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Tuesday, November 11, 2008
November 11, 2008
This is what the front campus of the University of Toronto looks like today, Remembrance Day 2008. This is the 90th anniversary of the end of World War I.
Each cross bears the name of one of 628 alumni, students, or faculty members who died in World War I. It reminds us of what happens when we fail to resolve our differences peacefully. War is the failure of peace.
The crosses remind us that war is evil and horrible. All of these lives were wasted in a war that never should have happened. War is not glorious. War is not something we should be proud of even though we may honor those individuals who answered the call, and sacrificed their lives, when the politicians and diplomats failed to do their duty.
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Enzyme Efficiency: The Best Enzyme
One of the first things you learn about enzymes is that they catalyze, or speed up, reactions that would normally take place at a much slower rate. This is a difficult concept for students to understand because they're used to thinking of biochemical reactions in terms of reactions that would never happen without an enzyme.
The trick in understanding the role of enzymes is to appreciate the difference in rates between the enzyme-catalyzed reaction and the spontaneous reaction. While it's true that all enzyme-catalyzed reactions would eventually proceed even in the absence of enzyme, the rate of the spontaneous reaction might be way too slow. We often emphasize that the spontaneity of a reaction can be determined from the thermodynamics (i.e. if ΔG <0 the reaction is spontaneous) but we sometimes forget to show real data on how fast such a reaction can occur under physiological conditions. Typical rates for enzyme-catalyzed reactions are described by a constant called kcat.1 These values are usually in the range of 100-1000 reactions per second but there are some enzymes than have rates of over 1,000,000 reactions per second.
Spontaneous reactions can often approach these rates but, as you might imagine, the ones that require enzymes are very much slower. Proteins, for example, will eventually break down into amino acids but the rate of the reaction is so slow that spontaneous protein degradation is not a problem in living cells. In order to degrade proteins for food, we need to make enzymes such as chymotrypsin, trypsin, pepsin, and elastin to do the job at a faster rate.
Most of the important metabolic reactions take years in the absence of enzyme. The spontaneous degradation of a protein, for example, takes about 100 years (rate constant ~ 4 × 10-9). Since chymotrypsin catalzyes this reaction at a rate of about 1000 molecules per second, this means that the enzyme speeds up the reaction by a factor of more than 1011 (100 billion times)!
This value (1011) is sometimes called the catalytic proficiency of an enzyme although for technical reasons we won't go into here, the real measure of catalytic proficiency is higher by several orders of magnitude.1 The catalytic proficiency of chymotrypsin is 2 × 1016.
Naturally, this invites a comparison with those enzymes showing the greatest rate enhancements. But there's a problem. You can measure spontaneous rates that are on the order of a few years because you don't have to wait until the reaction goes to completion. But if the spontaneous reaction takes hundreds of years it can be difficult to measure—even the most dedicated graduate student won't wait that long!
Fortunately there are a few tricks that will make the job easier. You can observe the spontaneous reaction at high temperatures, for example, and calculate what the rate would be at physiological temperatures. That's what Radzicka and Wolfenden did in 1995 when they reported that the spontaneous decarboxylation of ornithine 5′-phosphate (OMP) had a rate constant of 3 × 10-16 s-1. This is a half-life of 78 million years.
The enzyme that catalyzes this reaction is ornithine 5′-phosphate decaboxlyase and up until last week it was the record holder with a catalytic proficiency of 2 × 1023. (OMP decarboxylase catalyzes an essential step in the synthesis of pyrimidine nucleotides that are required to make RNA and DNA.)
That record has now been broken. Lewis and Wolfenden (2008) studied a reaction catalyzed by uroporphyrinogen decarboxylase, an enzyme involved in the synthesis of porphyrins such as heme, the cofactor in hemoglobin, and the chlorophylls. There were able to model the reaction and determine that the rate of spontaneous decarboxylation is 9.5 × 10-18 s-1, which corresponds to a half-life of 2.3 billion years! Lewis and Wolfenden published a chart showing typical half-lives of spontaneous reactions.
