of a reducing agent is a measure of its thermodynamic reactivity. Reduction potential can be measured in electrochemical cells. An example of a simple inorganic oxidation-reduction reaction is the transfer of a pair of electrons from a zinc atom (Zn) to a copper ion (Cu²⁺) as shown below. When a pair of electrons is removed from zinc it leaves a zinc ion that's deficient in two negative charges (Zn²⁺). These electrons can be taken up by a copper ion (Cu²⁺) resulting in a copper atom (Cu) with no charge.

This reaction can be carried out in two separate solutions that divide the overall reaction into two half-reactions. At the zinc electrode, two electrons are given up by each zinc atom that reacts (the reducing agent). The electrons flow through a wire to the copper electrode, where they reduce Cu2+ (the oxidizing agent) to metallic copper. A salt bridge, consisting of a tube with a porous partition filled with electrolyte, preserves electrical neutrality by providing an aqueous path for the flow of nonreactive counterions between the two solutions. The flow of ions and the flow of electons are separated in an electrochemical cell. Electron flow (i.e., electric energy) can be measured using a voltmeter.
The direction of the current through the circuit in the figure indicates that Zn is more easily oxidized than Cu (i.e., Zn is a stronger reducing agent than Cu). The reading on the voltmeter represents a potential difference—the difference between the reduction potential of the reaction on the left and that on the right. The measured potential difference is the electromotive force.

It is useful to have a reference standard for measurements of reduction potentials just as in measurements of Gibbs free energy changes. For reduction potentials, the reference is not simply a set of reaction conditions but a reference half-reaction to which all other half-reactions can be compared. The reference half-reaction is the reduction of H+ to hydrogen gas (H2). The reduction potential of this half-reaction under standard conditions (E̊) is arbitrarily set at 0.0 V. The standard reduction potential of any other half-reaction is measured with an oxidation-reduction coupled reaction in which the reference half-cell contains a solution of 1M H+ and 1 atm H2(gaseous), and the sample half-cell contains 1 M each of the oxidized and reduced species of the substance whose reduction potential is to be determined. Under standard conditions for biological measurements, the hydrogen ion concentration in the sample half-cell is (pH 7.0). The voltmeter across the oxidation-reduction couple measures the electromotive force, or the difference in the reduction potential, between the reference and sample half-reactions. Since the standard reduction potential of the reference half-reaction is 0.0 V, the measured potential is that of the sample half-reaction.
The table below gives the standard reduction potentials at pH 7.0 (E̊́) of some important biological half-reactions. Electrons flow spontaneously from the more readily oxidized substance (the one with the more negative reduction potential) to the more readily reduced substance (the one with the more positive reduction potential). Therefore, more negative potentials are assigned to reaction systems that have a greater tendency to donate electrons (i.e., systems that tend to oxidize most easily).

It's important to note the direction of all these reactions is written in the form of a reduction or gain of electrons. That's not important when it comes to determining the direction of electron flow. For example, note that the reduction of acetyl-CoA to pyruvate is at the top of the list (E̊́= -0.48 V). This is the reaction catalyzed by pyruvate dehydrogenase. Electrons released by the oxidation of pyruvate will flow to any half reaction that has a higher (less negative) standard reduction potential. In this case the electrons end up in NADH (E̊́ = -0.32 V).

The reduction of oxygen is way down at the bottom of the list. That's why it's an effective electron sink for gettng rid of electrons.

Now we'd like to know something about the thermodynamics of these electron transport reactions so we can find out how much energy is available to do useful work. This will lead us to the Nobel Laureate for April 25th.

[©Laurence A. Moran. Some of the text is from Principles of Biochemistry 4th ed. ©Pearson/Prentice Hall]

Pushing Electrons

 
Biochemistry, as the name implies, is concerned with the chemistry of life. The chemistry part is mostly organic chemistry and organic chemistry is mostly about pushing electrons.

