Time to Re-Write the Textbooks! Nature Publishes a New Version of the Citric Acid Cycle

I was looking through my copy of Nature the other day trying to take seriously all the special reviews on "Transcription and Epigenetics." One article caught my eye ...

Gut, P. and Verdin, E. (2013) The nexus of chromatin regulation and intermediary metabolism. Nature 502:489-498. [doi: 10.1038/nature12752]

Living organisms and individual cells continuously adapt to changes in their environment. Those changes are particularly sensitive to fluctuations in the availability of energy substrates. The cellular transcriptional machinery and its chromatin-associated proteins integrate environmental inputs to mediate homeostatic responses through gene regulation. Numerous connections between products of intermediary metabolism and chromatin proteins have recently been identified. Chromatin modifications that occur in response to metabolic signals are dynamic or stable and might even be inherited transgenerationally. These emerging concepts have biological relevance to tissue homeostasis, disease and ageing.

The authors argue that, among other things, methylation of histones is regulated by changes in the concentrations of some citric acid cycle metabolites. I find it difficult to imagine that the concentrations of the citric acid cycle intermediates could change significantly enough to act as allosteric effectors but that's not what grabbed my attention.

It's the figure showing the citric acid cycle (TCA cycle) that shocked me.

Textbooks show that the products of the citric acid cycle are ...

That's three NADH, one QH₂, and one GTP (or ATP) for a total of ten ATP equivalents. The new version, published last week in the most prestigious science journal in the world, shows that there are six NADH produced per cycle for a total of 15 ATP equivalents. It must be correct because this is a paper about intermediary metabolism and it was reviewed by experts in the field. Unfortunately, the authors don't give a reference to this new information. I assume that it's common knowledge among the top metabolism researchers so they didn't bother citing the papers.

Can anyone out there direct me to the revolutionary papers that I missed?

P.S. I'm not even going to mention that FADH₂ is NOT a product of enzyme-catalyzed β-oxidation.

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I Just Signed Up for an Evolution MOOC!

I'm not a big fan of MOOCs but I just couldn't resist a course called "Evolution: A Course for Educators". The instructors are two Ph.D. employees from the American Museum of Natural History in New York (USA). As you probably know, the American Museum of Natural History is very proud of its tradition in education. Here's what they say on their website.

The American Museum of Natural History is one of the world’s preeminent scientific, educational and cultural institutions. Since its founding in 1869, the Museum has advanced its global mission to discover, interpret, and disseminate information about human cultures, the natural world, and the universe through a wide-ranging program of scientific research, education, and exhibition.

This is a course for educators and that's right up my alley. You may want to sign up as well. Here's the description and the video.

How are all of the species living on Earth today related? How does understanding evolutionary science contribute to our well-being? In this course, participants will learn about evolutionary relationships, population genetics, and natural and artificial selection. Participants will explore evolutionary science and learn how to integrate it into their classrooms.

....

The AMNH course Evolution: A Course for Educators provides an overview of biological evolution for educators. Informed by the recently released Next Generation Science Standards, the course explores the history of evolutionary theory and the evidence that supports it. We will learn about patterns of human evolution and societal implications of modern evolutionary biology, and how scientists determine relatedness among living and extinct organisms. Course participants will bring their understanding of course themes - along with content resources, discussion questions, and assignments - into their own teaching.

It's a bit disturbing that the Next Generation Science Standards don't mention random genetic drift, Neutral Theory, speciation, or population genetics [Natural Selection and Evolution] but the course promises to cover population genetics and I assume that it will also cover all mechanisms of evolution since it's being taught by an evolutionary biologist (Joel Cracraft).

The purpose of the course is to train the next generation of high school (and university) teachers. One of the instructors, David Randle, is an expect on education. We all know that teachers need to be updated on modern evolutionary theory.

It starts next Monday. I'll let you know how I'm doing when I write the first test.

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The Khan Academy and AAMC Teach Evolution in Preparation for the MCAT

Ross Firestone is a 2nd year MD/PhD student at the Albert Einstein College of Medicine. He is one of the winners of the MCAT Video Competition. Apparently the Khan Academy and the Association of American Medical Colleges were impressed with his presentations on evolution. You can see all six videos at Evolution and population dynamics.