The catalytic proficiency of uroporphyrinogen decarboxylase is 2.5 × 1024, a new record.
Into the textbook it goes.
The trick in understanding the role of enzymes is to appreciate the difference in rates between the enzyme-catalyzed reaction and the spontaneous reaction. While it's true that all enzyme-catalyzed reactions would eventually proceed even in the absence of enzyme, the rate of the spontaneous reaction might be way too slow. We often emphasize that the spontaneity of a reaction can be determined from the thermodynamics (i.e. if ΔG <0 the reaction is spontaneous) but we sometimes forget to show real data on how fast such a reaction can occur under physiological conditions. Typical rates for enzyme-catalyzed reactions are described by a constant called kcat.1 These values are usually in the range of 100-1000 reactions per second but there are some enzymes than have rates of over 1,000,000 reactions per second.
Spontaneous reactions can often approach these rates but, as you might imagine, the ones that require enzymes are very much slower. Proteins, for example, will eventually break down into amino acids but the rate of the reaction is so slow that spontaneous protein degradation is not a problem in living cells. In order to degrade proteins for food, we need to make enzymes such as chymotrypsin, trypsin, pepsin, and elastin to do the job at a faster rate.
Most of the important metabolic reactions take years in the absence of enzyme. The spontaneous degradation of a protein, for example, takes about 100 years (rate constant ~ 4 × 10-9). Since chymotrypsin catalzyes this reaction at a rate of about 1000 molecules per second, this means that the enzyme speeds up the reaction by a factor of more than 1011 (100 billion times)!
This value (1011) is sometimes called the catalytic proficiency of an enzyme although for technical reasons we won't go into here, the real measure of catalytic proficiency is higher by several orders of magnitude.1 The catalytic proficiency of chymotrypsin is 2 × 1016.
Naturally, this invites a comparison with those enzymes showing the greatest rate enhancements. But there's a problem. You can measure spontaneous rates that are on the order of a few years because you don't have to wait until the reaction goes to completion. But if the spontaneous reaction takes hundreds of years it can be difficult to measure—even the most dedicated graduate student won't wait that long!
Fortunately there are a few tricks that will make the job easier. You can observe the spontaneous reaction at high temperatures, for example, and calculate what the rate would be at physiological temperatures. That's what Radzicka and Wolfenden did in 1995 when they reported that the spontaneous decarboxylation of ornithine 5′-phosphate (OMP) had a rate constant of 3 × 10-16 s-1. This is a half-life of 78 million years.
The enzyme that catalyzes this reaction is ornithine 5′-phosphate decaboxlyase and up until last week it was the record holder with a catalytic proficiency of 2 × 1023. (OMP decarboxylase catalyzes an essential step in the synthesis of pyrimidine nucleotides that are required to make RNA and DNA.)
That record has now been broken. Lewis and Wolfenden (2008) studied a reaction catalyzed by uroporphyrinogen decarboxylase, an enzyme involved in the synthesis of porphyrins such as heme, the cofactor in hemoglobin, and the chlorophylls. There were able to model the reaction and determine that the rate of spontaneous decarboxylation is 9.5 × 10-18 s-1, which corresponds to a half-life of 2.3 billion years! Lewis and Wolfenden published a chart showing typical half-lives of spontaneous reactions.
The catalytic proficiency of uroporphyrinogen decarboxylase is 2.5 × 1024, a new record.
Into the textbook it goes.
1. A better description of an enzyme's real rate constant is kcat/Km.
Radzicka, A. and Wolfenden, R. (1995) A proficient enzyme. Science 267:90-93.
