I was NOT "underwhelmed" by Live Earth, were you?

On Monday, July 9, the Environmental News Network ran a story examining the global concert event for climate change awareness--Live Earth--led by former Vice-President Al Gore, which took place this past weekend.


Their review was less than stellar, claiming that Live Earth "rocked the world" but did nothing to change it. What did they intend to leave us thinking or feeling after scrutinizing the overall low intensity news response, the choice of Madonna as a participant, and the difficulty of mixing music with real problems and important causes in the world? Basically, nothing, except the cheerful news they thought Live Earth was a dismal failure but Germans were happy with Snoop Dogg. That ain't much to offer.


So, I don't know if anybody reads what I write, but like everyone else blogging, I'll be squeezing off my two cents worth.


First and foremost, Live Earth was awesome. It was awesome to see some action, to see steps taken to highlight a real problem and seek support for a solution. A Darwinian view of life is a rational and humanistic view, a view which prizes philosophical morality and is sensitive to moral philosophies about how we live our lives with respect to the biosphere. This means that moral (understood to also be educated) Darwinians support the logical and personal decision to be conscientious and supportive of environmental issues like climate change. For a serious scientist who reads and teaches about conservation, and one who recycles excess paper and comingled recycles every day and is mindful of his carbon footprint, seeing somebody get out there and raise awareness about this problem and do something about it, not just talk about it, was a rare and beautiful event.


The second reason I view Live Earth as a success is that it brought a relevant message in a relevant format. That speaks success to me. Young people showed up, in case you didn't notice. The celebrity status of the performers was a good thing, an eye-catching and inviting piece of the puzzle, not something that reduced the credibility of Live Earth. Criticizing the concert series only underscores a critics unique position to bad mouth. It's an easy out. The environmental philosophy (or lack thereof) of the performers has absolutely no impact on the credibility of the message of LE. The truth is that Live Earth was relevant. I am proof of that.


I was able to watch Live Earth via the internet. Including myself, approximately 2 billion people are thought to have witnessed the event. I sang along with Bon Jovi and Jack Johnson, and that's not all. Ultimately, I felt a deep connection with hundreds of thousands of strangers who (a) enjoy good music and (b) showed up for an event that supported an arm of the environmental movement. Undoubtedly, even more have heard about the event orally or by way of other forms of advertisement than was reported. Wasn't your passion ignited as well? Weren't you moved by the show of support? If so, your duty is action. Based on the reviews, if you thought Live Earth was productive, you need to stand up and say so. If not, like the ENN folks, then I would be willing to accept skepticism, but barring it from the logic, I would only be willing to call into suspicion the integrity of your environmentalism. And that's ok. You're just immoral or illogical, a fool either way.

The Cell Cycle

Multicellular eukaryotes that reproduce via sexual reproduction present a case we are all familiar with. During or after sexual contact, gametes fuse to form a zygote, a single cell containing hereditary material from each parent. This description represents only a small snapshot of eukaryotic life, with a couple frames following fertilization thrown in for free. We may reason about this relatively singular event series and its importance, but we cannot help noticing more than the most basic case, two separate entities gave rise to one new entity, just happened. In particular, we know that the individual gametes must have had different qualities and different origins, and furthermore the zygote goes on to become orders of magnitude larger and more complex. In this post, I will briefly summarize the roles of cellular division in gamete development and human physiology and review the cell cycle and its regulation. I then will conclude with some comments about evolution as it relates to this topic.

Despite the lopsidedness of the introductory example, cell division is integral to the evolution and life of single-celled and multicellular life. The purpose of cell division in single-celled organisms is to duplicate the whole individual! In complex multicellular life forms, such as Homo sapiens, serial cellular divisions and differentiation give rise to extraordinary physiology from single-celled starting material. Also in humans, cell division occurs to regenerate certain tissues hence organs that degrade through time. Among these are our red blood cells, skin, hair, and certain glands. Many interesting factoids have been quipped about estimates of turnover during this process and other interesting phenomena. Check a couple out here and here. Most of my discussion will focus on eukaryotic cells and attempt to avoid these.

Dividing cells spend their time in one of two states, (1) Interphase (growth and duplication) and (2) mitosis (splitting into two new cells). These two processes can be broken down into a series of smaller phases. Overall, the cell cycle, or cell division cycle or however it may be called, always involves the following phases in sequential order under normal conditions: G1 phase, S phase, G2 phase, and mitosis. Here, G stands for "gap" so that G1 means "gap" 1, S stands for "synthesis," and G2 refers to "gap" 2. Beyond these, mitosis is traditionally split into several phases, itself. These, also in sequence, are termed (a) prophase, (b) prometaphase, (c) metaphase, (d) anaphase, and (e) telophase + cytokinesis. New cells formed during mitosis are called daughter cells. This early institution of organization may be helpful. On the contrary, you may be asking what I first asked when I heard these terms for the first time, "What does all this mean?" Discussing the cell ultrastructure involved often helps alleviate this pain. This will be touched on after describing the cell cycle.

While there are distinct phases of the cell cycle, all three non-mitotic phases are similar; in each, the cell grows as it duplicates chemicals, organelles and proteins. The S phase is unique, because it is the phase where DNA is duplicated. Interestingly, the S phase is considered the longest phase of the cell cycle, filling about half the total amount of time necessary for average human cell division (Campbell and Reece 2005).

