The Bright Crystal

The crazy-complicated structure of the ribosome, solved by x-ray crystallography (Source
Drug development used to be accomplished by the chemical equivalent of what you might call the spaghetti method: Throw a bunch of molecules against the wall and see what sticks. More recently, pharmaceutical companies have applied a more rational approach, using the molecular structures of drug targets to design molecules that “fit” them like a lock to a key.
The technique most often used to solve those molecular structures is x-ray crystallography. With this approach, which turned 100 years old in November, a high-powered beam of x-rays is shot at a crystal of protein molecules. The x-rays collide with the crystal’s atoms, scattering at specific angles. Working backwards from that information, researchers can figure out the original structure.
Over at Boing Boing, Maggie Koerth-Baker recently came up with a really fantastic analogy to explain this idea. X-ray crystallography, she wrote, is

… a method of determining the shape and structure of things that we can’t see with our own eyes. Imagine that you have captured Wonder Woman’s invisible airplane. You can’t see it. But you know it’s there because when you throw a rubber ball at the space, the ball bounces back to you. If you could throw enough rubber balls, from all different sides, and measure their trajectory and speed as they bounced back, you could probably get a pretty good idea of the shape of the plane.

Anyhoo, as the name of the technique implies, the key to crystallography is, well, crystals. But not all proteins crystallize, and even with those that do, it can be hard to grow crystals large enough for the technique to work.
Recently, though, a pair of technology developments have made it possible (in some cases) to work around these problems.

The first development was the commissioning in the past few years of ultra-bright x-ray sources in California (the Linac Coherent Light Source at Stanford) and Japan. These so-called “x-ray free electron lasers” (X-FELs) shoot incredibly bright, incredibly short x-ray pulses, pulses that are so intense that they destroy a sample in a fraction of a second, but not before the x-rays (which travel at the speed of light, natch) have bounced off of it.

The reason crystals are required in crystallography is that any one diffraction event is hard to see. The regularly spaced molecules inside a crystal amplify that relatively weak signal, simplifying detection and structure determination. As it turns out, the brighter an x-ray source, the smaller the crystal required to obtain such data has to be, and with X-FELs, the crystals can be very small indeed – on the order of millionths of a meter (micrometers) in size, and perhaps even smaller.

Which brings me to the second development. In the March issue of the journal Nature Methods, a team of researchers led by Michael Duszenko in Germany showed that some proteins that cannot crystallize in a test tube will crystallize inside insect cells. Protein chemists often use cells as molecular factories to obtain large quantities of protein. But the goal is to extract the protein from the cells, not have them crystalize inside of them. Generally speaking, protein crystallization inside cells is a bad thing, the kind of thing researchers really don’t want to see; Duszenko and his team are the first to capitalize on this so-called “in vivo crystallization” phenomenon.

The crystals Duszenko’s team collected are quite small, of course –- they fit inside cells, after all — and in that initial study, they were on the order of 1 micrometer wide and 15 micrometers long. But as it turns out, they are big enough for the X-FEL. In the March paper, the team showed that these crystals will diffract x-rays in the X-FEL, but they didn’t solve the resulting structure.

Now, in a paper published Nov. 29 in Science, they have. They did it by combining X-FEL and in vivo crystallization to solve the structure of a trypsanosomal enzyme called cathepsin-B, a potential drug target for African sleeping sickness.

The team sprayed a stream of tiny enzyme crystals (each about 1 x 1 x 11 micrometers) into the path of the X-FEL, which fired discrete pulses of x-ray, each just 40 femtoseconds, or 0.000000000000040 seconds long, 120 times per second. Every so often, one of those pulses would collide with a crystal, and a nearby camera would capture the event.

Serial femtosecond crystallography (Source Continue reading

Double X Science panel at GeekGirlCon 2012

On Sunday, Aug 12, Managing Editor Emily Willingham, Chemistry Editor Adrienne Roehrich, and Contributor Raychelle Burks spoke on bringing science to you. Here’s a summary of our panel.

Photo by Ryan Roehrich and used with permission.

We started with a welcome and gratitude to the organizers and attendees and our tagline “Science, I am Just That Into You.” We were selected to appear with a lot of fantastic programming over the weekend.
We introduced our 3 panelists:
Adrienne Roehrich, your panel moderator and the chemistry editor at Double X Science
Emily Willingham, founder and managing editor 
Ray Burks, contributor to Double X Science 
Photo by Ryan Roehrich and used with permission.

All 3 have PhDs in their respective fields – Emily is a developmental biologist, Ray is an analytical chemist, and Adrienne is a physical chemist. Emily and Ray are prolific writers. You can find their articles all over the internet and in print. Ray is a staff member for GeekGirlCon and Adrienne is a Special Agent volunteer. All 3 are active on social media and welcome live-tweeting and suggest the #DXS hashtag along with the #GGC12. And you can use the @DoubleXSci for the panel.

Then a poll of the room to see who had heard of the site. Only a few attendees were already familiar with the site, so we told them that DoubleXScience covers a lot of current science. For example on (the previous) Monday, Emily posted about the Mars Curiosity Rover touchdown. In July, the physics editor covered the Higgs particle announcement. We also cover timeless, yet updated science, such as pregnancy and other health issues that we editors perceive to be of interest to ourselves and our readers.
It’s hard to discuss what Double X Science is without discussing who it is.
After a review of who all the people on that particular slide are and what they have to do with Double X Science, three questions were asked by the moderator:
In November of 2011, Emily founded Double X Science, Emily what was your motivation in founding the site and what was then and is now your vision for it?
As mentioned, we have content from editors, other sites and contributors. Ray was the first contributor to the site – what attracted you to Double X Science?
What do the attendees want to know?
And then our discussion really got started. Thankfully, we had 3 great tweeters attending, so I can just point you along their tweets:

[<a href=”″ target=”_blank”>View the story “Double X Science panel at GeekGirlCon 2012” on Storify</a>]

Photo by Adrienne Roehrich and used with permission.

Posted by Adrienne M. Roehrich, Chemistry Editor

A Once-in-a-Lifetime Truly Double X Event: Venus in Transit

By DXS Physics Editor Matthew Francis, who usually brings you Everyday Science. As you will see, this is science of the Not-So-Everyday sort.