I'm posting the first one on Evolution and Natural Selection. It's all about natural selection but it's a very strange kind of natural selection. The organisms are parthenogenic and each individual is genetically programed to have a certain probability of reproducing. One type has a 50% probability of reproducing and another type has only a 25% probability of reproducing. These probabilities seem to be independent of any competition between them. Each successful individual produces four offspring. After some time the number of one type remains constant (25% probability) but the number of the other type (50% probability) doubles with each generation. This is natural selection according to Ross Firestone.

"Naturally," I was disappointed that natural selection was the only mechanism mentioned. There's nothing about random genetic drift in this video and nothing about the stochastic nature of natural selection. But my face lit up when I saw that there was another video on "Alternative Selection: Learn about driving forces of evolution other than natural selection." This could almost make up for screwing up the description of natural selection.

Alas, the second video is even worse. The "alternatives" are group selection and artificial selection. It gets even more worse. The example of group selection is the grandmother hypothesis. According to Ross Firestone, the fact that grandmothers help their grandchildren survive is group selection.

The video on "Bottlenecks and the environment" is also quite interesting. I didn't know that that the peppered moth story is an example of a bottleneck. Did you?


I think these videos are horrible—so horrible, in fact, that the Khan Academy should take them down. What do you think?

Are you wondering why a 2nd year med student feels so confident that he knows enough about evolution to teach it to pre-med students? Me too.

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The Khan Academy and AAMC Teach the Central Dogma of Molecular Biology in Preparation for the MCAT

Here's a presentation by Tracy Kovach, a 3rd year medical student at the University of Virginia School of Medicine. Sandwalk readers will be familiar with my view of Basic Concepts: The Central Dogma of Molecular Biology and the widespread misunderstanding of Crick's original idea. It won't be a surprise to learn that a 3rd year medical student is repeating the old DNA to RNA to protein mantra.

I suppose that's excusable, especially since that's what is likely to be tested on the MCAT. I wonder if students who take my course, or similar courses that correctly teach the Central Dogma, will be at a disadvantage on the MCAT?

The video is posted on the Khan Academy website at: Central dogma of molecular biology. What I found so astonishing about the video presentation is that Tracy Kovach spends so much time explaining how to remember "transcription" and "translation" and get them in the right order. Recall that this video is for students who are about to graduate from university and apply to medical school. I expect high school students to have mastered the terms "transcription" and "translation." I'm pretty sure that students in my undergraduate class would be insulted if I showed them this video. They would be able to describe the biochemistry of transcription and translation in considerable detail.


There are people who think that the Central Dogma is misunderstood to an even greater extent than I claim. They say that the Central Dogma is widely interpreted to mean that the only role of DNA information is to make RNA which makes protein. In other words, they fear that belief in that version of the Central Dogma rules out any other role for DNA. This is the view of John Mattick. He says that the Central Dogma has been overthrown by the discovery of genes that make functional RNA but not protein.

I wonder if students actually think that this is what the Central Dogma means? Watch the first few minutes of the video and give me your opinion. Is this what she is saying?

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The Khan Academy and the Association of American Medical Colleges (AAMC) Team Up to Teach Evolution and Biochemistry for the New MCAT

Theme

Better BiochemistryStudents have to write an exam called the MCAT in order to get into American Medical Schools (Canadians students also write the MCAT). The exam is created and marked by the Association of American Medical Colleges (AAMC). The format of the exam is changing in 2015 to include more biochemistry and molecular biology. This means that "pre-med" students will likely be taking more biochemistry and molecular biology courses.

Most American schools teach to the MCAT in their biochemistry and molecular biology courses because there are large numbers of wannna-be doctors in their class. The biochemistry lecturers feel that it's their duty to prep the pre-med students to pass the MCAT. This has a devastating effect on American biochemistry courses [Better Biochemistry: Teaching to the MCAT?] [Better Biochemistry: Teaching ATP Hydrolysis for the MCAT]. It is inconsistent with the American Society for Biochemistry and Molecular Biology (ASBM) goals of developing concept-driven courses that focus on fundamental principles [Fundamental Concepts in Biochemistry and Molecular Biology ].