Cell Cycle Regulation (van den Heuvel 2005; Campbell and Reece 2005; others)

The cell cycle is controlled by several different types of membrane-bound enzymes and other factors conserved (i.e., found) in most dividing animal cells. Studies indicate major importance of three or four different kinds of kinases and other genes in this mosaic of regulatory pathways. Also, the cell cycle may be controlled by extrinsic or intrinsic factors. Generally, external signals only regulate whether or not animal cells reproduce up to a point called the restriction point or G1 checkpoint. On the other hand, a number of important internal factors regulate the cell cycle intrinsically from this point.

The main paradigm of cell cycle control is one of activation-inactivation cycles generated by changes in the amounts of regulatory factors, cyclins and kinases. Kinases "activate" or "inactivate" different proteins controlling cell division by substrate-level phosphorylation at checkpoints such as the restriction point. Kinases themselves may also exist in active or inactive states corresponding to their position with respect to cyclins. Activated and inactivated kinases are attached or unattached to cyclins, respectively. This is why these kinases are called cyclin-dependent kinases, CDKs. As cyclins increase and decrease in thier relative concentrations in the cell (and CDKs remain relatively constantly concentrated), CDK activity changes disproportionately, with activity increasing abruptly after gap 2 then falling as cyclin is degraded during mitosis. Actually, synthesis of cyclins occurs from S phase through gap 2 phase. While cyclins are degraded, CDKs are thought to be recycled during this process. So, why is this a regulatory pathway anyway? Because without cyclin accumulation, mitosis is not signaled. An important CDK complex called "M-phase promoting factor" signals spindle formation, nuclear envelope breakdown, and chromosome condensing. Without these, M phase, thus the cell cycle, would never be completed.

Mitosis

As I mentioned in an earlier post, DNA (of eukaryotes) is housed within the nuclei in the form of a substance called chromatin, in which histone proteins and tangled nucleotide strands are incorporated together. This chromatin is loosely distributed in long thin fibers. During S phase all the genetic material replicates itself, but chromatin is still in loose form. Later, during mitosis, the chromosomes condense and the cell actually divides. A unique set of machinery is involved in these processes. Most notably, cytoskeletal structures provide substrates (analogous to small roads or steady surfaces in the cell) for chromosomes to be transported along by motor proteins; also, centromeres play a pivotal role. Perhaps the best way to describe mitosis is the common way, or detailing the events at each phase of the process.

Prophase: The prefix pro- means this stage is "before, or preceding" the following other phases of mitosis. During prophase, chromatin is condensed into recognizable chromosomes. Originally, these were single units. After duplication and condensation they represent a pair, each called sister chromatids of the other. At the center of these chromatids is a region known as the centromere, which connects the chromatids, or copies of the original DNA molecule. Tan cuidado! The centrosome-centromere problem may confuse you. At the same time these chromatids assemble, the centrosomes begin sending out microtubules, which push the centrosomes farther apart by physical force.

Prometaphase: Here, the prefix meta- means "growth" or "unification, or important" phase, so this phase precedes the really unifying step. Prometaphase includes breakdown of the nuclear envelope (microfilaments and pore complexes), which degrade substantially to clear space for metaphase and anaphase. Also, the staging of the microtubules becomes much more complex, extending across the cell to connect with special structures formed at the centromeres, called kinetochores. Kinetochores are specialized proteins. There is a name for microtubules which are now very obvious in the cell--they're called spindles. Some spindles connect with kinteochores, others connect with other spindles across the cell.

Metaphase: Metaphase is one of the most time consuming and important phases of mitosis. During this time, chromosomes are aligned on a plane bisecting the distance between the centrosomes, which is termed the metaphase plate. It's not a real plate or plane, but rather an imaginary one. Microtubule spindles attach at kinetochores closest to them such that chromosomes line up with kinetochores facing each pole of the cell signified by centrosome position.

Anaphase: Ana- means "true" or "original." However true or original this step is, a fact is that it's the shortest phase of normal mitosis. It is during anaphase that the chromatids are ripped apart from one another by the microtubules, thus taken to their respective poles of the cell. For some reason--ah, because the end products are called daughter cells--the chromatids become called daughter chromosomes after this point. Remeber the spindles that hooked up with one another, not the kinetochores? At this point, those push off one another to help distance the chromosomes and increase the distance between the poles of the cell.

Telophase + Cytokinesis: Finally, telophase unites the genetic material of each daughter cell into an enclosed nucleus while cytokinesis splits the cytoplasm via invagination of the plasma membrane (involving microfilaments) and segregation of the fluid matrix making up the innermost cellular space. And mitosis is over, just like that. You can remember the order of these phases by memorizing the names, memorizing the prefix meanings, and or memorizing the order like this P2MAT.

Cell division from the standpoint of evolution and disease

According to Campbell and Reece (2005), "As eukaryotes evolved, along with their larger genomes and nuclear envelopes, the ancestral process of binary fission [bacterial division] somehow gave rise to mitosis." Researchers have actively been seeking answers to persistent questions about the mechanisms involved in mitosis. This work has included plants, many of which reproduce asexually through mitotic cell-lineages (Fagerstrom et al. 1998), as well as diatoms and bacteria.