Perhaps the most important question to ask in science is “how do we know?” While it’s appropriate to ask this every day, today it feels even more so, as we prepare to witness a very rare astronomical event. This time, it’s happening on June 5, 2012; when this event occurred during the 18th century, it allowed astronomers to make the first precision measurements of the size of our Solar System. Captain James Cook, best known for his exploration of the Pacific (for Europe, that is—the natives already knew what was there), took a set of scientific instruments aboard his ship to Tahiti; other teams of researchers took measurements at those locations.

The rare event they observed was the transit of Venus: when Venus travels directly between Earth and the Sun, blocking a tiny amount of light. Astronomers in different locations timed the crossing of Venus across the Sun’s disc, and by comparing their numbers, were able to determine the distance between Earth and the Sun. With that distance in hand, they were able to calibrate the size of the entire Solar System. The 1769 observation was an international scientific effort (to use modern language), and while the results weren’t as good as the astronomers of the day had hoped, they still agreed with modern measurements.

Today we use a variety of techniques to measure distances, including radar ranging (bouncing radio waves off planets and timing the round trip), so we don’t have to wait for Venus transits anymore—which is good, since they aren’t common! The last Venus transit was in 2004, but the previous one before that was in 1882, and the next one will be in 2117. I got up very early in the morning on June 8, 2004, joining some fellow astronomy enthusiasts at the Rutgers observatory, where we took the photo you see at the top of the post.

The seemingly odd intervals between transits are because Earth’s and Venus’ orbits around the Sun don’t lie in the same plane. If you draw Earth’s orbit as an ellipse on a sheet of cardboard, and Venus’ orbit on another sheet of cardboard, they need to overlap in a small X pattern, as shown in the picture. The only times Venus will transit is when both Earth and Venus are on the same side of the Sun, and only when they are in the region where the cardboard pieces overlap. The angle (3.5°) in the picture is correct, but I’ve exaggerated the size of the Sun and the sizes of the “transit zones”; in truth, even though the Sun is huge compared to Earth, it’s not that big on the sky. If you do the real calculation, you find that Venus transits happen roughly twice per century, and those two events are separated by 8 years. It’s a rare and wonderful event!

Viewing the Transit

If you want to view the Venus transit, the first thing you should do is see if it will be visible where you live. (Hopefully the weather will cooperate too! Such is the life of an astronomer.) In Richmond, Virginia (where I live), the transit begins around 6 PM. If you’re in the area, the Science Museum of Virginia is hosting a free viewing on the lawn; many other cities and towns have similar events.

A common sense warning: please don’t look directly at the Sun! However, you don’t need fancy equipment or a big observatory to witness the transit. Two weeks ago, I observed the solar eclipse using nothing but a microwave macaroni-and-cheese container. By piercing a hole in the bottom of the tub, I created a simple pinhole camera. A small and kind of fuzzy image of the eclipse appeared on a piece of paper, which I photographed. (Obviously you can do better if you have better equipment—I happened to be far from home during the eclipse and used what I had on hand.) A piece of cardboard covered in aluminum foil with a small hole works better, and you can project the image right onto the sidewalk, the side of a building, or another screen.

If you have a pair of binoculars that use glass lenses (since plastic will melt), point the larger lens toward the Sun and the smaller lens onto a flat surface. (Again, don’t look through the binoculars if you value your eyeballs!) If you have a telescope with a mirror or glass lenses, you can also project the image onto a flat surface, or create a sun funnel. There are a lot of ways to view the Sun if the ones I mention don’t appeal to you.

As a word of caution: the Venus transit won’t look as impressive as a solar eclipse, since Venus is a lot farther away than the Moon. It will appear to be a small round shadow on the Sun’s disc. The thrill (for me at least) lies in the knowledge: you are viewing a planet not much smaller than Earth as it crosses between us and our home star! If it isn’t enough these events are rare, think of how significant it is to catch a glimpse of the sheer size of our Solar System, in a way we don’t usually get to see. And always, always remember to ask the question: “how do we know?”

Further Reading

If you want to know more about transits and why they are still scientifically important today, try these links:

Happy Venus-watching!

Science, health, medical news freaking you out? Do the Double X Double-Take first

Handy short-form version.

Have you seen the headlines? Skip them
You’ve probably seen a lot of headlines lately about autism and various behaviors, ways of being, or “toxins” that, the headlines tell you, are “linked” to it. Maybe you’re considering having a child and are mentally tallying up the various risk factors you have as a parent. Perhaps you have a child with autism and are now looking back, loaded with guilt that you ate high-fructose corn syrup or were overweight or too old or too near a freeway or not something enough that led to your child’s autism. Maybe you’re an autistic adult who’s getting a little tired of reading in these stories about how you don’t exist or how using these “risk factors” might help the world reduce the number of people who are like you.

Here’s the bottom line: No one knows precisely what causes the extremely diverse developmental difference we call autism. Research from around the world suggests a strong genetic component [PDF]. What headlines in the United States call an “epidemic” is, in all likelihood, largely attributable to expanded diagnostic inclusion, better identification, and, ironically, greater awareness of autism. In countries that have been able to assess overall population prevalence, such as the UK, rates seem to have held steady at about 1% for decades, which is about the current levels now identified among 8-year-olds in the United States. 

What anyone needs when it comes to headlines honking about a “link” to a specific condition is a mental checklist of what the article–and whatever research underlies it–is really saying. Previously, we brought you Real vs Fake Science: How to tell them apart. Now we bring you our Double X Double-Take checklist. Use it when you read any story about scientific research and human health, medicine, biology, or genetics.

The Double X Double-Take: What to do when reading science in the news
1. Skip the headline. Headlines are often misleading, at best, and can be wildly inaccurate. Forget about the headline. Pretend you never even saw the headline.