Lewis,C.A. Jr. and Wolfenden, R. (2008) Uroporphyrinogen decarboxylation as a benchmark for the catalytic proficiency of enzymes. Proc. Natl. Acad. Sci. (USA) published online November 6, 2008 [Abstract] [doi:10.1073/pnas.0809838105]
Monday, November 10, 2008
Saturday Night Live: Joan Baez
On Saturday night we went to see Joan Baez. She older than she used to be but still wonderful. I remember her from the 60s in spite of what they say.1
If you remember the 60s, you weren't there.
Molecular and Cell Biology Carnival #4
The 4th issue of the Molecular and Cell Biology Carnival has been posted by steppen wolf at the skeptical alchemist [Molecular and Cell Biology Carnival #4].
Welcome to the fourth edition of the Molecular and Cell Biology Carnival! Let's get down to business right away...Submit your articles here.
The previous editions are ...
Monday's Molecule #96
You haven't been very successful lately at guessing Monday's "Molecule" so this week is going to be an easy one. All you have to do is identify the molecules (plural) that are responsible for this strange looking fly. Just naming the genes will be sufficient.
This week's Nobel Laureate won the prize for his work on these genes (and several others).
The first one to correctly identify the molecules/genes and name the Nobel Laureate(s), wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first collected the prize. There are only two ineligible candidates for this week's reward: Bill Chaney of the University of Nebraska and Dima Klenchin of the University of Wisconsin. Since they are two of the three most frequent winners, the competition is a bit easier this week.
THEME:
Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Laureate(s) so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.
Correct responses will be posted tomorrow. I reserve the right to select multiple winners if several people get it right.
UPDATE: The mutant Drosohila melanogaster is called "bithorax" because it has two pairs of wings instead of just one pair. It actually doesn't have two thoraces, instead the 3rd thoracic segment is transformed into a duplicate of the second thoracic segment. The complete transformation requires two different mutations called bx, and pbx. Both mutations are in the regulatory region of the gene UBX and they affect expression of that gene. The Nobel Laureate is Edward Lewis.
The winner is Dale Hoyt from Athens, Georgia (USA).
Friday, November 07, 2008
How 'molecular machines' kick start gene activation revealed
That's the title of a press release published on Biology News Net, and several other science news sites. Here's the opening sentence ...
How 'molecular machines' inside cells swing into action to activate genes at different times in a cell's life is revealed today (6 November) in new research published in Molecular Cell.How could you not want to find out more? This sounds like a real breakthrough.
Try and guess what the new discovery is all about before reading on ...
From the website Biology News Net and Imperial College London ...
Genes are made of double stranded DNA molecules containing the coded information an organism's cells need to produce proteins. The DNA double strands need to be 'melted out' and separated in order for the code to be accessed. Once accessed, the genetic codes are converted to messenger RNAs (mRNA) which are used to make proteins. Cells need to produce particular proteins at different times in their lives, to help them respond and adapt to changes in their environment.I'm underwhelmed. How is science journalism ever going to be taken seriously if this is the sort of thing that university press offices publish?
The new study outlines exactly how a molecular machine called RNA polymerase, which reads the DNA code and synthesizes mRNA, is kickstarted by specialised activator proteins. The scientists have discovered that RNA polymerase uses a tightly regulated internal blocking system that prevents genes from being activated when they are not needed.
We've known and understood the basics of transcription initiation by RNA polymerase and its activators for thirty years. This study concerns a minor variation of that process involving σ54 in bacteria.
Never Let Your Gas Tank Get Below Half Full
Friday's Urban Legend: True
How many of you have heard the story that you should always drive your car with the gas tank as full as possible? According to many, you should never let the gas in your tank fall below the half full mark on your gas gauge.
You probably thought this was a tale told by elderly wives—with apologies to old men who also tell tales.
Well, it turns out that there is actual, scientific, evidence to support this warning. Cliff Allen did the experiment according to the Sept. 13, 2008 issue of New Scientist [Petrol Gauge Challenge].