Save the best for last. That ability is one of the greatest given to the human condition, and exactly what I think I've done waiting to talk about the coolest parts of the cell cycle, apoptosis and disease! Trust me on this one.

Scientists' understanding of CDKs' functions in cell cycle regulation and their interactions with other chemicals are just beginning to be explored. We have discussed what we know about what happens when things go right in cell cycling, but what about what we know about what happens when things go awry? For me, this was one of the most interesting and exciting facets of my introductory cell biology class. I hope your decision about which part of the cell cycle and its regulation, like mine, hinges upon the next few pieces of information.

If S phase replication goes wrong and DNA is damaged, this can have negative effects. So, cells halt the cell cycle by slipping into "gap zero" phase, or G0, while damaged components are repaired. Also, it is integral that mitotic spindle fibers attached to kinetochores, and the right ones at that. So, cells can halt motion to the next phase of the cycle in the even this happens. HOWEVER, if things don't get fixed or something else dysfunctions at these crucial times, the cell may induce suicide, or apoptosis (a.k.a., "programmed cell death").

An important gene regulating both of these processes is p53. p53 is in a special group of tumor suppressor genes, which keep the cell from slipping into cancerous states. Of course, I haven't talked about cancer. So, what I mean is that if things go awry (e.g., if DNA is damaged by an environmental factor instigated by a physical action, such as smoking), the cell may never be able to turn off (step into gap zero states or die via apoptosis), thus it may continue dividing infinitely with misreplicated genetic information. Cells in this state cause cancer by creating many clones of themselves (a tumor), which are harmful to the body because they fail to recognize tissue boundaries and may travel to other areas of the body, depleting normal tissues. p53 blocks the cell cycle by inactivating CDKs and has the power to induce programmed cell death in abnormal cells. WHEN p53 is doubly recessive (mutant), these functions are not carried out and cancer will develop beginning, perhaps, with a single damaged cell.

A report on wikipedia.com resounds a common statistic, that cancer is responsible for approximately 10-20% (13%) of all human deaths. In this way, we see that the cell cycle is not only important to our growth and complexity, but also that factors along the way play a critical role influencing our health and well-being. Similarly, mistakes during mitosis result in genetic variation among individual offspring of parents, ensuring natural selection has lots of material to work with in healthy populations. Now that you know so much about a process that led to your diversity and uniqueness, watch this time-lapse video of cell division!

References:

van den Heuvel, S. Cell-cycle regulation (September 21, 2005), WormBook, ed. The C. elegans Research Community, WormBook,
doi/10.1895/wormbook.1.28.1, http://www.wormbook.org.

Consumer Reports: My Energy Comes from Plants?

A "Consumer" Report

Ladies and gentlemen, we are consumers. Newsflash! I know, I know... it's America. Capitalism, materialism... these are familiar concepts. But I'm a biologist. It's what I do (observe the world around me critically). And lately I've been thinking about consuming in a biological context. Surprise, surprise. Recall, I've been using this blog to refresh readers (and myself) about the basics of biological science (click here to see where this started). Consumer Reports is a popular magazine complex interested in reviewing and rating products in hopes of helping consumers make smart buying decisions in the American (and global) marketplace. Today, I'll be submitting my own Consumer Report. This report, however, focuses on the underlying biological mechanisms--those relating to photosynthesis--responsible for the energy in what we consume. As always, I will attempt to paint a picture of photosynthesis from an evolutionary perspective.

You and I consume other living things, from which we obtain energy in a variety of different forms, mostly as proteins, lipids, and long chains of sugars called carbohydrates. As I have just discussed (last couple of posts), our bodies are made of millions and millions of cells capable of using energy bound up in the foods we eat after converting it to energetic currency called ATP through the processes of glycolysis and cellular respiration (if oxygen is present in our cells). But we never serve as the origin of any energy we use.

While our bodies can transform basic chemical compounds into more complex and useful forms (e.g., 10 of the essential amino acids used to synthesize proteins), we are constantly converting energy from one form to another (remember that first law of thermodynamics?). The question eventually arises, where does all this energy come from in the first place? The short answer isn't found on mother earth. It's the sun. A more fruitful explanation lies in the study of plants and other organisms (cyanobacteria, green algae), which we call autotrophs or producers, which can convert solar energy into chemical energy.

Evolution and Photosynthesis

First, a little digression... Evolutionary biologists (like myself) are scientists interested in all aspects of the evolution of biological species. While most evolutionary biologists do not concern themselves with the origins of life, other scientists' work often focuses on evaluating and empirically testing the significance of other kinds of evidence (i.e., astronomy, geology, early earth biochemistry, et cetera) about the archaeology of early life and the ancient earth environment. Sometimes scientists intend to demonstrate the validity of different theories about these latter phenomena, while at other times scientists make discoveries with implications for how we think about the history of life, while this was not their original intent; this second class of discoverers simply realize the implications of their new knowledge after laying it bare. Because photosynthesis is thought to have played a pivotal role in the evolution of life on earth, I choose this perspective as my starting point.