2. What is the basis of the article? Science news originates from several places. Often it’s a scientific paper. These papers come in several varieties. The ones that report a real study–lots of people or mice or flies, lots of data, lots of analysis, a hypothesis tested, statistics done–is considered “original research.” Those papers are the only ones that are genuinely original scientific studies. Words to watch for–terms that suggest no original research at all–are “review,” “editorial,” “perspective,” “commentary,” “case study” (these typically involve one or only a handful of cases, so no statistical analysis), and “meta-analysis.” None of these represents original findings from a scientific study. All but the last two are opinion. Also watch for “scientific meeting” and “conference.” That means that this information was presented without peer review at a scientific meeting. It hasn’t been vetted in any way.

3. Look at the words in the article. If what you’re reading contains words like “link,” “association,” “correlation,” or “risk,” then what the article is describing is a mathematical association between one thing (e.g., autism) and another (e.g., eating ice cream). It is likely not describing a biological connection between the two. In fact, popular articles seem to very rarely even cover scientific research that homes in on the biological connections. Why? Because these findings usually come in little bits and pieces that over time–often quite a bit of time–build into a larger picture showing a biological pathway by which Variable 1 leads to Outcome A. That’s not generally a process that’s particularly newsworthy, and the pathways can be both too specific and extremely confusing.

4. Look at the original source of the information. Google is your friend. Is the original source a scientific journal? At the very least, especially for original research, the abstract will be freely available. A news story based on a journal paper should provide a link to that abstract, but many, many news outlets do not do this–a huge disservice to the interested, engaged reader. At any rate, the article probably includes the name of a paper author and the journal of publication, and a quick Google search on both terms along with the subject (e.g., autism) will often find you the paper. If all you find is a news release about the paper–at outlets like ScienceDaily or PhysOrg–you are reading marketing materials. Period. And if there is no mention of publication in a journal, be very, very cautious in your interpretation of what’s being reported.

5. Remember that every single person involved in what you’re reading has a dog in the hunt. The news outlet wants clicks. For that reason, the reporter needs clicks. The researchers probably want attention to their research. The institutions where the researchers do their research want attention, prestige, and money. A Website may be trying to scare you into buying what they’re selling. Some people are not above using “sexy” science topics to achieve all of the above. Caveat lector

6. Ask a scientist. Twitter abounds with scientists and sciencey types who may be able to evaluate an article for you. I receive daily requests via email, Facebook, and Twitter for exactly that assistance, and I’m glad to provide it. Seriously, ask a scientist. You’ll find it hard to get us to shut up. We do science because we really, really like it. It sure ain’t for the money. [Edited to add: But see also an important caveat and an important suggestion from Maggie Koerth-Baker over at Boing Boing and, as David Bradley has noted over at ScienceBase, always remember #5 on this list when applying #6.] 


Case Study
Lately, everyone seems to be using “autism” as a way to draw eyeballs to their work. Below, I’m giving my own case study of exactly that phenomenon as an example of how to apply this checklist.

1. Headline: “Ten chemicals most likely to cause autism and learning disabilities” and “Could autism be caused by one of these 10 chemicals?” Double X Double-Take 1: Skip the headline. Check. Especially advisable as there is not one iota of information about “cause” involved here.

2. What is the basis of the articleEditorialConference. In other words, those 10 chemicals aren’t something researchers identified in careful studies as having a link to autism but instead are a list of suspects the editorial writers derived, a list that they’d developed two years ago at the mentioned conference. 

3. Look at the words in the articles. Suspected. Suggesting a link. In other words, what you’re reading below those headlines does not involve studies linking anything to autism. Instead, it’s based on an editorial listing 10 compounds [PDF] that the editorial authors suspect might have something to do with autism (NB: Both linked stories completely gloss over the fact that most experts attribute the rise in autism diagnoses to changing and expanded diagnostic criteria, a shift in diagnosis from other categories to autism, and greater recognition and awareness–i.e., not to genetic changes or environmental factors. The editorial does the same). The authors do not provide citations for studies that link each chemical cited to autism itself, and the editorial itself is not focused on autism, per se, but on “neurodevelopmental” derailments in general.

4. Look at the original source of information. The source of the articles is an editorial, as noted. But one of these articles also provides a link to an actual research paper. The paper doesn’t even address any of the “top 10” chemicals listed but instead is about cigarette smoking. News stories about this study describe it as linking smoking during pregnancy and autism. Yet the study abstract states that they did not identify a link, saying “We found a null association between maternal smoking and pregnancy in ASDs and the possibility of an association with a higher-functioning ASD subgroup was suggested.” In other words: No link between smoking and autism. But the headlines and how the articles are written would lead you to believe otherwise. 

5. Remember that every single person involved has a dog in this hunt. Read with a critical eye. Ask yourself, what are people saying vs what real support exists for their assertions? Who stands to gain and in what way from having this information publicized? Think about the current culture–does the article or the research drag in “hot” topics (autism, obesity, fats, high-fructose corn syrup, “toxins,” Kim Kardashian) without any real basis for doing so? 

6. Ask a scientist. Why, yes, I am a scientist, so I’ll respond. My field of research for 10 years happens to have been endocrine-disrupting compounds. I’ve seen literally one drop of a compound dissolved in a trillion drops of solvent shift development of a turtle from male to female. I’ve seen the negative embryonic effects of pesticides and an over-the-counter antihistamine on penile development in mice. I know well the literature that runs to the thousands of pages indicating that we’ve got a lot of chemicals around us and in us that can have profound influences during sensitive periods of development, depending on timing, dose, species, and what other compounds may be involved. Endocrine disruptors or “toxins” are a complex group with complex interactions and effects and can’t be treated as a monolith any more than autism should be.

What I also know is that synthetic endocrine-disruptors have been around for more than a century and that natural ones for far, far longer. Do I think that the “top 10” chemicals require closer investigation and regulation? Yes. But not because I think they’re causative in some autism “epidemic.” We’ve got sufficiently compelling evidence of their harm already without trying to use “autism” as a marketing tool to draw attention to them. Just as a couple of examples: If coal-burning pollution (i.e., mercury) were causative in autism, I’d expect some evidence of high rates in, say, Victorian London, where the average household burned 11 tons of coal a year. If modern lead exposures were causative, I’d be expecting records from notoriously lead-burdened ancient Rome containing descriptions of the autism epidemic that surely took it over. 