The Khan Academy is taking advantage of the new MCAT in 2015 by posting a series of videos on basic biochemistry and evolution. The content is approved by the AAMC in order to make sure it is suitable for MCAT preparation. Here's what they say on their website [Khan Academy MCAT].

This collection is being developed for the revised MCAT® exam that will first be administered in spring 2015. Videos will be added to the collection through fall 2014. All content in this collection has been created under the direction of the Khan Academy and has been reviewed under the direction of the Association of American Medical Colleges (AAMC). All materials are categorized according to the pre-health competencies tested by the MCAT²⁰¹⁵ exam; however, the content in this collection is not intended to prescribe a program of study for the MCAT²⁰¹⁵ exam. The content is also included in the Pre-health Collection within MedEdPORTAL’s iCollaborative sponsored by the AAMC: www.mededportal.org/pre-health *MCAT® is a program of the AAMC and related trademarks owned by the Association include Medical College Admission Test, MCAT, and MCAT²⁰¹⁵. For more information about the MCAT exam visit : www.aamc.org/mcat2015.

So, how did the Khan Academy prepare the videos? They set up an MCAT Video Competition and picked the best ones. You can read about the winners at MCAT Video Competition Winners. It's an eclectic mix of people but 11 out of 15 winners are medical school students or graduate students. Keep in mind that teaching introductory subjects like evolution and biochemistry is hard and Teachers Have to Know Their Subject.

I'm going to look at the videos on evolution prepared by a second year MD/PhD student at Albert Einstein College of Medicine and videos on biochemistry prepared by a second year MD student at Harvard Medical School and a third year med student at the University of Virginia School of Medicine. Medical students are very bright and very confident of their abilities. We'll see if these students learned enough in their undergraduate courses to be able to create accurate videos that will help university graduates pass the MCAT.

Before looking at some specific examples, let me make a general comment on Khan Academy videos. I've looked at quite a few of them over the years and every single one I've seen is a "kindergarten-level" video. What I mean by that is that the level of the presentation is barely suitable for students beginning high school and in some cases they really are pitched at the level my three-year old granddaughter could understand in a year or two. They certainly aren't up to the level of any university course that I've ever taught.

These MCAT videos are no exception. But they are intended for students who are about to graduate from university. Most of these students will be getting a science degree. The mini courses are intended for students who are about to write the MCAT exam and this should represent the level of knowledge expected of medical students. As a general rule, the students who are preparing for the MCAT have achieved high grades in their biology and chemistry courses and in their biochemistry and molecular biology courses. They wouldn't be considering medical school if they weren't in the top 25% of their class.

Why are the videos pitched at such a low level of education? Is this truly representative of the quality of university education in American universities? Check them out for yourself at: Biomolecules.

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Teachers Have to Know Their Subject

I've said it before and I'll say it again. The top three criteria for good teaching are: (1) accuracy, (2) accuracy, and (3) accuracy. Everything else is in fourth place or lower and that includes style. If what you're teaching is not accurate then nothing else matters.

It is hard to teach an introductory science course. You have to go back to basics and make sure that what you cover all the fundamental principles and concepts and that ain't easy. That's why the best teachers in introductory courses are often senior professors and lecturers with plenty of experience behind them. They have learned what's important and what's not and they can tell the difference between wheat and chaff.

PZ Myers puts it very well in a blog post defending teachers [Teaching is so easy, anyone can do it!].

One of the first things you learn when you start teaching is that you have to know the content inside and out — it’s simply not enough to know the bare minimum that you expect the students to master, because as a teacher, you need to push just a bit farther to get them up there. You need to be able to lead them to knowledge, and you need to be able to point off in the distance to all the cool stuff they can learn if they continue. How can you inspire if you’re not drinking deeply from the Pierian Spring yourself?

Keep this in mind next time we discuss teaching evolution and biochemistry. Teachers have to be experts and it takes a lot of work to make sure you know your content. If what you're teaching is not correct then you are not a good teacher no matter what the student evaluations say. And it's not only a question of accuracy—as PZ points out, you need to be more than a few steps ahead of your students in order to inspire them to do better.