Isotopic studies of meteorite tungsten demonstrate confirm the long-held and well-supported idea that the earth is very, very old--around 4.6 billion years, give or take 10 million, to be more precise (Jacobsen 2003). Evidence suggests simple prokaryotic cells evolved between 3 and 4 billion years ago (Line 2001). Later, the processes of life's evolution generated single celled eukaryotes just over 2 billion years ago, which were first very simple then engulfed proto-plastids and evolved into photosynthesizing eukaryotes (as described in an earlier post, which you can read here) (Margulis 1970; Campbell and Reece 2005). Because a by-product of photosynthesis is oxygen, these creatures, which increased exponentially in number, played a major role in setting the environment up for more complex lifeforms (i.e., animals and land-dwelling plants) by increasing the atmospheric and aquatic O2 concentrations of the early earth (Dismukes et al. 2001; Campbell and Reece 2005). Recently, molecular sequence data of cyanobacteria chloroplasts are consistent with these other findings in demonstrating an ancient origin of photosynthesizing cells (Xiong et al. 2000). Not surprisingly, photosynthesis is still generating crucial oxygen used by most species today. Now that you know a bit about the evolutionary significance of photosynthesizing organisms. Thus, we turn to the process of photosynthesis itself.

Photosynthesis

Everyone who knows anything about this important process knows photosynthesis occurs in plants. Those more erudite scholars among you might even know this happens, more specifically, in the chloroplasts evolved from early plastids I mentioned. Those with heads high in the heavens (even concocting a nosebleed) of scientific knowledge might even remember that plant chloroplasts are divided into different parts and that different sub-cellular pathways carry out what are call "light" and "dark" reactions, that there are different photosystems, and or that electrons are involved in chemiosmosis during the sequence of super duper photosynthetic events. Allow me to clarify for those of us who aren't as smart as the nosebleeders.

Chloroplast Ultrastructure

Chloroplasts, like mitochondria, have two outer layers--outer and inner membranes--and are filled with interconnected networks of membranous sacs known as thylakoids. Chlorophyll is a special pigment in thylakoid membranes that give plants their green color, as you shall see.

As I mentioned, photosynthesis involves two different phases. These are the light reactions and the Calvin cycle. These are crucial to your life and mine and to life's evolution.

Light Reactions use solar radiation to convert carbon dioxide and water into useable chemical forms

Generally, light reactions convert solar energy into chemical energy trapped in the form of ATP and an electron carrier, NADPH (similar to NADH and FADH, from discussion of cellular respiration). By solar energy, I mean light. Let me explain. Light is electromagnetic radiation or energy travelling in the form of waves with the properties of particle packages of energy, or photons. Different wavelengths of light are visible and invisible (see electromagnetic spectrum). Light with low wavelengths is intense (has more energy; e.g., violet light) while the converse is true of long wavelength light (e.g., red light). When light from the sun (which emits all wavelengths of light) hits objects on earth (mostly visible light reaches the surface), some visible light is reflected by those objects, which may absorb or transmit (allow to pass through them) other wavelengths. Chemicals called pigments absorb many frequencies of visible light and reflect a narrow range of wavelengths. So, we see that the chemical composition of matter is highly variable, thus objects take on different colors because their pigments or absorption characteristics (absorption spectra) allow only certain colors to be reflect and processed by visual sensory organs of living things, (e.g., our eyes). And that's a simple (albeit incomplete) explanation of why we perceive objects to be different, specific colors!! Isn't that cool? Nonetheless, there are deeper truths these facts hold in store for photosynthesis.

Thylakoid membranes are peppered with chemical complexes called photosystems. In broad terms, photosystems consist of chemical complexes (groups of large molecules) containing photosynthetically important plant pigments (which I expand on later) surrounding a central region where special pigment molecules are housed. The light reactions of photosynthesis depend upon the excitation of electrons in photosystems and the transport of these electrons down protein chains to generate energy bound in ATP and NADPH.

To elaborate, there are two photosystems at work in plant cells, photosystem I and photosystem II. Here's how they do the work of the light reactions. Pigments in photosystem II abosorb light from the sun at wavelengths of 410-510 nm and 610-700 nm (both are approximations). This light is in the form of an individual photon which energetically must exactly match the difference between excited electron states and the ground state of the pigment molecule (most commonly discussed are chlorophyll a, chlorophyll b, and carotenoids). The photon's energy is transferred directly between pigment molecules in photosystem I's outer complex until it reaches the base of the inner region, where two special chlorophyll molecules are located. These molecules, because they absorb light best at 680 nm, are termed P680's. Absorption of the photon powers a single electron from one of the P680's to a higher energy state, a higher orbital (if you know chemistry). The excited electron reduces a molecule called the primary electron acceptor. Nearby, an enzyme quickly breaks a proximate water molecule into its constituent parts: oxygen, two protons (H+), and two electrons. The electrons drop back to each fill the void left in each P680 molecule at the base of the inner photosystem region from giving electrons to the primary electron acceptor. (hang with me here!) Next, the primary acceptor drops its newly gained electron in one of two places, electron transport chains (ETC; we'll call them electron transport chains one and two, ETC1 and ETC2!). For now, we consider what happens down each individual ETC.