Bottom line: We’ve got plenty of reasons for concern about the developmental effects of the compounds on this list. But we’ve got very limited reasons to make autism a focal point for testing them. Using the Double X Double-Take checklist helps demonstrate that.

By Emily Willingham, DXS managing editor 

Geektastic gift-giving ideas from Double X Science!

Shirt available via Zazzle

With the holidays fast approaching, the Double X Science team has come up with a great list of science-themed gifts to help you in your quest for the perfect present.  Not only are these gifts thoughtful, they are full of thought.  So go forth and spread some nerd love this year!




DVDs and Music


  • Hometown Puzzle, National Geographic, $39.95 Forget those generic puzzles found on the shelves of cookie-cutter toy stores, this highly personalized jigsaw will tickle the fancy of puzzle-lovers anywhere.  I’m probably going to get this for my mom.  NOTE: You need to order this by 12/13 if you want it by 12/25.




Other links

We are not the only blog containing geektastic gift suggestions. You can find some other great geeky gift-giving ideas here:

Compiled by Double X Science Editor and MotherGeek Jeanne Garbarino

Meet Double X Science

Welcome to Double X Science. This site exists to bring science to the woman in you, whoever she is, whatever she does. It’s not only for women in science, but also for women into science. If you’re single, married, dating, a mother, an aunt, a niece, a daughter, a sister, transgendered, born XX, or just feeling womanly…I hope that this site has something of science interest for you.

If you have suggestions for links, ideas, or stories for the site, please let me know.

Recommended reading about the importance of women in science and women into science

If you have suggestions for links, ideas, or stories for the site, drop me a line.

  • Watch on Mondays for the highlighted blog of the week.
  • Tuesdays will bring a science education tidbit, tip, or insight.
  • Wednesdays are type free but image rich.
  • Thursdays will surprise you with posts that make you think.
  • Fridays will bring you a news round-up of the science for the woman in you.

Literal XX Xplainer: How we can live with two X chromosomes

This cat also haz those two chromosomes 
to blame for that splotch on its face.
By Emily Willingham, DXS managing editor

We are “Double X Science” because we target evidence-based information to women, most of whom carry two X chromosomes, although exceptions exist. Some women carry a single X chromosome, and some people can be XY and develop and/or identify as female. That’s one reason we mention “the woman in you” here at Double X Science.

But today, I’m writing about those of us who have at least two X chromosomes. You may know that usually, carrying around a complete extra chromosome can lead to developmental differences, health problems, or even fetal or infant death. How is it that women can walk around with two X chromosomes in each body cell–and the X is a huge chromosome–yet men get by just fine with only one? What are we dealing with here: a half a dose of X (for men) or a double dose of X (for women)?

X chromosome
The answer? Women are typically the ones engaging in what’s known as “dosage compensation.” To manage our double dose of X, each of our cells shuts down one of the two X chromosomes it carries. The result is that we express the genes on only one of our X chromosomes in a given cell. This random expression of one X chromosome in each cell makes each woman a lovely mosaic of genetic expression (although not true genetic mosaicism), varying from cell to cell in whether we use genes from X chromosome 1 or from X chromosome 2.

Because these gene forms can differ between the two X chromosomes, we are simply less uniform in what our X chromosome genes do than are men. An exception is men who are XXY, who also shut down one of those X chromosomes in each body cell; women who are XXX shut down two X chromosomes in each cell. The body is deadly serious about this dosage compensation thing and will tolerate no Xtra dissent.

If we kept the entire X chromosome active, that would be a lot of Xtra gene dosage. The X chromosome contains about 1100 genes, and in humans, about 300 diseases and disorders are linked to genes on this chromosome, including hemophilia and Duchenne muscular dystrophy. Because males get only one chromosome, these X-linked diseases are more frequent among males–if the X chromosome they get has a gene form that confers disease, males have no backup X chromosome to make up for the deficit. Women do and far more rarely have X-linked diseases like hemophilia or X-linked differences like color blindness, although they may be subtly symptomatic depending on how frequently a “bad” version of the gene is silenced relative to the “good” version.

The most common example of the results of the random-ish gene silencing XX mammals do is the calico or tortoiseshell cat. You may have heard that if a cat’s calico, it’s female. That’s because the cat owes its splotchy coloring to having two X chromosome genes for coat color, which come in a couple of versions. One version of the gene results in brown coloring while the other produces orange. If a cat carries both forms, one on each X, wherever the cells shut down the brown X, the cat is orange. Wherever cells shut down the orange X, the cat is brown. The result? The cat can haz calico. 

Mary Lyon (Source)
Cells “shut down” the X by slathering it with a kind of chemical tag that makes its gene sequences inaccessible. This version of genetic Liquid Paper means that the cellular machinery responsible for using the gene sequences can’t detect them. The inactivated chromosome even has a special name: It’s called a Barr body. The XXer who developed a hypothesis to explain how XX/XY mammals compensate for gene dosage is Mary Lyon, and the process of silencing an X by condensing it is fittingly called lyonization. Her hypothesis, based on observations of coat color in mice, became a law–the Lyon Law–in 2011.

Barr bodies (arrows).
Yet the silencing of that single chromosome in each XX cell isn’t total. As it turns out, women don’t shut down the second X chromosome entirely. The molecular Liquid Paper leaves clusters of sequences available, as many as 300 genes in some women. That means that women are walking around with full double doses of some X chromosome genes. In addition, no two women silence or express precisely the same sequences on the “silenced” X chromosome. 

What’s equally fascinating is that many of the genes that go unsilenced on a Barr body are very like some genes on the Y chromosome, and the X and Y chromosomes share a common chromosomal ancestor. Thus, the availability of these genes on an otherwise silenced X chromosome may ensure that men and women have the same Y chromosome-related gene dosage, with men getting theirs from an X and a Y and women from having two X chromosomes with Y-like genes.  

Not all genes expressed on the (mostly) silenced X are Y chromosome cross-dressers, however. The fact is, women are more complex than men, genomically speaking. Every individual woman may express a suite of X-related genes that differs from that of the woman next to her and that differs even more from that of the man across the room. Just one more thing to add to that sense of mystery and complexity that makes us so very, very double X-ey.