SLIGHTLY more practical routes to fuel economy occurred to Cliff Allen when he noticed that, according to his petrol gauge, the fuel in the top half of his tank lasted considerably longer than the bottom half. As any Feedback reader (and possibly only a Feedback reader) would, he investigated. Systematically.
Over several months he recorded the distances travelled using the fuel from the top and bottom halves. The average for the top was 400 kilometres (250 miles) and for the bottom a mere 300 kilometres (185 miles). Since then, he writes, "of course I have only used the top of my tank and have consistently achieved around 250 miles - I'm not stupid!"
Cliff was obviously keen to discuss this, at length, with his learned friends, "some of whom gained General Certificate of Secondary Education qualifications" at age 14. He was "mostly appalled at their incredulity and lack of interest".
However, his friend Alan suggested that the fact that petrol always comes out of the bottom of the tank causes it to use more petrol so we might benefit from turning the tank upside-down. John suggested the increased efficiency might be due to the height of the fuel, so the tank should be put on the roof. Mostyn proposed putting a brick in the tank, as this apparently works very well for saving water in toilet cisterns. Tony wants to make the top of the tank larger than the bottom, to increase the proportion of its volume at the top, and thinks a carrot shape would be optimal.
P.S. for the irony impaired.
Labels:
Humor
,
Urban Legend
Thursday, November 06, 2008
The Awesome Power of Prayer
James C. Dobson, Ph.D. is Founder and Chairman of Focus on the Family. He is not a fan of Barrack Obama and came to the realization that John McCain and Sarah Palin would be much better for the country.
Dobson urged his followers to pray [Dr. Dobson’s October Newsletter].
Regardless of your political views, I want to urge Christians everywhere to be in prayer about this election. There are many scriptural references wherein King David “inquired of God” when he was faced by troubling circumstances (1 Samuel 23:2,4; 30:8; 2 Samuel 2:1; 5:19,23). It is time for Christians everywhere to turn to Him for guidance and wisdom. Find some time to be still and listen to what He wants to tell you. The National Day of Prayer Task Force, led by my wonderful wife, Shirley, has embarked on a national campaign entitled “Pray for Election Day.” All around the country, individuals and groups are being encouraged to gather every Thursday leading up to Nov. 4 between 12 noon and 12:30 p.m. Spend time with the Lord, asking Him to guide and direct those privileged to cast a ballot. If you are able, I would also encourage you to fast and pray immed”ately before the election. After all, it was the Reverend Billy Graham who once said that “To get nations back on their feet, we must first get down on our knees.”20 Amen, Dr. Graham.Apparently God was listening. He answered their prayers on Tuesday. Here's how Tom Hess describes the result [‘We Need to Continue to be in Prayer for America’].
This election is about the future of the nation, but it will also go a long way toward determining the culture your children and grandchildren will come to know. I know you will vote with your children and your children’s children in mind. That certainly puts the election in a different light, doesn’t it?
With an Obama administration forthcoming, Focus Action’s Tom Minnery says, “We’ve got a big challenge ahead of us.”You can't make this stuff up.
He and FRC Action President Tony Perkins encouraged CitizenLink viewers to remain hopeful of what God might do in the next four years — and to be in prayer.
“For those who have been praying for weeks, our responsibility does not end today,” Perkins said. “In Luke 18, Jesus said men should not lose heart, but they should pray. We need to continue to be in prayer for America.”
Minnery pointed out that in the Bible, God worked through pagan rulers such as Nebuchadnezzar, Darius and Cyrus to accomplish his purposes, and that values voters ought to begin praying for President-elect Obama.
“God can use any president for his own purposes,” Minnery said.
[Hat Tip: Primordial Blog]
It's Her Last Saturday in the Lab
Eva Amsen blogs at Expression Patterns on the Nature Network [Last Saturday]. My department will miss her when she leaves.
Small Science Is Good Science?
I've been thinking a lot lately about what's wrong with science in the 21st century. Part of the problem is sloppy thinking that becomes apparent when you realize how many widely believed models are inconsistent with what we know about biology. I assume that similar problems occur in other disciplines.