ETC1 is similar to the ETC found in mitochondria, which functions in cellular respiration. As with mitochondrial ETCs, ETC1 breaks the explosive change in energetic state of the electrons from photosystem I into a small series of steps, each yielding ATP. Eventually (quickly), our little electron is passed to photosystem I. That's right! Electrons go from photosystem II to photosystem I. Kind of weird, huh? The explanation for this apparent misnomer is that the photosystems were named in order of discovery, with scientists later determining the order of electron passage contradicted the nomenclature.

The last compound in ETC1 drops our electron directly onto the special pigment molecules called P700's, chlorophylls that absorb light best at 700 nm (go figure), which are at the base of the central region of photosystem I. Again, this transfer of energy blasts electrons from P700's to an excited state, which reduces photosystem I's primary electron acceptor. This acceptor, in turn, drops the electron down the other ETC (i.e., ETC2), where, upon reaching the bottom of the chain, it is passed on to an enzyme called NADP+ reductase. This enzyme requires two electrons from the light reactions (photosystem I) to reduce NADP+ to NADPH, an electron carrier molecule. And that's it for the light reaction phase!

ATP generation

I told you that electrons dropping down ETC1 make ATP and those funneled down ETC2 cause NADP+ to be reduced to NADPH. What I said was true. However, I was holding something back; namely, the mechanism responsible for these changes. It is a familiar mechanism, chemiosmosis (if you don't know what this means, read this)! This is the same mechanism driving the generation of the majority of ATP in aerobically respiring living cells, oxidative phosphorylation, a process of cellular respiration.

As I have stressed in talking about cellular respiration, ATP is generated by an enzyme, ATP synthase, as a result of a H+ gradient in mitochondria. The same is true of photosynthesis. In mitochondria, ATP is made as H+ are pumped down their concentration gradient from the mitochondrial intermembrane space into the inner space of the organelle (mitochondrial matrix), where ADP is phosphorylated into ATP. In plants, things are not much different. Obviously, the electron transport chains are different. Less obviously, however, is the fact that another similarity exists. In mitochondria AND thylakoids, the ETC's and ATP synthases are embedded in the same membrane (the inner membrane of mitochondria, the only membrane in thylakoids) and ETCs supply force to pump H+ into a different space (against their passive transport directionality, therefore requiring active transport) which accumulate and run easily through ATP synthase literally turning the machinery to generate energy for ATP production. Whew! Clear as mud right? But where does that ATP go next? How is it actually used in cells of plants? What kind of work do these cells accomplish and why is it important to you and me as consumers? Simple (ha ha).

The Calvin Cycle

In brief, the Calvin cycle uses ATP and NADPH to turn carbon dioxide into polysaccharides that benefit consumers like us! In a sense, this process is partially analogous to a reversal of the citric acid cycle (CAC). On the one hand, the CAC uses oxidized sugars to generate chemicals storing energy. On the other hand, the Calvin cycle expends energy to make sugars, which are stored in plant tissues and consumed by animals as food. The Calvin cycle is comprised of three phases, (1) carbon fixation, (2) reduction, and (3) regeneration of the starting materials (carbon dioxide). While some think of the Calvin cycle as generating sugars directly, this is not the case. Instead, it yields three carbon sugars which are also intermediates in CAC's, glyceraldehyde-3-phosphate, or G3P. Enzymes separate from the Calvin cycle use G3P as a starting material for glucose genesis, which only involves a few steps.

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Dismukes, et al. 2001. The origin of atmospheric oxygen on earth: the innovation of oxygenic photosynthesis. PNAS 98(5):2170-2175.

Jacobsen, S.B. 2003. How Old Is Planet Earth? Science (Washington). 300(5625):1513-1514..

Line, M.A. 2001. The enigma of the origin of life and its timing. Microbiology 148:21-27.

Margulis, L. 1970. Origin of eukaryotic cells. New Haven, Yale University Press.

Xiong, et al. 2000. Molecular evidence for the early evolution of photosynthesis. Science 289(5485):1724 - 1730.

For info on other citations, see References post.

References

This post will be an on-going list of some sources I reference frequently or which are integral to a lot of stuff I review here about basic biology. Those include:

Campbell, N. A., and J. B. Reece. 2005. Biology. 7th Edition. Benjamin Cummings: Boston, MA.

Wilson, E. O. 2006. The creation: an appeal to save life on earth. W. W. Norton & Company: New York, NY.

Cellular Respiration: Brief Look at the Citric Acid and Oxidative Phosphorylation

Just recently, I blabbed about cells and cellular respiration. Then toward the end of my last post I got really excited about cellular respiration as fundamental to all living creatures, including you and me. But all I had really talked about was the fundamental units of biological organization, the smallest living things, thermodynamics and biological chemistry, and how we get a little ATP and a bunch of energy stored as pyruvate from each glucose molecule that gets broken by glycolysis. Nothing very important, really...

Perhaps you remembered vaguely when you first learned this material. Perhaps you wondered why anyone would care. Perhaps you were amazed to be reminded of the chemical basis of all life on earth, the far-reaching implications of the chemistry which forms the foundation of biological science. If you're in the latter group, right on! And read on! Because glycolysis is only one process linked to cellular respiration. It is not considered a part of real respiration because oxygen is not involved. And it yields a relatively small amount of ATP dividends per unit starting molecule and per unit effort (10 steps, two molecules of ATP burnt off). What really gets my engine burning, and hopefully yours too, are the citric acid cycle (CAC) and oxidative phosphorylation (OP).