[ETA: Some phrases in this post may have appeared previously in similar form in Biology Digest, but copyright for all material belongs to EJW.]

Biology Explainer: The big 4 building blocks of life–carbohydrates, fats, proteins, and nucleic acids

The short version
  • The four basic categories of molecules for building life are carbohydrates, lipids, proteins, and nucleic acids.
  • Carbohydrates serve many purposes, from energy to structure to chemical communication, as monomers or polymers.
  • Lipids, which are hydrophobic, also have different purposes, including energy storage, structure, and signaling.
  • Proteins, made of amino acids in up to four structural levels, are involved in just about every process of life.                                                                                                      
  • The nucleic acids DNA and RNA consist of four nucleotide building blocks, and each has different purposes.
The longer version
Life is so diverse and unwieldy, it may surprise you to learn that we can break it down into four basic categories of molecules. Possibly even more implausible is the fact that two of these categories of large molecules themselves break down into a surprisingly small number of building blocks. The proteins that make up all of the living things on this planet and ensure their appropriate structure and smooth function consist of only 20 different kinds of building blocks. Nucleic acids, specifically DNA, are even more basic: only four different kinds of molecules provide the materials to build the countless different genetic codes that translate into all the different walking, swimming, crawling, oozing, and/or photosynthesizing organisms that populate the third rock from the Sun.


Big Molecules with Small Building Blocks

The functional groups, assembled into building blocks on backbones of carbon atoms, can be bonded together to yield large molecules that we classify into four basic categories. These molecules, in many different permutations, are the basis for the diversity that we see among living things. They can consist of thousands of atoms, but only a handful of different kinds of atoms form them. It’s like building apartment buildings using a small selection of different materials: bricks, mortar, iron, glass, and wood. Arranged in different ways, these few materials can yield a huge variety of structures.

We encountered functional groups and the SPHONC in Chapter 3. These components form the four categories of molecules of life. These Big Four biological molecules are carbohydrates, lipids, proteins, and nucleic acids. They can have many roles, from giving an organism structure to being involved in one of the millions of processes of living. Let’s meet each category individually and discover the basic roles of each in the structure and function of life.

You have met carbohydrates before, whether you know it or not. We refer to them casually as “sugars,” molecules made of carbon, hydrogen, and oxygen. A sugar molecule has a carbon backbone, usually five or six carbons in the ones we’ll discuss here, but it can be as few as three. Sugar molecules can link together in pairs or in chains or branching “trees,” either for structure or energy storage.

When you look on a nutrition label, you’ll see reference to “sugars.” That term includes carbohydrates that provide energy, which we get from breaking the chemical bonds in a sugar called glucose. The “sugars” on a nutrition label also include those that give structure to a plant, which we call fiber. Both are important nutrients for people.

Sugars serve many purposes. They give crunch to the cell walls of a plant or the exoskeleton of a beetle and chemical energy to the marathon runner. When attached to other molecules, like proteins or fats, they aid in communication between cells. But before we get any further into their uses, let’s talk structure.

The sugars we encounter most in basic biology have their five or six carbons linked together in a ring. There’s no need to dive deep into organic chemistry, but there are a couple of essential things to know to interpret the standard representations of these molecules.

Check out the sugars depicted in the figure. The top-left molecule, glucose, has six carbons, which have been numbered. The sugar to its right is the same glucose, with all but one “C” removed. The other five carbons are still there but are inferred using the conventions of organic chemistry: Anywhere there is a corner, there’s a carbon unless otherwise indicated. It might be a good exercise for you to add in a “C” over each corner so that you gain a good understanding of this convention. You should end up adding in five carbon symbols; the sixth is already given because that is conventionally included when it occurs outside of the ring.

On the left is a glucose with all of its carbons indicated. They’re also numbered, which is important to understand now for information that comes later. On the right is the same molecule, glucose, without the carbons indicated (except for the sixth one). Wherever there is a corner, there is a carbon, unless otherwise indicated (as with the oxygen). On the bottom left is ribose, the sugar found in RNA. The sugar on the bottom right is deoxyribose. Note that at carbon 2 (*), the ribose and deoxyribose differ by a single oxygen.

The lower left sugar in the figure is a ribose. In this depiction, the carbons, except the one outside of the ring, have not been drawn in, and they are not numbered. This is the standard way sugars are presented in texts. Can you tell how many carbons there are in this sugar? Count the corners and don’t forget the one that’s already indicated!

If you said “five,” you are right. Ribose is a pentose (pent = five) and happens to be the sugar present in ribonucleic acid, or RNA. Think to yourself what the sugar might be in deoxyribonucleic acid, or DNA. If you thought, deoxyribose, you’d be right.

The fourth sugar given in the figure is a deoxyribose. In organic chemistry, it’s not enough to know that corners indicate carbons. Each carbon also has a specific number, which becomes important in discussions of nucleic acids. Luckily, we get to keep our carbon counting pretty simple in basic biology. To count carbons, you start with the carbon to the right of the non-carbon corner of the molecule. The deoxyribose or ribose always looks to me like a little cupcake with a cherry on top. The “cherry” is an oxygen. To the right of that oxygen, we start counting carbons, so that corner to the right of the “cherry” is the first carbon. Now, keep counting. Here’s a little test: What is hanging down from carbon 2 of the deoxyribose?

If you said a hydrogen (H), you are right! Now, compare the deoxyribose to the ribose. Do you see the difference in what hangs off of the carbon 2 of each sugar? You’ll see that the carbon 2 of ribose has an –OH, rather than an H. The reason the deoxyribose is called that is because the O on the second carbon of the ribose has been removed, leaving a “deoxyed” ribose. This tiny distinction between the sugars used in DNA and RNA is significant enough in biology that we use it to distinguish the two nucleic acids.

In fact, these subtle differences in sugars mean big differences for many biological molecules. Below, you’ll find a couple of ways that apparently small changes in a sugar molecule can mean big changes in what it does. These little changes make the difference between a delicious sugar cookie and the crunchy exoskeleton of a dung beetle.