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Submitting to Carnival of Evolution

PZ Myers is hosting the next Carnival of Evolution [Guess who’s hosting the Carnival of Evolution?]. I tried submitting an article but I was unable to read the stupid fuzzy words that you need to type before submitting. Now I can't submit unless I log in. When I do that, my time seems to expire before I can enter the necessary information. Very frustrating.

So, I figured I would just add a comment on PZ's blog. Easier said than done. You have to log in to his blog and none of my usual names and passwords work. I'm beginning to understand why submissions to the Carnival of Evolution are way down.

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Michael Egnor Keeps Digging

When you find yourself in a hole, stop digging.
Will RogersI favor teaching biochemistry from an evolutionary perspective and I was pleased to see that ASBMB considers evolution to be one of the fundamental concepts in biochemistry and molecular biology [ASBMB Core Concepts in Biochemistry and Molecular Biology: Evolution]. (ASBMB screws up their description of evolution but at least their heart's in the right place.)

Unless they understand evolution, students can't really understand why some parts of a protein are the same in all species and other parts are quite variable. They certainly can't understand why you can construct a phylogenetic tree from sequences and why this tree closely resembles those trees made from comparing anatomy/embryology. They won't know why those molecular trees are consistent with a fossil record unless they understand evolution.

Monday's Molecule #221

Last week's molecule was 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU). It is an intermediate in the degradation pathway from uric acid (or urate) to carbon dioxide and ammonia. Uric acid is the main breakdown product in purine catabolism. Humans have lost activity of all of the enzymes of this pathway so they excrete urate. Most other species excrete ammonia, although in other animals some of the terminal enzymes have been lost.

Some textbooks do not show the uric acid degradation pathway since it doesn't occur in humans and those textbooks aren't interested in an evolutionary approach to biochemistry (e.g. Berg, Tymoczko, and Stryer). The other majors textbooks (Voet & Voet, Garrett & Grisham, Nelson & Cox [Lehinger]) all show uric acid converted directly to allantoin via urate oxidase. This reaction was shown to be incorrect about 15 years ago. The actual pathway from uric acid to allantoin involves two intermediates; 5-hydroxyisourate and OHCU.

Image Credit: Moran, L.A., Horton, H.R., Scrimgeour, K.G., and Perry, M.D. (2012) Principles of Biochemistry 5th ed., Pearson Education Inc. page 568 [Pearson: Principles of Biochemistry 5/E] © 2012 Pearson Education Inc.

The winner, for the second week in a row, is Jean-Marc Neuhaus. [Monday's Molecule #220]. Jean-Marc lives in Switzerland so I've made arrangements to fly over there to visit him and treat him to two fondues at the Pinte de Pierre-à-Bot in Neuchatel. Jean-Marc was kind enough to send me a menu [PDF]. There are about 30 different fondues to choose from. If you would like to join us you can leave a comment on last week's post.

This week's molecule is related to a discussion we are having on the How Do the IDiots Explain the Origin of Life? post. Can you identify this molecule? You have to be very specific.

Email your answer to me at: Monday's Molecule #221. I'll hold off posting your answers for at least 24 hours. The first one with the correct answer wins. I will only post the names of people with mostly correct answers to avoid embarrassment. The winner will be treated to a free lunch.

There could be two winners. If the first correct answer isn't from an undergraduate student then I'll select a second winner from those undergraduates who post the correct answer. You will need to identify yourself as an undergraduate in order to win. (Put "undergraduate" at the bottom of your email message.)

Trace Dominguez of Discovery News Says 98% of Your Genome Is Junk

Theme Genomes & Junk DNAI happened to stumble on this video where Trace Dominguez (@trace501) promotes the idea of junk DNA based on the C-value Paradox—a version of the Onion Test. It's good that he tells the general public about junk DNA but it's bad that he equates "noncoding DNA" with "junk DNA." It's really silly to tell people that the only important part of your genome is the 2% that codes for proteins.

Just so you know, some of the important known functions of "noncoding DNA" are [What's in Your Genome?] ....

1. Genes for functional RNAs like ribosomal RNA, tRNA, and a host of others.
2. Regulatory sequences that control expression of all genes.
3. Part of intron sequences.
4. Origins of replication;specific sites where DNA replication begins.
5. Telomeres.
6. Centromeres.
7. SARS or scaffold attachment regions; sites required to organize chromatin.
8. Functional transposons or "selfish DNA."
9. Functional DNA and RNA viruses.