Before I talk about these, allow me to just say that these aren't just singular discoveries written down in books so that students get a view of the big picture from their biology education--at least, that's not all these are. Instead, the CAC and OP pathways represent active areas of scientific research. Recent studies illustrate this point: a group of scientists from Germany and other places have been looking into fluorescent imaging of CAC intermediates (here), while American scientists have examined the origin and self-organization of biochemical cycles, not to mention the evolution of the enzymes involved.

So, on to CAC and OP and what these should mean to you and me.

The CAC (Fig. 1 below) is an eight-step biochemical pathway turning pre-packaged Acetyl-CoA (a modified form of pyruvate from glycolysis; two per glucose molecule, just like pyruvate) into two molecules of CO2, three NADH, one ATP, and one FADH2 (an electron carrier similar to NADH). On the other hand, OP takes electrons from NADH and FADH2 made available from glycolysis and the citric acid cycle and uses these to generate up to 32 or 34 molecules of ATP per starting molecule of glucose!!! As an aside for now, Acetyl-CoA used in the CAC may also come from proteins and lipids--not just glucose--but this is beyond the scope of our discussion. All in all, factoring in CAC and OP in view of the classical glucose metabolism perspective, each molecule of glucose broken down in your cells has the potential to generate up to 36 or 38 molecules of ATP!!!


Figure 1. The citric acid cycle (Orgel 2000, see link at end of text).



So, we see from this overview how oxidative phosphorylation and chemiosmosis (linked processes) are together responsible for the majority of ATP produced by the respiration of our cells (eventually linked to the respiration we do with our circulatory system and respiratory systems, or blood and lungs). These ATP generated by OP and chemiosmosis are largely the result of what is known as the electron transport chain (ETC), making this one of the most important sub-cellular structures in living things.

The ETC is a collection of multiprotein complexes found all over the inner membrane of our mitochondria. NADH and FADH2 deliver electrons to specific pieces of this chain. In turn, these electrons move down the chain using well-known avenues. At the end of this chain, the last protein in the ETC sequence (these proteins are mostly particular kinds, called cytochromes. My DNA Barcoding work studies cytochrome oxidase 1 to explore nearshore fishes of the Carribbean/Western Central Atlantic for cryptic speciation events), "Cyt a3," transfers its electrons to oxygen (O2), which grabs two hydrogens to become water (H2O). Because electrons from FADH enter the ETC at a different protein complex than those donated by NADH, they provide less energy for ATP synthesis than those from NADH.

So, electrons release energy as they fall down the ETC. "But how is this energy harnessed to make ATP?" you might ask. Simple. Coupling electron transport to ATP synthesis (exergonic reactions coupled to endergonic ones, as mentioned elsewhere). This is accomplished by the process of chemiosmosis.

Chemiosmosis is the phenomenon whereby motion of an ion across its gradient through a membrane releases energy which is used to do cellular work. ATP synthase, also found in the inner wall of the mitochondrion, is the enzyme responsible for ATP formation from ADP (the "used up" form of ATP in our cells) and inorganic phosphate (P-). In the case of ATP synthase, the ion used to generate the energy of ATP regeneration is hydrogen, which accumulates in the mitochondrial intermembrane space as a result of the action of the ETC. This combined action of the ETC and chemiosmosis make up what we know as oxidative phosphorylation, what I have called OP. One key difference between this process and the ATP-yielding pathways we've discussed, glycolysis and the citric acid cycle, is that OP generates ATP from phosphorylation using these two processes instead of substrate-level phosphorylation, the method of glycolysis and CAC. Are you with me??

Hope so.


There you have it... in a nutshell, the difference between glycolysis and cellular respiration, the difference between glycolysis/CAC and oxidative phosphorylation (ETC + chemiosmosis/ATP synthesis), and all fit into an overview of how we get chemical energy from our food. Holla!

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See Campbell and Reece (2007) for more information, or try a search of Google Scholar to learn more about cellular respiration, glycolysis, the CAC or OP. Or, read this Orgel (2000) paper. Peace out ~ JB

Cellular Respiration: Cells, Energy and Glycolysis

Living cells perform work. Essentially, work is the amount of energy transferred by force, thus energy is required for work to take place. My fingers are performing work by pressing down on and transferring their kinetic energy to the keys on this keypad. This is a coordinated effort of nervous impulses in my brain receiving and dictating signals to and from the muscles and other tissues of my eyes, hands, and fingers. An input of energy is required for each type of tissue involved to accomplish the task of each keystroke. My brain cells are not performing the same type of mechanical work as my hands and fingers; however, they are costing my body an enormous amount of energy through maintenance and metabolic costs from not only my mental activity, but also the basic needs of my neural cells. Recall how two major themes of biological science are (a) that energy flows through ecosystems from the sun to producers to consumers and (b) that living things place energetic demands on their environments in order to do the work characteristic of life. At this point, we will delve into these in greater detail, all from the standpoint of cellular respiration.