Sugar and Fuel

A marathon runner keeps fuel on hand in the form of “carbs,” or sugars. These fuels provide the marathoner’s straining body with the energy it needs to keep the muscles pumping. When we take in sugar like this, it often comes in the form of glucose molecules attached together in a polymer called starch. We are especially equipped to start breaking off individual glucose molecules the minute we start chewing on a starch.

Double X Extra: A monomer is a building block (mono = one) and a polymer is a chain of monomers. With a few dozen monomers or building blocks, we get millions of different polymers. That may sound nutty until you think of the infinity of values that can be built using only the numbers 0 through 9 as building blocks or the intricate programming that is done using only a binary code of zeros and ones in different combinations.

Our bodies then can rapidly take the single molecules, or monomers, into cells and crack open the chemical bonds to transform the energy for use. The bonds of a sugar are packed with chemical energy that we capture to build a different kind of energy-containing molecule that our muscles access easily. Most species rely on this process of capturing energy from sugars and transforming it for specific purposes.

Polysaccharides: Fuel and Form

Plants use the Sun’s energy to make their own glucose, and starch is actually a plant’s way of storing up that sugar. Potatoes, for example, are quite good at packing away tons of glucose molecules and are known to dieticians as a “starchy” vegetable. The glucose molecules in starch are packed fairly closely together. A string of sugar molecules bonded together through dehydration synthesis, as they are in starch, is a polymer called a polysaccharide (poly = many; saccharide = sugar). When the monomers of the polysaccharide are released, as when our bodies break them up, the reaction that releases them is called hydrolysis.

Double X Extra: The specific reaction that hooks one monomer to another in a covalent bond is called dehydration synthesis because in making the bond–synthesizing the larger molecule–a molecule of water is removed (dehydration). The reverse is hydrolysis (hydro = water; lysis = breaking), which breaks the covalent bond by the addition of a molecule of water.

Although plants make their own glucose and animals acquire it by eating the plants, animals can also package away the glucose they eat for later use. Animals, including humans, store glucose in a polysaccharide called glycogen, which is more branched than starch. In us, we build this energy reserve primarily in the liver and access it when our glucose levels drop.

Whether starch or glycogen, the glucose molecules that are stored are bonded together so that all of the molecules are oriented the same way. If you view the sixth carbon of the glucose to be a “carbon flag,” you’ll see in the figure that all of the glucose molecules in starch are oriented with their carbon flags on the upper left.

The orientation of monomers of glucose in polysaccharides can make a big difference in the use of the polymer. The glucoses in the molecule on the top are all oriented “up” and form starch. The glucoses in the molecule on the bottom alternate orientation to form cellulose, which is quite different in its function from starch.

Storing up sugars for fuel and using them as fuel isn’t the end of the uses of sugar. In fact, sugars serve as structural molecules in a huge variety of organisms, including fungi, bacteria, plants, and insects.

The primary structural role of a sugar is as a component of the cell wall, giving the organism support against gravity. In plants, the familiar old glucose molecule serves as one building block of the plant cell wall, but with a catch: The molecules are oriented in an alternating up-down fashion. The resulting structural sugar is called cellulose.

That simple difference in orientation means the difference between a polysaccharide as fuel for us and a polysaccharide as structure. Insects take it step further with the polysaccharide that makes up their exoskeleton, or outer shell. Once again, the building block is glucose, arranged as it is in cellulose, in an alternating conformation. But in insects, each glucose has a little extra added on, a chemical group called an N-acetyl group. This addition of a single functional group alters the use of cellulose and turns it into a structural molecule that gives bugs that special crunchy sound when you accidentally…ahem…step on them.

These variations on the simple theme of a basic carbon-ring-as-building-block occur again and again in biological systems. In addition to serving roles in structure and as fuel, sugars also play a role in function. The attachment of subtly different sugar molecules to a protein or a lipid is one way cells communicate chemically with one another in refined, regulated interactions. It’s as though the cells talk with each other using a specialized, sugar-based vocabulary. Typically, cells display these sugary messages to the outside world, making them available to other cells that can recognize the molecular language.

Lipids: The Fatty Trifecta

Starch makes for good, accessible fuel, something that we immediately attack chemically and break up for quick energy. But fats are energy that we are supposed to bank away for a good long time and break out in times of deprivation. Like sugars, fats serve several purposes, including as a dense source of energy and as a universal structural component of cell membranes everywhere.

Fats: the Good, the Bad, the Neutral

Turn again to a nutrition label, and you’ll see a few references to fats, also known as lipids. (Fats are slightly less confusing that sugars in that they have only two names.) The label may break down fats into categories, including trans fats, saturated fats, unsaturated fats, and cholesterol. You may have learned that trans fats are “bad” and that there is good cholesterol and bad cholesterol, but what does it all mean?

Let’s start with what we mean when we say saturated fat. The question is, saturated with what? There is a specific kind of dietary fat call the triglyceride. As its name implies, it has a structural motif in which something is repeated three times. That something is a chain of carbons and hydrogens, hanging off in triplicate from a head made of glycerol, as the figure shows.  Those three carbon-hydrogen chains, or fatty acids, are the “tri” in a triglyceride. Chains like this can be many carbons long.

Double X Extra: We call a fatty acid a fatty acid because it’s got a carboxylic acid attached to a fatty tail. A triglyceride consists of three of these fatty acids attached to a molecule called glycerol. Our dietary fat primarily consists of these triglycerides.

Triglycerides come in several forms. You may recall that carbon can form several different kinds of bonds, including single bonds, as with hydrogen, and double bonds, as with itself. A chain of carbon and hydrogens can have every single available carbon bond taken by a hydrogen in single covalent bond. This scenario of hydrogen saturation yields a saturated fat. The fat is saturated to its fullest with every covalent bond taken by hydrogens single bonded to the carbons.

Saturated fats have predictable characteristics. They lie flat easily and stick to each other, meaning that at room temperature, they form a dense solid. You will realize this if you find a little bit of fat on you to pinch. Does it feel pretty solid? That’s because animal fat is saturated fat. The fat on a steak is also solid at room temperature, and in fact, it takes a pretty high heat to loosen it up enough to become liquid. Animals are not the only organisms that produce saturated fat–avocados and coconuts also are known for their saturated fat content.