Covalent bonds are formed when the nuclei of two atoms share a pair of electrons. The "bond" is actually a cloud of electrons orbiting the two nuclei. The atoms are held together because neither one is stable without the shared electrons. The reactions in organic chemistry and biochemistry can be thought of as simple rearrangements of electrons to form new covalent bonds and break apart old ones. In this sense it's all about pushing electrons from one location to another.

The best way to think about covalent bonds is to visualize the electrons in the other shell of atoms. Those are the ones that participated in bonding. The outer shell electrons are often referred to as the valence electrons. The first shell of electrons can only hold two electrons. Hydrogen atoms have a single electron so in order to form a stable compound they have to combine with something that supplies an electron that can be shared. The simplest of these compounds is a molecule of hydrogen (H₂).

When two atoms of hydrogen combine to form H₂ both atoms succeed in filling their outer shells with two electron by sharing electrons. The shared pair of electrons is the covalent bond. The type of structures shown in the equation are called Lewis Structures. The dots represent electrons in the outer shell of the atom.

The inner electron shell can only hold two electrons but all other shells can accommodate eight electrons. The atomic number of oxygen is 8, which means that it has two electrons in the inner shell and only six in the outer shell. It needs to combine with two other atoms in order to get enough electrons to fill the outer shell.
In this example, oxygen with six electrons in the valence shell is combining with two hydrogen atoms to form water (H₂O). By sharing electrons both the hydrogen atoms and the oxygen atom will complete their outer shells of electrons—hydrogen with two electrons and oxygen with eight.

Sometimes atoms can share more than a pair of electrons. For example, when two atoms of oxygen combine to form the oxygen molecule (O₂) there are four electrons shared between the two atoms. This results in a double bond between them.
Carbon has an atomic number of 6, which means that it has two electrons in the inner shell and only four electrons in the outer shell. Carbon can combine with four other atoms to fill up its outer shell with eight electrons. This ability to combine with several different atoms is one of the reasons why carbon is such a versatile atom. The structure of ethanol (CH₃CH₂OH, left) illustrates this versatility. Note that each atom has a complete outer shell of electrons and that each carbon atom is covalently bonded to four other atoms.

Biochemical reactions are a lot more complicated but once you understand the concept of electron pushing it becomes relatively easy to make sense of the reaction mechanisms seen in textbooks. The only additional information you need is the knowledge that some atoms can carry an extra electron and this makes them a negatively charged ion (e.g., — O^-). Some stable atoms are missing an electron in their outer shell so this makes them a positively charged ion (e.g., — N⁺).

In many cases a proton (H⁺) is released from a compound leaving its electron behind. This proton has to combine with an atom that already has a pair of electrons in its outer shell (e.g., a base B:). Here's an example of the reaction mechanism for aldolase, one of the enzymes in the gluconeogenesis/glycolysis pathway.
The outline of the enzyme is shown in blue. One of the key concepts in biochemistry is that enzymes speed up reactions, in part, by supplying and storing electrons. In this case an electron withdrawing group (X) pulls electrons from oxygen and this weakens the carbon-oxygen double bond (keto group). Carbon #2, in turn, pulls an electron from carbon #3 weakening the C3-C4 bond that will be broken. (Aldolase cleaves a six-carbon compound into two three-carbon compounds as shown here. It also preforms the reverse reaction where two three-carbon compounds are combined to form a six-carbon compound.)

A basic residue in the protein (B) removes a proton from the -OH (hydroxyl) group to form a B-H covalent bond. This leaves an additional electron on the oxygen and it combines with one left on C4 to from a double bond. The red arrows show the movement of electrons in these reaction mechanisms.

The key point here is that biochemical reactions are just like those of all chemical reactions. They involve the movement of electrons to break and form covalent bonds.

Canada's Secret Spy Coin

 
According to the US Defense Department, Canada is planting coins containing secret radio transmitters on US Defense contractors travelling in Canada ['Poppy quarter' behind spy coin alert]. The coins are the 2004 commemorative quarters issued to remember those who died in Canada's wars. The coins have a red poppy in the center [In Flanders Fields].