One wonders if the proliferation of papers with huge numbers of authors is part of the problem. Maybe this fad of "multidisciplinary" science is part of the problem and not part of the solution? Is it possible to be an expert in two or more different disciplines?
I've seen plenty of example of biochemists and molecular biologists who publish papers about evolution without knowing much about evolution. Is this an isolated example?
Speaking of "big science," I was reminded of a paper published by Bruce Alberts back in 1985 in Cell. The title was "Limits to growth: In biology, small science is good science" (Alberts 1985).
These days, many people grow up believing that bigger is better. Giant factories that produce Wonder Bread have replaced thousands of corner bakeries, driven by the increased efficiency of scale. There is an unfortunate tendency to extend this view to the biological research community, and I have on occasion heard a major symposium speaker introduced in glowing terms as the coauthor of more than fifty papers per year. While I can admire the energy and management skills required to maintain a very large laboratory, the best biology is rarely done in this way. With a few notable exceptions, the biochemists and molecular biologists I most respect run relatively small laboratories and publish when they have something important to report. As I shall argue here, doing good science is very different from producing bread, and there are compelling reasons why large laboratories are in general less efficient and less interesting than smaller ones. To reflect this fact, I believe that changes in funding patterns and expectations would be useful in the biological sciences.Some "big science" is good. The sequencing of the human genome, and other genomes, for example, was a big science project that benefited the entire biological community. But I'm not sure that significant advances in our understanding of how life works come from big labs. Does anyone have examples? What are the most significant conceptual advances to come out of big labs?
Alberts, B.M. (1985) Limits to growth: In biology, small science is good science. Cell 41:337-338. [PubMed] [doi:10.1016/S0092-8674(85)80001-5]
Ignore, Reject, Answer? What to Do about Student Email Messages
Some of my colleagues are running courses where they ask students to write essays on science subjects. Part of the assignment is to contact a Professor in the discipline and get them to help with the scientific content of the essay. The idea is for the students to make sure they have their facts correct. A side benefit is that it gets the students in touch with active researchers.
Some of us object to this procedure on the grounds that if it became widespread there would be hundreds of students looking for Professors to help them on their assignment. Most Professors have other priorities, like teaching their own classes. To some extent, our colleagues who engage in this practice are downloading their teaching responsibilities onto others.
From 1992-2000 I ran a molecular biology course where the students had to write a major essay. They were told to do the research themselves but the instructors would be available if they need help with the interpretation of some papers. If necessary, we would put them in touch with an expert but only after the student had done enough work to ask intelligent questions on difficult material.
Here's an email message that was sent to my Sandwalk address last night. How should I respond? I don't feel comfortable ignoring the message. I will feel awkward if I refuse to help. I don't had time to answer the question—it's complicated and, besides, it's not my area of expertise.
Dear Professor Moran,This makes me angry. No matter what I do, I'm going to be disappointing a student who might really benefit from a reply. In my opinion the student's Professor is at fault for assigning such a task to the students.
As part of a University assignment, I have been asked to email a group of experts to request their professional opinion on a particular question.
I have come to understand that a child with Dyspraxia should supplement their diet with a high dose of essential fatty acids. However, as non-Dyspraxic people age it is advised that they also should supplement their diet with these oils to combat age-related memory loss. Does this mean that people with Dyspraxia should augment their intake yet again when they age? If so, could this have an adverse effect on their health?
As your organisation came up in an internet search as being reputable, your answer to this question would be much appreciated.
I would like to thank you for taking the time to read this email and I hope to hear from you soon.
Yours sincerely,
Wednesday, November 05, 2008
Barack Obama Will Save Religion in America
Frank Scaheffer writes in The Huffington Post [President Obama: Bad News For the New Atheists and Other Fundamentalists].