Cellular respiration (CR) might be defined as the sum of all the processes involved in the catabolism (breakdown) of food molecules (protein, carbohydrates, and lipids) into carbon dioxide, water, and energy bound in the form of ATP and heat released from chemical reactions involved. This relationship between different chemical and physical variables of cellular respiration is similar to the oxidation reactions generating motion in heat combustion engines. A major goal of any education in cellular respiration should be founded upon an understanding of the way cells arrive at ATP and the way this molecule is utilized by cells to supply the energy necessary for life. Before this can be grasped, however, it is necessary we embellish more on the nature of energy and metabolism in natural systems.

The first law of thermodynamics: Energy is neither created nor destroyed, it may only be transformed or transferred from one form to another. Second law of thermodynamics: all energy transformations and transferences increase the overall entropy of the universe. Notice how this second law of thermodynamics need not apply to individual transactions between organisms and their environment, whether the events we consider are single physical interactions of adults or we are concerned with development or evolution of populations. What I mean by this is that, simply, we learn from studying nature how many ordered phenomena coexist with random, chaotic, or stochastic processes and events. The order we find in the universe, in the beauty and symmetry of life or its evolution for example, does not contradict the second law of thermodynamics because these are single occurrences while organisms and their populations increase the entropy of the universe in other ways, including heat loss. Thus, while individual structures or events may decrease the entropy of the universe (by introducing orderliness; e.g., cleaning your room), the universe is more than its individual systems (organisms, ecosystems, planets, etc.), extending to includes each system’s surroundings (e.g., where heat is lost), so entropy may drop locally but is always increasing in the universe as a whole.

The Gibbs free energy (ΔG) of a system describes the energy available for work in a system, such as a cell, when pressure and temperature are constant. This quantity is equivalent to the total energy in a biological system minus the entropy change over a given time period at a given temperature. Spontaneous processes use available energy and in doing so decrease the energy in a system, and therefore are represented by negative Gibbs free energy values; conversely, a positive value of ΔG suggests a process is not spontaneous. Systems in the biosphere often run down energy gradients towards energetically more stable states, the most stable of these being that of equilibrium, where free energy change is near zero or positive and more work cannot be accomplished. Our cells represent dynamic systems where many different types of chemical and mechanical forces are at work to maintain and alter living things. Here, in our cells, reactions where energy is lost (ΔG <> 0), or endergonic reactions, may occur, often in simul. Because of the many chemical processes carried out in our cells, our bodies never reach a state of energetic equilibrium; rather, materials constantly flow through our physiological systems.

Biologists generally recognize three kinds of work cells accomplish using the energy harvested from biochemical reactions making up cellular respiration (oxidizing food particles into useful energy), (1) mechanical work involving movement of various cellular structures, (2) transport work which pumps substances across membranes against concentration gradients, and (3) chemical work, which involves supplying energy from outside of chemical products to force processes to completion which are not naturally spontaneous. Much of this work is accomplished through energy coupling, or using exergonic processes to generate energy fueling endergonic processes. I have already commented on the role of mitochondria in ATP production, the ability of this molecule to trap energy, and subsequently have alluded to its importance in cellular respiration and metabolism. But what is the structure and importance of ATP really like? Why, more specifically, is its role in the reactions of cellular respiration important, and what are those reactions themselves like?

Each ATP (adenosine triphosphate) molecule is composed of a nitrogenous base, adenine, linked to a ribose (pentose, or five-carbon ring structured) sugar, which is in turn connected to three inorganic phosphate molecules. The region of ATP containing these inorganic phosphate molecules is negatively charged and unstable, making ATP an effective reducing agent (it oxidizes other molecules). When bonds between ATP phosphates are broken by hydrolysis in our cells by enzymes, a P group is transferred to other molecules, which are then said to have been “phosphorylated” by ATP, which is oxidized to ADP, adenosine diphosphate. This process of phosphorylation represents a coupling of exergonic (ATP hydrolysis) and endergonic processes used by the cell to accomplish different tasks, i.e., cellular work—either involved in mechanical motion, transport, or chemical changes. ATP phosphorylation is a ubiquitous solution to problems involved in cellular work, which is taking place in our cells constantly and generates a high demand for ATP in our cells. Luckily, our bodies are equipped with mechanisms for quickly and efficiently regenerating hydrolyzed ATP from by-products of catabolic processes (more on this later).

Metabolic (energetic) and catabolic (break down) pathways of cellular respiration, as a whole, represent a complex and tangled web of biochemical interactions. Given this complexity, biologists have seen fit to break this complexity into two basic processes comprising cellular respiration: (1) the citric acid cycle (a.k.a., the Krebs cycle) and (2) oxidative phosphorylation. Broadly speaking, this order represents a potentially but not necessarily in-line time series of events classically taught from the perspective of breaking down glucose molecules into energy in the form of ATP. Now, we take a closer look at each of these steps in cellular respiration.