Here's what the Associated Press article says,

WASHINGTON - An odd-looking Canadian quarter with a bright red flower was the culprit behind a false espionage warning from the Defense Department about mysterious coins with radio frequency transmitters, The Associated Press has learned.
ADVERTISEMENT

The harmless "poppy quarter" was so unfamiliar to suspicious U.S. Army contractors traveling in Canada that they filed confidential espionage accounts about them. The worried contractors described the coins as "filled with something man-made that looked like nano-technology," according to once-classified U.S. government reports and e-mails obtained by the AP.

I can see why the contractors were confused. American coins and paper money are so boring they probably thought every country had boring money.

Actually it's all a ruse to direct the contractors' attention away from the real source of the radio transmitters. They're in Tim Hortons coffee.

[Hat Tip: Mustafa Mond, FCD]

Theme: The Three Domain Hypothesis

 
This is a series of postings that describe the Three Domain Hypothesis. The Three Domain Hypothesis is the idea that life is divided into three domains—bacteria, archaebacteria, and eukaryotes—and that the archaebacteria and eukaryotes share a common ancestor. An example of this tree of life is shown on the Dept. of Energy (USA) Joint Genome Initiative website [JGI Microbial Genomes] (left).

The hypothesis was promoted by Carl Woese in the 1980's but the pure form has now been abandoned and replaced with a “net of life” concept of early evolution as shown in the figure below. This figure is taken from Ford Doolittle's Scientific American article "Uprooting the Tree of Life" (February 2000). © Scientific American




The Three Domain Hypothesis (part 1) (Nov. 17, 2006 )

The Three Domain Hypothesis (part 2) (Nov. 22, 2006)

The Three Domain Hypothesis (part 3) (Nov. 26, 2006)

The Three Domain Hypothesis (part 4) (Nov. 29, 2006)

The Three Domain Hypothesis (part 5) (Dec. 8, 2006)

The Three Domain Hypothesis (part 6) Carl Woese (Dec. 31, 2006)

Now the IDiots Don't Get Evolution (Feb. 14, 2007)

The Web of Life (March 15, 2007)

Is "Prokaryote" a Useful Term? (October 4, 2007)

Celebrating the Three Domain Hypothesis (October 18, 2007)

The Tree of Life (May 22, 2008)

Sequence Alignment (June 22, 2008)

On the Origin of Eukaryotes (December 27, 2008)

The Tree of Life (July 29, 2009)

Perspectives on the Tree of Life: Ford Doolittle (July 30, 2009)

Perspectives on the Tree of Life: Day One (July 31, 2009)

Perspectives on the Tree of Life: Day Two (August 1, 2009)

Perspectrives of the Tree of Life: Day Three (August 7, 2009)

Monday's Molecule #25

 
Name this molecule. We need the exact name since it's pretty easy to guess one of the trivial names.

As usual, there's a connection between Monday's molecule and this Wednesday's Nobel Laureate(s). This one is dead easy—at least it will seem that way once you recognize the Nobel Prize winner(s). The reward (free lunch) goes to the person who correctly identifies both the molecule and the Nobel Laureate(s). (Previous free lunch winners are ineligible for one month from the time they first won. There is only one ineligible candidate for this Wednesday's reward.)

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

Saving Bigfoot

 
Mike Lake is the Canadian member of parliament for Edmonton-Mill Woods-Beaumont. He belongs to the Conservative Party of Stephen Harper.

Lake is 38 years old and has a bachelor of commerce degree from the University of Alberta. In other words, he is a university graduate.

Lake calls for bigfoot to be protected under Canada's Species at Risk Act [Bigfoot risks extinction, says Canadian MP]. It appears that Mike Lake has been persuaded to make a fool of himself by bigfoot "researcher" Todd Standing. This should not be a surprise since all Conservative MP's have already demonstrated a certain amount of detachment from reality.