The Obama presidency is great news for almost everyone. It's bad news for some odd ideological bedfellows: the Religious Right and the so-called New Atheists.Who knew? I bet all atheists and agnostics are feeling pretty stupid right now knowing that they've been tricked by the slick-talking Obama.
Into the all or nothing culture wars, and the all or nothing wars between the so-called New Atheists and religion the election of President elect Obama reintroduces nuance. President elect Obama's ability to believe in Jesus, yet question, is going to rescue American religion in general and Christianity in particular, from the extremes.
There is no way to understand President elect Obama's victory as anything less than the start of not just a monumental political change but a spiritual revolution as well.
And what is the "nuanced" spiritual revolution going to look like?
To the New Atheists who think that with the resounding defeat of the Religious Right, we are entering a secular age, think again. Obama will block your path. He'll do it for the same reason he'll make the Religious Right's paranoid fantasies about him soon seem shamefully ridiculous. That's because President elect Obama is that rarest of all rare people: a thoughtful, compassionate and likable statesman who also is a thoughtful, compassionate and likable religious believer.Sounds like trouble. President Obama is going to block the path to a secular society. Gosh. I knew that American Presidents were leaders of the free world and the most powerful men (no women so far) on the planet but even I had no idea they were that powerful.
President-elect Obama brings another perspective to faith . It goes something like this:Ohmygod. Frank Shaeffer and Barack Obama have discovered the atheist dirty little secret. All of us atheists are flat and dull—we can't be born, get married, or die without calling upon God to help us.
How do cultures define themselves if not through ritual? In the "big moments" of life; birth, marriage, sickness, death "who" -- in the inimitable words of Ghost Busters -- "you gonna call?" As President elect Obama has said, and I paraphrase: Strip the human race of our spiritual language and what do we tell each other about hope?
As President elect Obama has pointed out, a world of all math but no poetry is not fit for human habitation. If everything feels flat and dull, stripped of mystery and meaning who will bother to do the science? Why bother, if all we're doing is serving those selfish genes for another round of meaningless propagation?
So does this faith always make "sense?" No. Because our perspective is from the inside, something like paint contemplating the painting of which it's a part. We're all in the same boat, all stuck on the same "canvas."
Does anyone actually believe this stuff?
[Hat Tip: RichardDawkins.net]
Evolution by Gene Duplication
Chymotrypsin (Monday's Molecule #95), trypsin, and elastase are enzymes that digest proteins in the stomach and intestine. All three enzymes have a similar mechanism of hydrolysis characterized by the presence of a catalytic triad of amino acid side chains consisting of aspartate, histidine, and serine residues. The serine side chain is directly involved in catalyzing the cleavage of proteins and that's why these enzymes are called serine proteases.
The three enzymes differ in specificity. Chymotrypsin cleaves foreign proteins primarily at tyrosine (Tyr) resides, trypsin is specific for cleavage at arginine (Arg) or lysine (Lys) resideus, and elastin cleaves at alanine (Ala) residues.
The genes for the three enzymes are homologous and the structures of the three enzymes are very similar as shown below (left: chymotrypsin [PDB 5CHA], middle: trypsin [PDB 1TLD], right: elastase [PDB 3EST]).
The active sites of the enzymes are slightly different so that specificity depends on which amino acid side chains of the substrate protein fit into the binding pocket.
It's reasonable to suppose that the primitive enzyme could bind weakly to many different substrates and cleave many different kinds of proteins inefficiently. An ancient gene duplication allowed one copy of the gene to evolve toward a much more active enzyme that cleaved only at certain residues. A second gene duplication gave rise to a third enzyme that cleaved at another residue. Finally the remaining gene evolved into a very active enzyme that cut at a third position.
The end result was a set of three enzymes that could cut up any protein into small peptides that can be taken up by the cells lining the intestine. The original non-specific enzyme was slower and less efficient.