Scientists believe that about 2% of our genome encodes proteins and about 8% has other functions. It is not true that all noncoding DNA is junk. No knowledgeable scientist ever said that.

I realize that the kind of presentation shown in this video doesn't lend itself to a detailed description of noncoding DNA functions but surely we can do better than this? Why not say that scientists have determined that genes make up about 2% of our genome and about 8% contains information necessary for the proper functioning of genes and chromosomes? The rest, about 90%, is thought to be junk?

98% of your DNA is junk

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How to Turn a Simple Paper into a Scientific Breakthrough: Mention Junk DNA

Attanasio et al. (2013) published a paper in Science where they identified several thousand possible enhancers that were active in the facial area of developing mouse embryos. About 200 of them appear to be controlling genes that determine the size and shape of the face. (Recall that there are about 20,000 protein-encoding genes in mammals.)

Lynn Yarris of Lawrence Berkeley National Laboratory in California (USA) wrote up the press release [What is it About Your Face?]. It's a really good press release that fairly represents the published work and explains some of the significance. There's no mention of junk DNA in the press release or the published paper.

This is what it looks like when science correspondent Alok Jha published it in The Guardian.

Faces are sculpted by 'junk DNA'

Though everybody's face is unique, the actual differences are relatively subtle. What distinguishes us is the exact size and position of things like the nose, forehead or lips. Scientists know that our DNA contains instructions on how to build our faces, but until now they have not known exactly how it accomplishes this.

Visel's team was particularly interested in the portion of the genome that does not encode for proteins – until recently nicknamed "junk" DNA – but which comprises around 98% of our genomes. In experiments using embryonic tissue from mice, where the structures that make up the face are in active development, Visel's team identified more than 4,300 regions of the genome that regulate the behaviour of the specific genes that code for facial features.

It's pretty clear that science correspondent Alok Jha doesn't understand what he's writing and it's about time we started publicizing the names of those science writers who mislead the public about science. The consensus among knowledgeable scientists is that at least 80-90% of our genome is junk. It's time for science writers to admit that the science favors junk.

Scientists have known for decades that a lot of noncoding DNA is functional. The idea that all noncoding DNA (98%) is junk is false. No knowledgeable scientist ever made such a claim. It is a myth perpetuated, in part, by ignorant science writers; albeit, aided and abetted by ignorant scientists. Scientists have known for fifty (50!!) years that gene expression is controlled by regulatory sequences in noncoding DNA. Scientists have known for at least that length of time that during embryogenesis different genes are turned on and off and that this is due, in part, to binding of transcription factors to those regulatory sequences (enhancers). Scientists have known for one hundred years that the morphological features of mammals, including humans, are controlled by genes.

Move along folks. There's nothing to see here.

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Attanasio, C. et al. (2013) Fine Tuning of Craniofacial Morphology by Distant-Acting Enhancers. Science 342: Oct. 25, 2013 [doi: 10.1126/science.1241006]

Oops!

This is the view from the window just outside my office on the fifth floor.

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ASBMB Core Concepts in Biochemistry and Molecular Biology: Matter and Energy Transformation

Theme

Better BiochemistryTansey et al. (2013) have described the five core concepts in biochemistry and molecular biology. These are the fundamental concepts that all biochemistry instructors must teach and all biochemistry students must understand.

The five core concept categories are:

1. evolution [ASBMB Core Concepts in Biochemistry and Molecular Biology: Evolution ]
2. matter and energy transformation [ASBMB Core Concepts in Biochemistry and Molecular Biology: Matter and Energy Transformation]
3. homeostasis [ASBMB Core Concepts in Biochemistry and Molecular Biology: Homeostasis]
4. biological information [ASBMB Core Concepts in Biochemistry and Molecular Biology: Biological Information]
5. macromolecular structure and function [ASBMB Core Concepts in Biochemistry and Molecular Biology: Molecular Structure and Function]

I like the idea of teaching biochemistry from a concept-driven perspective and I like the five categories. However, I was not too pleased with the description of the core concept of evolution [ASBMB Core Concepts in Biochemistry and Molecular Biology: Evolution]. It's one thing to identify the main categories but you also have to get the concepts right if you are going to advocate teaching them!