Canadians will get a kick out of another press release [Bigfoot May Gain Protection by Canadian Parliament] where Mike Lake MP is identified as a member of the Canadian Mounted Police.

[Hat Tip: fellow Canadian James Hrynyshyn]

Gene Genie #6

 
Read the sixth edition of Gene Genie at Scienceroll [Gene Genie: a Famous Blog Carnival’s Sixth Issue]. There's lots of good science but if that doesn't tempt you then go for the videos on Mendel and genetics.

My contributions are the articles on the genes for The Human Genes for the Pyruvate Dehydrogenase Complex and Noncoding DNA and Junk DNA.

What's Your Abel Number?

 
Pharmacologists at the recent Experimental Biology meeting in Washington were excited about their Abel numbers [Six degrees of pharmacology]. The Abel number represents the number of links to John J. Abel, the founder of modern pharmacology. In this case the links have to be through authors on a publication.

I wonder who we could choose for biochemistry?

They Put Nicotine in Tim Hortons Coffee

 
Friday's Urban Legend: FALSE

Have you received an email message like this one?

Are you a Non- Smoker or Against smoking all together ?

Do you ever wonder why you have to have your coffee every morning?

** TIM HORTON'S SHOCKER **

A man from Arkansas came up to Canada for a visit only to find himself in the hospital after a couple of days. Doctor's told him that he had suffered of cardiac arrest. He was allergic to Nicotine. The man did not understand why that would of happened as he does not smoke knowing full well he was allergic to Nicotine. He told the doctor that he had not done anything different while he was on vacation other than having Tim Horton's coffee. The man then went back to Tim Horton's and asked what was in their coffee. Tim Horton's refuses to divulge that information. After threatening legal action, Tim Horton's finally admitted.....

*** THERE IS NICOTINE IN TIM HORTON'S COFFEE ***

A girl I know was on the patch to quit smoking. After a couple of days she was having chest pains & was rushed to the hospital. The doctor told her that she was on a Nicotine overload. She swore up & down that she had not been smoking. SHE WAS HAVING HER COFFEE EVERY MORNING.

Now imagine a women who quits smoking because she finds out that she is pregnant, but still likes to have her Tim Horton's once in a while.

THIS IS NOT A JOKE, PLEASE PASS THIS ALONG.... YOU MIGHT SEE THIS ON THE NEWS SOON.

Another version has "them" putting MSG in the coffee instead of nicotine. That's the version that I received this week from well-meaning, but not very skeptical, friends.

As usual, snoopes.com is on the case [Nicotine Non-Fit]. There is no nicotine in Tim Hortons coffee and there's no MSG either.

I'm a "Modernist"

 

You scored as Modernist. Modernism represents the thought that science and reason are all we need to carry on. Religion is unnecessary and any sort of spirituality halts progress. You believe everything has a rational explanation. 50% of Americans share your world-view. Modernist 100% Materialist 88% Existentialist 81% Postmodernist 44% Romanticist 38% Idealist 31% Cultural Creative 25% Fundamentalist 0% What is Your World View? created with QuizFarm.com

[Hat Tip: Shalini]

USA Is Number 2 in Health Care

 
Scientific American, that paragon of science writing, has an article on health care. It reports the results of a study done by a bunch of Canadians. They compare the health care systems in the USA and Canada and discover that We're Number Two: Canada Has as Good or Better Health Care than the U.S..

According to Woolhandler, by looking at already ill patients, the researchers eliminated any Canadian lifestyle advantage and just examined the degree to which the two systems affected patient deaths. (Mortality was the one kind of data they could extract from a disparate pool of 38 papers examining everything from kidney failure to rheumatoid arthritis.)

Overall, the results favored Canadians, who were 5 percent less likely than Americans to die in the course of treatment. Some disorders, such as kidney failure, favored Canadians more strongly than Americans, whereas others, such as hip fracture, had slightly better outcomes in the U.S. than in Canada. Of the 38 studies the authors surveyed, which were winnowed down from a pool of thousands, 14 favored Canada, five the U.S., and 19 yielded mixed results.