This is an example of evolution by gene duplication and the important point is that the ancestral gene probably encoded a non-specific enzyme that could carry out several different reactions with different substrates. It's not a question of the duplicated copy evolving an entirely new specificity. Instead, the duplicated gene usually "perfects" an already existing minor activity by becoming more specific. Meanwhile, the other copy can also be selected for enhanced specificity for another substrate.
This model also explains the evolution of lactate dehydrogenase and malate dehydrogenase (Evolution and Variation in Folded Proteins) and the pyruvate dehydrogenase family (Pyruvate Dehydrogenase Evolution).
The three enzymes differ in specificity. Chymotrypsin cleaves foreign proteins primarily at tyrosine (Tyr) resides, trypsin is specific for cleavage at arginine (Arg) or lysine (Lys) resideus, and elastin cleaves at alanine (Ala) residues.
The genes for the three enzymes are homologous and the structures of the three enzymes are very similar as shown below (left: chymotrypsin [PDB 5CHA], middle: trypsin [PDB 1TLD], right: elastase [PDB 3EST]).
The active sites of the enzymes are slightly different so that specificity depends on which amino acid side chains of the substrate protein fit into the binding pocket.
It's reasonable to suppose that the primitive enzyme could bind weakly to many different substrates and cleave many different kinds of proteins inefficiently. An ancient gene duplication allowed one copy of the gene to evolve toward a much more active enzyme that cleaved only at certain residues. A second gene duplication gave rise to a third enzyme that cleaved at another residue. Finally the remaining gene evolved into a very active enzyme that cut at a third position.
The end result was a set of three enzymes that could cut up any protein into small peptides that can be taken up by the cells lining the intestine. The original non-specific enzyme was slower and less efficient.
This is an example of evolution by gene duplication and the important point is that the ancestral gene probably encoded a non-specific enzyme that could carry out several different reactions with different substrates. It's not a question of the duplicated copy evolving an entirely new specificity. Instead, the duplicated gene usually "perfects" an already existing minor activity by becoming more specific. Meanwhile, the other copy can also be selected for enhanced specificity for another substrate.
This model also explains the evolution of lactate dehydrogenase and malate dehydrogenase (Evolution and Variation in Folded Proteins) and the pyruvate dehydrogenase family (Pyruvate Dehydrogenase Evolution).
Nobel Laureate: John Howard Northrop
The Nobel Prize in Chemistry 1946.
"for their preparation of enzymes and virus proteins in a pure form"
John Howard Northrop (1891 - 1987) was a renowned protein chemist who developed techniques for purifying and crystallizing enzymes.
He shared the prize with James Sumner, who first showed that proteins could be crystallized and with Wendell Stanley who crystallized tobacco mosaic virus.
Most biographers note that Northrop was very interested in genealogy and was proud to point out that he was a direct descendant of Joseph Northrop who settled in New Milford Connecticut in 1636 (John H. Northrop). I don't know if any other Nobel Laureates can trace their North American ancestors back 400 years.
The significanc of Northrops work is summarized in this excerpt from the presentation speech on the Nobel Prize website.
THEME:
Nobel Laureates
Doctor John Northrop. You and your collaborators have developed the crystallization of enzymes and other active proteins into an art, of which you are the masters. The conditions for successful work in this field were explored by you, and in the course of that work interesting relationships between enzymes and related proteins were discovered, which may ultimately afford a clue to a fuller understanding of the mode of action of these substances.We now know that trypsin, pepsin, and chymotrypsin are similar proteases that cleave other proteins. We also know that the active enzymes are derived from inactive precursors called zymogens. The zymogens (pepsinogen, trypsinogen, and chymtrypsinogen) are cleaved to remove part of the protein making the remainder into an acive enzyme. It's interesting to see how John H. Northrop described this discovery in his acceptance speech.