Let's see how they do with the second core concept.

Matter and Energy Transformation

The Many Forms of Energy Involved in Biological Processes

The energetics of a biological system or process—be it an ecosystem, an organism, a cell, a biochemical reaction—conforms to and is understood in terms of the fundamental laws of thermodynamics. Biological systems capture and process energy from the environment in many forms including that emanating directly from the sun (photons through photosynthesis), heat from the environment (kinetic energy), and energy rich compounds produced by geothermal processes (e.g. sulfur compounds) or other organisms (e.g. carbohydrates). Energy from all sources is chemically converted into useful chemical and physical work in a controlled and regulated fashion. The potential
energy stored in chemical bonds can used to generate motion, light, heat, and electrochemical gradients; likewise, electrochemical gradients can be used to generate motion and new chemical bonds. The input of energy from the environment allows living systems to exist in a state of nonequilibrium with their environment. The discussion of energy and matter conversions in biological systems makes use of the physical concept of changes in Gibbs free energy, or ΔG.

I think we can all agree that a basic understanding of thermodynamics is an important core concept. However, I would have worded this paragraph somewhat differently.

First, I would have mentioned that organisms can capture energy from simple inorganic compounds such as H₂ or those containing Fe²⁺. These are energy sources for many chemoautrophic bacteria. If you are teaching biochemistry from an evolutionary perspective, it's important that students understand how these organisms capture energy. That's the process that is most like the mechanism found in the earliest living cells.¹

Second, I would have put more emphasis on using captured energy in biosynthesis pathways. The paragraph mentions that energy can be used to generate new chemical bonds but that doesn't convey the importance of the process. Think about bacterial cells growing and dividing in the ocean or plants growing from a single seed. Most of the energy goes into making proteins, nucleic acids, lipids, and carbohydrates.

Third, I would drop the reference to cells being in "a state of nonequilibrium with their environment." That conceptt is covered under "homeostasis."

Catalysis

Biologically relevant energy and matter interconversions do not occur rapidly enough (often by many orders of magnitude) to support life. In living systems, biological catalysts called enzymes facilitate these reactions. Enzymes are macromolecules, usually proteins or RNA molecules with a catalytic function. Enzymes do not alter reaction equilibria; instead, they lower the activation barrier of a particular reaction so that reactions proceed much more rapidly. The presence of powerful enzymatic catalysts is one of the key conditions for life itself.

Description of the rates of enzymatic reactions represents the subdiscipline enzyme kinetics. Key concepts of kinetics, including the definitions of the terms v_o, V_max, K_m, and k_cat, constitute a common language for biochemists and molecular biologists in discussing the properties of enzymes.

Students should be able to apply their knowledge of basic chemical thermodynamics to biologically catalyzed systems, quantitatively model how these reactions occur, and calculate kinetic parameters from experimental data.

This is pretty good. I would only add that there are some fundamental concepts of enzyme mechanisms that need to be covered. The idea of a transition state is important. I put a lot of emphasis on oxidation-reduction reactions as a core concept in biochemistry.

Coupling Exergonic and Endergonic Processes

Biochemical systems couple energetically unfavorable reactions with energetically favorable reactions to allow for a wider variety of reactions to proceed.

Students should be able to discuss the concept of Gibbs free energy, and how to apply it to chemical transformations, be able to identify which steps of metabolic pathways are exergonic and which are endergonic and relate the energetics of the reactions to each other.

I have a problem with this section. I don't think that the concepts of "exergonic" and "endergonic" processes are very important in biochemistry and I don't use them in my textbook. They're not found in many other textbooks, either. Also, the idea of "coupled" reactions is very poorly taught in biochemistry courses. It's almost never true that enzymes simply link up two independent reactions, one of which is "favorable" and the other "unfavorable." What usually happens is that a completely new reaction is catalyzed. For example, ATP is not hydrolyzed but, instead, a group transfer reaction is created. This important concept is covered in the next section but the authors do not appear to have grasped its significance.