These studies are never conclusive. There will always be people who quibble about this or that and just as you might expect there is the obligatory complaint about wait times in Canada.

The point isn't so much whether Canada is better—although it is—the point is that Americans have just got to stop pretending that they have the best health care system in the world. At the very least it's time to admit that it's "one of the best." One thing is very clear, the American system may not be the best in the world but it's sure the most expensive.

The study's authors highlight the fact that per capita spending on health care is 89 percent higher in the U.S. than in Canada. "One thing that people generally know is that the administration costs are much higher in the U.S.," Groome notes. Indeed, one study by Woolhandler published in The New England Journal of Medicine in 2003 found that 31 percent of spending on health care in the U.S. went to administrative costs, whereas Canada spent only 17 percent on the same functions.

I suspect there are many European countries with health care systems that are just as good as the one in America. I suspect that Japan, New Zealand, and Australia have good health care as well. I've never seen any data that shows that the quality of health care in America is better than everywhere else in the world. It seems to be one of those myths of American superiority that has no basis in fact. The myth prevents Americans from joining the rest of the civilized world and adopting socialized medicine.

Seven Warning Signs of Bogus Science

 
One of my readers (thanks Allyson) has directed me to an article on the Seven Warning Signs of Bogus Science. Most of them are familiar to skeptics but they deserve to be more widely publicized. Here are seven ways to recognize a kook.

1. The discoverer pitches the claim directly to the media.
2. The discoverer says that a powerful establishment is trying to suppress his or her work.
3. The scientific effect involved is always at the very limit of detection.
4. Evidence for a discovery is anecdotal.
5. The discoverer says a belief is credible because it has endured for centuries.
6. The discoverer has worked in isolation.
7. The discoverer must propose new laws of nature to explain an observation.

I'd like to add an eight criterion to this list.

8. The discoverer does not critically evaluate contrary evidence.

Science Blogs

 
The latest issue of Cell has an opinion piece on science blogs by Laura Bonetta. Laure did her homework. She interviewd many of us and distilled the results into a pretty good summary of what science blogging is all about [Scientists Enter the Blogosphere].

I'm pleased that she quoted me on the trade-off between writing a blog and the amount of time it takes away from doing other things.

Moran, at age 60, is somewhat unique among bloggers. Most bloggers, regardless of what they write about, tend to be younger. According to the Pew Internet and American Life Project more than half of all bloggers in the United States are under the age of 30. “Most of my colleagues think what I do is strange. Partly, that's because they are not into the technology. I happen to have grown up with the Internet and understand its culture,” says Moran. “I think the younger people who are blogging now are likely to be doing it when they are 60.”

The age barrier is not the only thing keeping more scientists from blogging. The biggest impediment is probably lack of time. According to most bloggers, posts can take 30 minutes to a couple of hours to research and compose. That may not seem like much, except that a critical factor for a blog's success is that posts are updated frequently, ideally at least once a day. “If I ever stop doing this, it is because of time commitment,” says Moran.

This is an important point. I don't know how some of my blogger friends can keep on posting several things every day. It takes me hours to write up a scientific posting. I just can't do it every day.

On the other hand, it takes me only a few minutes to post an opinion piece. Perhaps that's why those postings are more common, even on science blogs. Here's the conundrum. Does a science blog need to have controversial opinion pieces in order to attract enough readers to make the science postings worthwhile? I think the answer is yes.

Undegraduate Research Experience

 
The following press release appeared on EurekAlert [Students benefit from undergraduate research opportunities].

Students benefit from undergraduate research opportunities

Many pursue advanced degrees in science, technology, engineering and mathematics

Undergraduate students who participate in hands-on research are more likely to pursue advanced degrees and careers in science, technology, engineering and mathematics (STEM) fields, according to a new study.