Formation of enzymes from their precursors. Pepsin, trypsin, and chymotrypsin are derived from inactive precursors. These precursors were isolated and crystallized and the formation of the active enzyme studied. The formation of pepsin from pepsinogen and trypsin from trypsinogen are autocatalytic reactions. These enzymes may therefore be "propagated", just as are bacteria. The formation of trypsin from trypsinogen may also be catalyzed by enterokinase, an enzyme of the digestive tract, or by an enzyme produced by a mold (Penicillium.) The formation of chymotrypsin from chymotrypsinogen is catalyzed only by trypsin, so far as is known. In all these reactions the increase in enzymatic activity is accompanied quantitatively by the appearance of the new enzyme protein which is quite different in all its properties from the original precursor. It seems to me that these results are perhaps the most convincing evidence that the enzymatic activity is actually a property of the protein molecule.
What Does Change Look Like?
I'm glad Barrack Obama won the election. He is much less conservative than John McCain and much more likely to do good things for America.
Change is in the air, everybody is talking about a new direction for America under Barack Obama. What kind of changes can we expect? Here's a sample from last night's vote on several propositions [CNN.com].
This measure would amend the state constitution so that only a union between one man and one woman would be valid or recognized as a marriage in the state. A similar measure was on the ballot in 2006 but failed.According to the exit poll [Arizona Prop.102], 67% of Protestants voted to ban gay marriage as did 51% of Catholics. About 13% of voters said they had no religion and 69% of them voted against Proposition 102.
This measure would prohibit unmarried "sexual partner[s]" from adopting children or from serving as foster parents. The measure specifies that the prohibition applies to both opposite-sex as well as same-sex couples.According to the exit poll [Arkansas Initiative 1], the voters are evenly split between Democrats, Republicans, and Independents. Democrats voted against the initiative (52%) but the other two groups voted in favor of the ban. A majority of college graduates (52%) and those with postgraduate education (54%) voted in favor of the ban on adoptions.
This measure would amend the state constitution to specify that only marriages between one man and one woman would be recognized as valid in the state. If passed, the measure would trump a May 2008 ruling by the California Supreme Court that legalized same-sex marriage.According to the exit poll [California Proposition 8], a majority of whites (53%) and Asians (53%) voted against Proposition 8 while a majority of African-Americans (70%) and Latinos (51%) voted in favor of the ban. Democrats (65%) and Independents (56%) were against the ban but 81% of Republicans voted in favor of the ban on gay marriage.
This measure would amend the state constitution to define the term "person" to include "any human being from the moment of fertilization." This definition would be applied to all aspects of the state constitution, including the provisions that ensure that no person has his or her life, liberty, or property taken away without due process of law. Thus, the measure would essentially have the effect of banning abortion.According to the exit poll [Colorado Amendment 48], this amendment should have been approved by a substantial majority.
This measure would amend the state constitution to define marriage as a union between one man and one woman. In order to amend the Florida constitution, 60 percent of voters must vote in favor of the amendment.According to the exit poll [Florida Amendment 2], 71% of Protestants and 66% of Catholics voted in favor of the amendment to ban gay marriage. A majority of Whites (60%), African-Americans (71%), and Latinos (64%) voted for the ban.
This measure would prohibit all abortions in the state except in cases where mother's life or health is at risk or in cases of rape or incest for pregnancies of less than 20 weeks. A similar measure that did not include exceptions for rape or the health of the mother was on the ballot in 2006, but was rejected by voters 44 to 56 percent.According to the exit poll [South Dakota Initiative 11], only evangelical born-again Christians and conservative Republicans supported the initiative. A majority of all other groups voted against it.
This measure would allow terminally ill, competent, adult residents of the state to request and self-administer lethal medication prescribed by a physician. The person requesting to end his or her life must be medically predicted to have six months or less to live.According to the exit poll [Washington Initiative 1000], this initiative was supported by liberals (81%) and moderates (63%) and opposed by conservatives (66%). There are more liberals (29% of the voters) than in most states. Republicans (63%) voted against the initiative while Democrats (75%) and Independents (59%) voted for it.
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