The top graphic above depicts a triglyceride with the glycerol, acid, and three hydrocarbon tails. The tails of this saturated fat, with every possible hydrogen space occupied, lie comparatively flat on one another, and this kind of fat is solid at room temperature. The fat on the bottom, however, is unsaturated, with bends or kinks wherever two carbons have double bonded, booting a couple of hydrogens and making this fat unsaturated, or lacking some hydrogens. Because of the space between the bumps, this fat is probably not solid at room temperature, but liquid.

You can probably now guess what an unsaturated fat is–one that has one or more hydrogens missing. Instead of single bonding with hydrogens at every available space, two or more carbons in an unsaturated fat chain will form a double bond with carbon, leaving no space for a hydrogen. Because some carbons in the chain share two pairs of electrons, they physically draw closer to one another than they do in a single bond. This tighter bonding result in a “kink” in the fatty acid chain.

In a fat with these kinks, the three fatty acids don’t lie as densely packed with each other as they do in a saturated fat. The kinks leave spaces between them. Thus, unsaturated fats are less dense than saturated fats and often will be liquid at room temperature. A good example of a liquid unsaturated fat at room temperature is canola oil.

A few decades ago, food scientists discovered that unsaturated fats could be resaturated or hydrogenated to behave more like saturated fats and have a longer shelf life. The process of hydrogenation–adding in hydrogens–yields trans fat. This kind of processed fat is now frowned upon and is being removed from many foods because of its associations with adverse health effects. If you check a food label and it lists among the ingredients “partially hydrogenated” oils, that can mean that the food contains trans fat.

Double X Extra: A triglyceride can have up to three different fatty acids attached to it. Canola oil, for example, consists primarily of oleic acid, linoleic acid, and linolenic acid, all of which are unsaturated fatty acids with 18 carbons in their chains.

Why do we take in fat anyway? Fat is a necessary nutrient for everything from our nervous systems to our circulatory health. It also, under appropriate conditions, is an excellent way to store up densely packaged energy for the times when stores are running low. We really can’t live very well without it.

Phospholipids: An Abundant Fat

You may have heard that oil and water don’t mix, and indeed, it is something you can observe for yourself. Drop a pat of butter–pure saturated fat–into a bowl of water and watch it just sit there. Even if you try mixing it with a spoon, it will just sit there. Now, drop a spoon of salt into the water and stir it a bit. The salt seems to vanish. You’ve just illustrated the difference between a water-fearing (hydrophobic) and a water-loving (hydrophilic) substance.

Generally speaking, compounds that have an unequal sharing of electrons (like ions or anything with a covalent bond between oxygen and hydrogen or nitrogen and hydrogen) will be hydrophilic. The reason is that a charge or an unequal electron sharing gives the molecule polarity that allows it to interact with water through hydrogen bonds. A fat, however, consists largely of hydrogen and carbon in those long chains. Carbon and hydrogen have roughly equivalent electronegativities, and their electron-sharing relationship is relatively nonpolar. Fat, lacking in polarity, doesn’t interact with water. As the butter demonstrated, it just sits there.

There is one exception to that little maxim about fat and water, and that exception is the phospholipid. This lipid has a special structure that makes it just right for the job it does: forming the membranes of cells. A phospholipid consists of a polar phosphate head–P and O don’t share equally–and a couple of nonpolar hydrocarbon tails, as the figure shows. If you look at the figure, you’ll see that one of the two tails has a little kick in it, thanks to a double bond between the two carbons there.

Phospholipids form a double layer and are the major structural components of cell membranes. Their bend, or kick, in one of the hydrocarbon tails helps ensure fluidity of the cell membrane. The molecules are bipolar, with hydrophilic heads for interacting with the internal and external watery environments of the cell and hydrophobic tails that help cell membranes behave as general security guards.

The kick and the bipolar (hydrophobic and hydrophilic) nature of the phospholipid make it the perfect molecule for building a cell membrane. A cell needs a watery outside to survive. It also needs a watery inside to survive. Thus, it must face the inside and outside worlds with something that interacts well with water. But it also must protect itself against unwanted intruders, providing a barrier that keeps unwanted things out and keeps necessary molecules in.

Phospholipids achieve it all. They assemble into a double layer around a cell but orient to allow interaction with the watery external and internal environments. On the layer facing the inside of the cell, the phospholipids orient their polar, hydrophilic heads to the watery inner environment and their tails away from it. On the layer to the outside of the cell, they do the same.
As the figure shows, the result is a double layer of phospholipids with each layer facing a polar, hydrophilic head to the watery environments. The tails of each layer face one another. They form a hydrophobic, fatty moat around a cell that serves as a general gatekeeper, much in the way that your skin does for you. Charged particles cannot simply slip across this fatty moat because they can’t interact with it. And to keep the fat fluid, one tail of each phospholipid has that little kick, giving the cell membrane a fluid, liquidy flow and keeping it from being solid and unforgiving at temperatures in which cells thrive.

Steroids: Here to Pump You Up?

Our final molecule in the lipid fatty trifecta is cholesterol. As you may have heard, there are a few different kinds of cholesterol, some of which we consider to be “good” and some of which is “bad.” The good cholesterol, high-density lipoprotein, or HDL, in part helps us out because it removes the bad cholesterol, low-density lipoprotein or LDL, from our blood. The presence of LDL is associated with inflammation of the lining of the blood vessels, which can lead to a variety of health problems.

But cholesterol has some other reasons for existing. One of its roles is in the maintenance of cell membrane fluidity. Cholesterol is inserted throughout the lipid bilayer and serves as a block to the fatty tails that might otherwise stick together and become a bit too solid.

Cholesterol’s other starring role as a lipid is as the starting molecule for a class of hormones we called steroids or steroid hormones. With a few snips here and additions there, cholesterol can be changed into the steroid hormones progesterone, testosterone, or estrogen. These molecules look quite similar, but they play very different roles in organisms. Testosterone, for example, generally masculinizes vertebrates (animals with backbones), while progesterone and estrogen play a role in regulating the ovulatory cycle.

Double X Extra: A hormone is a blood-borne signaling molecule. It can be lipid based, like testosterone, or short protein, like insulin.