Not only that, what does it mean to say that a reaction is "energetically unfavorable"? Usually this refers to the standard Gibbs free energy (ΔG°′) but one of the most important concepts in biochemistry is the difference between the standard Gibbs free energy change and the actual Gibbs free energy change (ΔG) inside the cell. In most cases ΔG = 0.

It's true that there are potential "endergonic" reactions occurring inside cells. Think about ATP hydrolysis, for example. The concentration of ATP is maintained at a high level relative to ADP and P_i so the Gibbs free energy change in the direction of hydrolysis is actually more negative that even the standard Gibbs free energy change. What this means is the the reverse reaction is extremely "endergonic."

However, it is simply not true that there are steps in metabolic pathways that are "endergonic" as the authors state. That statement reflects a profound misunderstanding of a fundamental concept in biochemistry. There will not be any flux in the "forward" direction of a metabolic pathway as long as even one reaction is "endergonic." All reactions have to be near-equilibrium reactions or reactions with a negative ΔG that's maintained because the enzyme activity is regulated to prevent the reaction from reaching equilibrium.

The important concept is "flux" or flow of metabolites in one direction along a metabolic pathway. There are many pathways where flux can occur in either direction as in the central part of the gluconeogenesis/glycolysis pathway or the citric acid cycle. Students need to understand what controls flux in one direction or another. They should know that, like water, metabolic flux cannot flow uphill.

The Nature of Biological Energy

In biological systems, chemical energy is stored in molecules with high group transfer potential or strongly negative free energy of hydrolysis or decomposition. These molecules, particularly ATP, provide the free energy to drive otherwise unfavorable biochemical reactions or processes in tightly coupled and highly controlled fashion. Most frequently, the free energy needed for a process or metabolic pathway is provided by group transfer rather than by hydrolysis. In this way, efficient energy transfer is optimized, while inefficient energy transfer to the environment (in the form of heat for example) is minimized.

Students should be able to show how reactions that proceed with large negative changes in free energy can be used to render other biochemical processes more favorable.

The essence of these statements is correct but it is not explained very well. The important concept is not that you "couple" a "favorable" reaction like ATP hydrolysis to an "unfavorable" reaction like synthesis of glutamine from glutamate and ammonia (ΔG°′ = +14 kJ mol^-1).

The point is that the enzyme (glutamine synthetase) catalzyes a completely different reaction—a phosphoryl group transfer reaction—with a negative standard Gibbs free energy change of ΔG°′ = −18 kJ mol^-1.

[see Moran et al. (2011): Introduction to Metabolism]
If there were an enzyme that catalyzed the first reaction involving only glutamate and ammonia then this reaction could easily occur inside the cell in spite of the positive ΔG°′. It would be a near-equilibrium reaction with steady-state equilibrium concentrations of glutamate that were very much higher than the concentration of glutamine.

It's likely that the concentration of glutamine would then be too low to support all the reactions that require it. That's why the reaction involving ATP is more useful. It means that the steady-state concentration of glutamine can be maintained a much higher concentration. This requires regulation of glutamine synthetase in order to prevent the reaction from reaching equilibrium.

It seems to me that the authors (Tansey et al.) have not thought about the fundamental core concepts. They are promoting widespread misconceptions about thermodynamics and metabolism and they are missing some important concepts. I've already mentioned flux. The other missing concept is oxidation-reduction reactions (electron transfer) and the importance of reduction potentials. NADH, NADPH, and QH₂ are important energy currencies inside the cell—just as important as ATP.

There's something seriously wrong with biochemistry teaching if ASBMB educators can't even correctly explain foundational concepts like "evolution" and "matter and energy transformation."

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1. I believe that all introductory biochemistry students should be able to explain where chemoautrophs get their energy. If they can't do it, they haven't been taught the fundamental concepts.

Tansey, J.T., Baird, T., Cox, M.M., Fox, K.M., Knight, J., Sears, D. and Bell, E. (2013) Foundational concepts and underlying theories for majors in “biochemistry and molecular biology”. Biochem. Mol. Biol. Educ., 41:289–296. [doi: 10.1002/bmb.20727]

How Do the IDiots Explain the Origin of Life?