The study's authors state that National Science Foundation (NSF) and other entities' efforts to encourage representation of underrepresented groups in STEM fields appear to be effective.

For example, students who entered 2-year colleges were as likely as those who entered 4-year colleges or universities to participate in research. And undergraduate researchers were more likely than non-researchers to pursue a doctorate.

"This study indicates that carefully designed undergraduate research experiences motivate students," said Myles Boylan, program director for NSF's Course, Curriculum and Laboratory Improvement Program in the Divisions of Undergraduate Education and Graduate Education. "Students consider their research experiences to be effective previews of doing STEM graduate work as well as good learning experiences."

Many of the talks and discussions at the recent Experimental Biology meeting in Washington focused on the value of the undergraduate research experience. There were a lot of talks noting the correlation between students who went on to graduate school and students who did an undergraduate research project. Most assumed that it was the undergraduate research experience that motivated students to apply to graduate school.

I'm a little disappointed in these claims. As a scientist, I'm well aware of the fact that a correlation does not prove a cause. In my school, the undergraduates know that you have to do an undergraduate research project in order to enhance your chances of getting into graduate school. Thus, students who are motivated to go to graduate school will choose to do an undergraduate reseach project. I'm not sure that the undergraduate research experience is what motivates students to apply to graduate school or whether it is the motivation to go to graduate school that causes students to choose an undergraduate research project.

In my experience, the undergraduate research project is a fourth (senior) year phenomenon. Usually the application to graduate school has to be sent in before Christmas and the GRE's have to be written long before that. To me this suggests that the motivation precedes the research experience but then I'm just a scientist. What do I know about these things?

Don't get me wrong, I think research experience is a wonderful thing. My concern is that its value is being hyped at the expense of other ways of acquiring knowledge and motivating students to pursue a career in science.

At the meeting, I attended ten different talks on undergraduate research. There wasn't a single talk about how to improve the teaching of basic concepts and principles in biochemistry and molecular biology. Is this a problem? You bet. Several of the speakers revealed some misunderstanding of those very concepts and principles. This leads me to suspect that they are concentrating too much on the "doing" of science and not enough on the understanding.

Where Was I Yesterday? (3)

 

Where Was I Yesterday? (2)

 

Where Was I Yesterday? (1)

 

Nobel Laureate: Christiaan Eijkman

 
 

The Nobel Prize in Physiology or Medicine 1929.



Christiaan Eijkman (1858-1930): "for his discovery of the antineuritic vitamin"



Christiaan Eijkman won the Nobel Prize in 1929 for his observations leading to the discovery of thiamine or vitamin B₁. Deficiencies of thiamine cause beriberi, a disease that was widespread in Asia before the cause was discovered by Eijkman.

The story of Christiann Eijkman is well-known to most biochemistry students. Here's the story as recounted in the Nobel Prize presentation speech.

That the fruits of civilization are not solely beneficial is shown by, inter alia, the history of the art of medicine. Not a few illnesses and diseases follow close on the heels of, and are more or less directly caused by, civilization. This is the case with the widespread disease beriberi, first described more than 1,300 years ago from that ancient seat of civilization, China. In modern times, however, it was not until towards the end of the 17th and the beginning of the 18th century that the disease attracted more general attention. Subsequently it has, on different occasions and with varying degrees of violence, made its appearance in all five continents, but more particularly its haunts have been in Eastern and South-Eastern Asia. At times the disease has been a serious scourge there. Thus in 1871 and 1879, Tokio was visited by widespread epidemics, and during the Russo-Japanese War it is said that not less than one-sixth of the Japanese army was struck down.

Beriberi shows itself in paralysis accompanied by disturbances in the sensibility and atrophy of the muscles, besides symptoms from the heart and blood vessels, inter alia, tiredness and oedema. Decided lesions have been shown in the peripheral nerves which seem to explain the manifestations of the disease. Mortality has varied considerably, from one or two per cent to 80 per cent in certain epidemics.