As you progress through learning biology, one thing will become more and more clear: Most cells function primarily as protein factories. It may surprise you to learn that proteins, which we often talk about in terms of food intake, are the fundamental molecule of many of life’s processes. Enzymes, for example, form a single broad category of proteins, but there are millions of them, each one governing a small step in the molecular pathways that are required for living.

Levels of Structure

Amino acids are the building blocks of proteins. A few amino acids strung together is called a peptide, while many many peptides linked together form a polypeptide. When many amino acids strung together interact with each other to form a properly folded molecule, we call that molecule a protein.

For a string of amino acids to ultimately fold up into an active protein, they must first be assembled in the correct order. The code for their assembly lies in the DNA, but once that code has been read and the amino acid chain built, we call that simple, unfolded chain the primary structure of the protein.

This chain can consist of hundreds of amino acids that interact all along the sequence. Some amino acids are hydrophobic and some are hydrophilic. In this context, like interacts best with like, so the hydrophobic amino acids will interact with one another, and the hydrophilic amino acids will interact together. As these contacts occur along the string of molecules, different conformations will arise in different parts of the chain. We call these different conformations along the amino acid chain the protein’s secondary structure.

Once those interactions have occurred, the protein can fold into its final, or tertiary structure and be ready to serve as an active participant in cellular processes. To achieve the tertiary structure, the amino acid chain’s secondary interactions must usually be ongoing, and the pH, temperature, and salt balance must be just right to facilitate the folding. This tertiary folding takes place through interactions of the secondary structures along the different parts of the amino acid chain.

The final product is a properly folded protein. If we could see it with the naked eye, it might look a lot like a wadded up string of pearls, but that “wadded up” look is misleading. Protein folding is a carefully regulated process that is determined at its core by the amino acids in the chain: their hydrophobicity and hydrophilicity and how they interact together.

In many instances, however, a complete protein consists of more than one amino acid chain, and the complete protein has two or more interacting strings of amino acids. A good example is hemoglobin in red blood cells. Its job is to grab oxygen and deliver it to the body’s tissues. A complete hemoglobin protein consists of four separate amino acid chains all properly folded into their tertiary structures and interacting as a single unit. In cases like this involving two or more interacting amino acid chains, we say that the final protein has a quaternary structure. Some proteins can consist of as many as a dozen interacting chains, behaving as a single protein unit.

A Plethora of Purposes

What does a protein do? Let us count the ways. Really, that’s almost impossible because proteins do just about everything. Some of them tag things. Some of them destroy things. Some of them protect. Some mark cells as “self.” Some serve as structural materials, while others are highways or motors. They aid in communication, they operate as signaling molecules, they transfer molecules and cut them up, they interact with each other in complex, interrelated pathways to build things up and break things down. They regulate genes and package DNA, and they regulate and package each other.

As described above, proteins are the final folded arrangement of a string of amino acids. One way we obtain these building blocks for the millions of proteins our bodies make is through our diet. You may hear about foods that are high in protein or people eating high-protein diets to build muscle. When we take in those proteins, we can break them apart and use the amino acids that make them up to build proteins of our own.

Nucleic Acids

How does a cell know which proteins to make? It has a code for building them, one that is especially guarded in a cellular vault in our cells called the nucleus. This code is deoxyribonucleic acid, or DNA. The cell makes a copy of this code and send it out to specialized structures that read it and build proteins based on what they read. As with any code, a typo–a mutation–can result in a message that doesn’t make as much sense. When the code gets changed, sometimes, the protein that the cell builds using that code will be changed, too.

Biohazard!The names associated with nucleic acids can be confusing because they all start with nucle-. It may seem obvious or easy now, but a brain freeze on a test could mix you up. You need to fix in your mind that the shorter term (10 letters, four syllables), nucleotide, refers to the smaller molecule, the three-part building block. The longer term (12 characters, including the space, and five syllables), nucleic acid, which is inherent in the names DNA and RNA, designates the big, long molecule.

DNA vs. RNA: A Matter of Structure

DNA and its nucleic acid cousin, ribonucleic acid, or RNA, are both made of the same kinds of building blocks. These building blocks are called nucleotides. Each nucleotide consists of three parts: a sugar (ribose for RNA and deoxyribose for DNA), a phosphate, and a nitrogenous base. In DNA, every nucleotide has identical sugars and phosphates, and in RNA, the sugar and phosphate are also the same for every nucleotide.

So what’s different? The nitrogenous bases. DNA has a set of four to use as its coding alphabet. These are the purines, adenine and guanine, and the pyrimidines, thymine and cytosine. The nucleotides are abbreviated by their initial letters as A, G, T, and C. From variations in the arrangement and number of these four molecules, all of the diversity of life arises. Just four different types of the nucleotide building blocks, and we have you, bacteria, wombats, and blue whales.

RNA is also basic at its core, consisting of only four different nucleotides. In fact, it uses three of the same nitrogenous bases as DNA–A, G, and C–but it substitutes a base called uracil (U) where DNA uses thymine. Uracil is a pyrimidine.

DNA vs. RNA: Function Wars

An interesting thing about the nitrogenous bases of the nucleotides is that they pair with each other, using hydrogen bonds, in a predictable way. An adenine will almost always bond with a thymine in DNA or a uracil in RNA, and cytosine and guanine will almost always bond with each other. This pairing capacity allows the cell to use a sequence of DNA and build either a new DNA sequence, using the old one as a template, or build an RNA sequence to make a copy of the DNA.

These two different uses of A-T/U and C-G base pairing serve two different purposes. DNA is copied into DNA usually when a cell is preparing to divide and needs two complete sets of DNA for the new cells. DNA is copied into RNA when the cell needs to send the code out of the vault so proteins can be built. The DNA stays safely where it belongs.

RNA is really a nucleic acid jack-of-all-trades. It not only serves as the copy of the DNA but also is the main component of the two types of cellular workers that read that copy and build proteins from it. At one point in this process, the three types of RNA come together in protein assembly to make sure the job is done right.

 By Emily Willingham, DXS managing editor 
This material originally appeared in similar form in Emily Willingham’s Complete Idiot’s Guide to College Biology