Glycolysis, considered by many the first stage of cellular respiration although making this designation is committing a semantic error (cellular respiration only means processes using oxygen in CR), refers to biochemical processing our cells carry out in the cytosol, or liquid matrix comprising the extra-organellar (NS) space within cells, which serves the purpose of breaking individual glucose molecules (6-carbon ringed polysaccharide monomers) into two pyruvate molecules (3-carbon chemical compound). This evolves a small amount of ATP. Glycolysis is comprised of a ten-step process. In the early stages, the energy investment phase, cells burn two molecules of ATP; in the latter half of the whole series of reactions, two molecules of pyruvate (3-carbon molecule formed from breaking the 6-carbon glucose ring in two using Aldolase), four ATP molecules (net of two per glucose molecule) and two molecules of NADH are generated per starting glucose monomer. Pyruvate, after being shuttled into the mitochondrion, may be further oxidized through the citric acid cycle (CAC) and or by oxidative phosphorylation (OP) machinery, but this only can happen if oxygen is present in the cell. Alternatively, NADH, the reduced form of NAD+, holds electrons which can be used by CAC and OP processes to yield waaaayyy more energy than glycolysis per unit glucose starting material (as you'll see next post).

What I really want to harp on here is that this stuff is important! Really, really, really important, actually. Everyone should be interested in learning about this because biology is everyone's problem by virtue of our biological nature. Learning about biology is learning about your history, your form, your function, your relatives, your disease, your world. No biological entities could move or do any work without a means of converting energy in food to useable form in our cells, which are uniquely equipped with machinery to carry out highly specialized functions maintaining life as we know it. Next, I'll review another troubling set of ideas forming the remainder of cellular respiration: the citric acid cycle and oxidative phosphorylation.

Transformers

Went and saw Transformers with family and friends last week. My take: blown away. I am still just pumped by the overrunning excitement of that experience (late show: 9:30 – 12:00 midnight). Not only was it a real stepping stone to take some time and connect with my family through an entertainment experience like that (because it’s something we haven’t done together in a long time), but also there’s something in being able to watch dreams of your childhood come to life on the big screen, with a bunch of cinema magic in the mix. An added feature of seeing transformers was that I noticed in myself more maturity in my analysis of the world around me; in other words, it was fun to think about what I had just seen critically and to personalize the analysis by looking inward at what the experience meant to me. It was really great to see that my intellectual development is something that has branched out to other areas of life. So, what a deal!

Transformers was a great movie, not just a great movie-going experience. So, it would be fruitful to think about why this was the case. What made this movie so good? The science fiction aspect certainly has its benefits. Also, one cannot leave the Transformers experience and, after thoughtful analysis, conclude that this was a simple set of interactions going on, that it was the perfect film; rather, the movie proved more complex and multi-faceted with its own problems. I will consider both of these perspectives, the pros and cons, in more detail.

Again, in the best light, Transformers was really great. I think this has its foundations in an interesting story relating concepts involved in my imagination and play as a child, the action (graphics and sound) were incredible, the cars and techie stuff were cool and relevant to the times (new versions of fighter planes and beefy automobiles), comic relief was well-placed, and the movie’s underlying themes were provocative yet open to interpretation (thinking parents would get more out of this movie than good ole’ fashion good guys vs. bad guys, shoot-em-up, save the world stuff).

On the other hand, the film was not without its faults. After taking a reality check on the drive home from the theater, I realized this film had many difficulties. I will provide a few examples. First thing, the boy-girl story was unrealistic.

Megan Fox and Shai LaBoeuf (sp?) in Transformers.

Also, the alien robots (transformers and the other bots) took on distinctly human-influenced physical and emotional forms so as to be palatable to the human audience, which seems weird given this may be viewed as taking away from the “alien” nature of the story line. Another problem was that the audience was left without closure in some spaces; for example, some parts of the plot, which wove through several group’s stories (e.g., the computer hacker people and secretary of state), were dropped, never to be fully resolved in time and space on the screen (at one point in the movie, they just never show these characters again). In a skeptical context, certain claims in the story were never substantiated (e.g., the sector seven commando played by the guy from the Adam Sandler films used an unknown technology to knock out a small robot created from the black guy’s cell phone using power from “the cube,” but this was never explored or explained further by virtue of the timing of the Megatron invigoration). Furthermore, the whole autobot back story may be viewed as too short and or too shallow for the tastes of some moviegoers altogether. In other words, showing more of the whole cube’s story might have been fruitful. Also, what did it do in pre-war autobot society, why did it survive the transformer planet’s destruction, what was its power used for, etc.? Last but not least—and I could go on—the parent scenes and hottie girl’s “juvie record,” as in police record, stories could easily have been left out. Given these substantial lists of problems, one would be tempted to think the movie sank; however, the experience of the moviegoer, if like my own and potentially even acknowledging plainly each of these faults, tells a different story, a story of success, a story of entertainment and enjoyment. So, even though the problems could have fatally injured other films, for some reason this wasn’t the case with Transformers.

I conclude with reflection on the major themes of the movie. One cannot help but leave the cozy chairs, popcorn, and soda cups, not to mention THX surround system, of AMC theaters without having come away with two, maybe three essential themes of the film. I give several possibilities: (1) the failure of “I-know-more-than-you-do” and “rules-and-bureaucracy” leadership (i.e., big US government and national security, typical parenting issues) (2) the idea that the greatest achievement, the greatest good and virtue is sacrificing for a good cause—others, something bigger than yourself (e.g., the fate of the planet or the fate of the good guys, the autobots in this case), and (3) the idea that there is more to life than what you think, "more than meets the eye." I also thought it was cool how the autobots considered themselves living creatures, with humans representing more primitive species (don't get it, but interesting nonetheless).

Maybe, you'll hear more about this later...