A number of circumstances indicated a connection between food and beriberi: for example, it was suggested that the cause might be traced to bad rice or insufficiency in the food of proteins or fat.

The severe ravages of beriberi in the Dutch Indies led the Dutch Government to appoint a special commission to study the disease on the spot. At the time, bacteriology was in its hey-day, and it was then but natural that bacteria should be sought as the cause of the disease, and indeed it was thought that success had been attained. The researches were continued in Java by one of the commission's coadjutors, the Dutch doctor Christiaan Eijkman. As has so often been the case during the development of science, a chance observation proved to be of decisive importance. Eijkman observed a peculiar sickness among the hens belonging to the laboratory. They were attacked by an upward-moving paralysis, they began to walk unsteadily, found difficulty in perching, and later lay down on their sides. The issue of the disease was fatal unless they were specially treated. It has been said that the secret of success is to be prepared for one's opportunity when it presents itself, and indubitably Eijkman was prepared in an eminent degree. With his attention focussed on beriberi, he immediately found a striking similarity between that disease and the sickness that had attacked the hens. He also observed changes in numerous nerves similar to those met with in the case of beriberi. In common with beriberi, this ailment of the hens was to be described as a polyneuritis. In vain, however, did Eijkman try to establish micro-organisms as the cause of the disease.

On the other hand, he succeeded in establishing the fact that the condition of the hens was connected with a change in their food, in that for some time before they were attacked they had been given boiled polished rice instead of the usual raw husked rice. Direct experiments proved incontestably that the polyneuritis of the hens was caused by the consumption of rice that by so-called «polishing» had been deprived of the outer husk. Eijkman found that the same disease presented itself when the hens were fed exclusively on a number of other starch-rich products, such as sago and tapioca. He also proved that the disease could be checked by the addition to the food of rice bran, that is to say, the parts of the rice that had been removed by polishing, and he found that the protective constituent of the bran was soluble in water and alcohol.

Eijkman's work led Vorderman to carry out investigations on prisoners in the Dutch Indies (where the prisoner's food was prepared in different ways according to the varying customs of the inhabitants), with a view to discovering whether beriberi in man was connected with the nature of the rice food they consumed. It proved that in the prisons where the inmates were fed on polished rice, beriberi was about 300 times as prevalent as in the prisons where unpolished rice was used.

When making investigations to explain the results reached, Eijkman considered that protein or salt hunger could not be the cause of the disease. But he indicated that the protective property of the rice bran might possibly be connected with the introduction of some particular protein or some special salt. At the time it might have been readily imagined that the polyneuritis in the hens and beriberi were due to some poison, and Eijkman set this up as a working hypothesis, though his attempts to establish the poison were in vain. In his view, however, such a poison was formed, but it was rendered innocuous by the protective substance in the bran. It was only Eijkman's successor in Java, Grijns, who made it clear that the substance in question was used directly in the body, and that our usual food, in addition to the previously known constituents, must contain certain other substances, if health is to be preserved. Funk introduced the designation vitamins for these substances, and since then the particular substance that serves as a protection against polyneuritis has been called the «antineuritic» vitamin.

It might have been expected that Eijkman's discovery would lead to an immediate and decided decline in beriberi - perhaps to the disappearance of the disease. But this was by no means the case, and not even in the Dutch Indies, where Eijkman and Grijns had worked, were the results particularly brilliant. The reasons for this were several: the reluctance of the inhabitants to substitute the less appetizing unpolished for polished rice, the opinion that polyneuritis in birds was not a similar condition to beriberi in man, and an inadequate appreciation of Eijkman's work. As a result of numerous experiments by different investigators on animals and human beings, who offered themselves for experimental work, it has gradually become clear that beriberi is a disease for the appearance of which lack of the vitamin found in rice bran - but also other circumstances - is of decisive importance. These experiences, in addition to successful experiments made in various places on the basis of Eijkman's observations, especially in British India, have gradually led to a general adoption of Eijkman's views. The successful attempts to combat beriberi which are now proceeding are the fruits of Eijkman's labours.