We don't know how life on Earth originated. We're not completely ignorant because we have a good idea of basic biochemistry and we know which enzymes and pathways had to be present in the earliest cells. We're pretty sure that the first life forms captured energy by oxidizing inorganic molecules. We're pretty sure that the first cells formed in the ocean.

We also know from the fossil record that the first organisms were single-celled organisms that resemble modern bacteria in size and shape. We know that they appear more than 3 billion years ago and there were no complex organisms for another billion years. We know that the idea of a primordial soup is nonsense and that speculations about an RNA world are not helpful.

Other than that, all we have is informed speculation. The correct answer to the question of how did life begin is "I don't know."

Denyse O'Leary asks: Origin of life: How are we doing?. She is shocked to learn that scientists have not figured out all the details of how life began. She acts like she knows the answer. She acts like she has an explanation that accounts for all of the data and for the subsequent history of life.

Why isn't she sharing that information? How do the IDiots explain the origin of the first primitive cells more than 3 billion years ago?

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Peter Hess of NCSE Tells Us About How to Make Evolution Compatible with Christianity

Minda Berbeco once taught evolution and she was surprised that her students wanted to talk about religion. She decided to consult with Peter Hess, the director of religious community outreach at the National Center for Science Education (NCSE). Her blog post is on the NCSE website at: When Students Ask about Religion.

Peter Hess mentioned that many people see a conflict between science and religion so Minda asked him what she should say to such people. Hess replied ...

I would recommend citing examples from the numerous scientists who have integrated current science into their religious worldviews, scientists such as Kenneth Miller, Francis Collins, Robert Russell, and Father George Coyne.

Another tack would be to cite statements from theological figures, such as Pope Benedict’s statement in Communion and Stewardship (2002), when he was still Cardinal Ratzinger:

Converging evidence from many studies in the physical and biological sciences furnishes mounting support for some theory of evolution to account for the development and diversification of life on earth, while controversy continues over the pace and mechanisms of evolution. While the story of human origins is complex and subject to revision, physical anthropology and molecular biology combine to make a convincing case for the origin of the human species in Africa about 150,000 years ago in a humanoid population of common genetic lineage.

Let me be clear: I’m not suggesting that you cite the views of such scientists and theologians as authoritative. There’s a wide range of religious reactions to evolution, from rejection to embrace, and you may not feel comfortable in endorsing any of them. (Indeed, a teacher in the public schools is required not to endorse any of them in the classroom.) But many people who reject evolution for religious reasons are ignorant about, or have never been seriously exposed to, the range of religious reactions to evolution. It may come as a complete surprise to them that devout religious people—perhaps even people of the same faith—have no theological objection to evolution. And opening people’s horizons is part of what education is all about, isn’t it?

There's so much wrong with this advice that I hardly know where to begin.

First, Hess seems to assume that Minda Berbeco is a Christian because otherwise his advice makes no sense. Surely, he wouldn't expect an atheist like me to tell students that the Pope is an authority on evolution? What if the teacher is a Muslim, a Buddhist, or a Hindu? What should they say? (Peter Hess is Roman Catholic.)

Second, he says that the views of these scientists (and the Pope) should not be cited as authoritative but if he really believes that then why cite them at all? Why not cite those religious scientists who think there really is a conflict between evolution and their religious beliefs?

Third, just because some scientists have been able to rationalize their acceptance of evolution with their Christian beliefs does not mean that there's no conflict. That is not a very good way to teach students how to think critically. After all, there are scientists who believe in homeopathy and astrology but that doesn't mean there's no conflict between real science and those pseudosciences, does it?

Fourthly, I agree that opening people's horizons is an important part of education. That's why I would tell students that, yes, there is a very real conflict between science and religion. It's quite likely that your faith will be severely challenged if you learn about evolution and science. Many students have never been seriously exposed to the atheist position. Somehow I don't think that's what Peter Hess has in mind when he talks about "opening people’s horizons."

Peter Hess recommends that students visit the Christian accommodationist webpages on the NCSE website [Science and Religion]. So, fifthly, I recommend that NCSE offer a more balanced view of this issue where they point out that there are many scientists who believe the conflict is very real. (I would be happy to write something.) NCSE should also expand their discussion to include non-Christian views of evolution.

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