It was the analysis of the nature of the food used in cases of polyneuritis in hens that led Eijkman to his discovery. As a rule, analysis and synthesis complete each other, and indeed the employment of both these avenues of approach has been of decisive importance also for the development of the science of vitamins.

Bacteriophage Lambda

 
Bacteriophage λ is one of the most important model organisms but it's often omitted from the list, especially if the list has been written by anyone under 40.

Hop on over to The Evolutionary Biologist and read up on What has phage lambda ever done for us?. I mentioned in the comments that it's possible to create an entire course on the principles of molecular biology based on bacteriophage λ. That may be a bit of an exaggeration ... but not by much.

I believe strongly that you can't teach a course on developmental biology, for example, without describing the genetic switch in λ.

Today's students know nothing about the valuable contributions made by the phage group. That's a shame because it illustrates science in one of its purist moments. You shouldn't be allowed to graduate if you don't know the real reason why Max Delbrück and Salvador Luria got Nobel Prizes.

My Six Months Are Up!

 
I started Sandwalk six months ago. The goal was to give it six months to see how things worked out. I was told that you have to reach 1000 visits a day to be "successful" as a blogger and, as you can see, I didn't make it. But it's close—the average number of visits per day is a bit over 900.

It will take me a few days to evaluate the experiment.

The worst thing about Washington is ....

 
There's no Tim Horton's.

Everybody drinks Starbucks coffee. I don't like Starbucks and even if I did I have no idea how to order one. They seem to speak a different language. Whatever happened to "small," "medium,"and "large?"

Incidentally, the price of coffee is like the price of hotel rooms. It's outrageous but that doesn't seem to stop anyone from buying.

Everybody Should Have One of These

 
One of the most popular exhibits was the Leica booth. They set up a number of their most popular microscopes including the one shown in the photo. People gathered around drooling.

I wondered whether I could buy one so I asked the price, "three-fifty" was the answer. That's not bad. For only $350 dollars (US funds?) I'm thinking of getting one to put in my basement. Since I'm driving I don't have to worry about carrying it on a plane.

Herbert Tabor/Journal of Biological Chemistry Lectureship

 
One of the big events for ASBMB is the Herbert Tabor JBC lecture. It was held Saturday night in one of the large ballrooms. There were about one thousand people attending.

The first lecture was by Tony Hunter from The Salk Institute in California (USA). He spoke about mammalian kinases and phosphorylases with an emphasis on tyrosine kinases, which he discovered back in 1979. Tyrosine kinases are enzymes that attach phosphate groups to tyrosine residues in proteins. They are important because the phosphorylation and dephosphorylation of enzymes regulates their activity. Many of the genes that cause cancer (oncogenes) encode tyrosine kinases.

Hunter is trying to find out how many different proteins kinases there are in humans. The latest count suggests about 900 different enzymes. This is a remarkable number when you think about it. It means that 3-4% of all genes in our genome are kinases.

The second award winner was Tony Pawson from the Samuel Lunenfeld Research Institute and the University of Toronto (Ontario, Canada). I've heard Tony speak many times so I wasn't quite as attentive during his lecture. Tony discovered a number of proteins domains, notably the SH2 domain, that interact with tyrosine kinases and their target proteins. The work of the two Tony's is complementary and that's why they received this joint award.

UPDATE: I forgot to mention that there was a reception after the talks. Lots of delicious munchies and an open bar. I had a beer (or two). Most biochemists drink wine or fruit juice. It was not a wild bunch.

Monday's Molecule #24

 
Name this molecule. We need the exact name, preferably the correct one.

As usual, there's a connection between Monday's molecule and this Wednesday's Nobel Laureate. This one is dead easy. The prize (free lunch) goes to the person who correctly identifies both the molecule and the Nobel Laureate. (Previous free lunch winners are ineligible for one month from the time they first won.)

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