"Make straight the path..."

I find cyclical processes hard to understand. Maybe it's because I grew up in the age of digital clocks.

When I see a cycle, I like to draw it out as a linear sequence. For example, here is Figure 17.18, linearized to show the steps involved in adding one amino acid to a polypeptide chain. Comparing the top and bottom cartoons, you can see that the end is the same as the beginning. But shown this way, it is easier for me to think of a "beginning" and an "end." Click to enlarge...

By the way, happy new Year!

Speaking of microcosms...

... everybody has a little trouble comprehending the relative sizes of things that are either very very big, or very very small. To better appreciate the relative sizes of very small things, you can zoom in here (thanks to the Genetics Department at the University of Utah).

Use the scroll bar at bottom to zoom. First you see the embryos of three different plants (coffee, rice, sesame). From this millimeter size range, you can zoom all the way down to a carbon atom (320 picometers in girth). Along the way, see a couple of biggish protozoans, a variety of human cells, and a single human chromosome; then you zoom past a baker's yeast and a bacterium. You see a mitochondrion, which is another sort of bacterium. The "coated vesicle" is what gets pinched in from the plasma membrane during endocytosis; it is about the same size as the HIV virus particle. The smallest virus shown, Rhinovirus, causes the common cold. It does not have a lipid envelope, but is just a package of RNA in a protein coat. It is about the same size as a ribosome.

Light Reactions of photosynthesis: new cleaned-up coloring page!

I finally found a few minutes to clean up (and slightly improve) my diagram of the "Light Reactions" of photosynthesis: now it is a proper coloring page, ready to print and color.
 Here it is (click to enlarge, ctrl-click or right-click to save...)

The improvement was to add, at bottom, an icon for the Calvin cycle (the "Dark Reactions"), showing how the Light Reactions supply the necessary ATP and NADPH. The Calvin cycle is, after all, the whole point. It's how plants get ALL their carbon. It's where all our food comes from! To build sugar out of carbon dioxide takes CHEMICAL ENERGY (ATP) and REDUCING POWER (NADPH).

Here is a colored version:

I know it looks bewildering at first, but it may be helpful. Questions? Ask!
Cheers,
Morgan G.

Speaking of time-lapse cinematography…

I highly recommend the movie "Microcosmos: the people of the grass."

This almost wordless 1996 flick shows us the lives of critters that are small enough to move around between blades of grass, as we might walk among the trees in a forest.

Further, the filmmakers show us events in the meadow-forest that happen too quickly or too slowly for human perception - respectively by slowing down or speeding up the playback of the film.

I thought of this as I was reading to my son from T.H. White's novel The Sword in the Stone: for the benefit of his pupil, the not-yet-King Arthur, Merlyn uses his magic to speed up time, so the young Arthur can evesdrop on the conversations of trees (he must listen at half a year per second, or 15 million-fold time compression), or on those of rocks (listening at two million years per second).

The makers of "Microcosmos" also use a remote-controlled helicopter, with a tiny high-resolution videocamera, to follow a dragonfly in its flight.

It's an utterly beautiful movie. If you've never seen it, or saw it only as a small child (it was released in 1996) you really should find yourself an uninterrupted 80 minutes to take it in. You can get it streamed on Netflix.

My idea of a good time: watching cells divide.

I'm not joking!
If you want to see what I mean, check out these truly beautiful time-lapse movies of cells changing shape, moving around, going through mitosis and proliferating - mostly in early embryos of various invertebrate animals such as insects, nematodes, echinoderms and ctenophores.

A time-lapse movie, if you don't know, is a movie made by taking a picture, waiting for a fixed amount of time, then taking another picture, and so on...

Just like any movie, really - but if you want to film cells dividing, you generally want to space the snapshots a few seconds apart, because it takes a few seconds for the scene to change perceptibly. That's just how slow the cytoskeleton moves, in most cells anyway. (It's important to keep the camera steady; if it's mounted on a microscope, make sure the table doesn't shake.)

You play the movie back at high speed, several frames per second, so you can see all of a fifteen-minute process in a few seconds.

Some of the movies in this gallery were made with a fluorescence microscope ("Live-label movies"). A specific molecule in the living cell is labeled with a fluorescent dye - actually a natural fluorescent protein - which absorbs high-energy (e.g., blue) light and emits lower-energy (e.g., green) light. With this method we can actually see how a particular kind of protein is distributed within the living cell. We just shine a strong blue light on the cells, and use a filter to let the green fluorescent through to the camera. If the cells contain a good deal of labeled tubulin, we can see green fluorescent microtubules growing, shrinking, and moving around - and during mitosis (or meiosis) the microtubule bundles of the spindle will be clearly visible.

Using genetic engineering methods, we can label any protein in this way. More about that later...

If you would like to know more about what you're seeing in any of these movies, feel free to ask me!

The Center for Cell Dynamics is unfortunately no longer operating at the UW's Friday Harbor Labs - it closed a couple years ago, due to a funding shortfall, and most of its members have gone to other places. It's nice that the website is still up.

Friday Harbor Labs itself is still going strong - if you ever want to spend a Spring or Summer term studying critters from the sea, it's one of the best places in the world to do that.

Starting out from Citrate: a poem about the Krebs cycle.

STARTING OUT FROM CITRATE

First, a rearrangement.
Then, Boom! Boom! Two explosions, each exhaling; each reduces NAD+.
In the second, CoA enters.

CoA is displaced by water; GTP is made.

Fumarate is made by reducing FAD.

Fumarate is thirsty, has a drink, and turns to Malate.

A final oxidation, NAD+ again reduced: Oxaloacetate!

Which then combines with acetate (CoA once again displaced by water):
Starting out from Citrate once again.

Errata

Oops: here are TWO mistakes that I found in earlier postings.

1. On Fermentation (10/25):
I wrote "… pyruvate oxidizes NAD+ to NADH, and is converted (reduced) to lactate ..."
In fact, pyruvate oxidizes NADH to NAD+.

2. In the Krebs cycle cartoon (10/28), ATP and ADP should respectively read GTP and GDP.

I've fixed these now, but I wanted to make sure nobody was misled.
cheers,
Morgan G.

Photosynthesis: Wow.

When I first started reading about photosynthesis, I was frightened, and felt sorry for myself, and for you too. But after cartooning up a comprehensive diagram, I feel much better. Photosynthesis is not so bad after all!

My cartoon diagram is a remodeled version of the textbook's Figure 10.12,  incorporating elements  of Figures 10.14 (cyclic e- flow from PSI) and 10.16 (spatial organization and proton pumping). Click to enlarge...

It might look messy to you, but for me it's easier to read than the textbook figures - maybe because I made it!

I would be interested to know: is there anyone who has tried this tactic of re-drawing textbook diagrams and found it NOT so helpful? It's humongously helpful to me; if you haven't tried it, I highly recommend you do.
Use a pencil, and keep it sharp; get a big eraser.

Meanwhile, you might enjoy printing out the above cartoon and adding colors to organize some of the information.
cheers,
Morgan G.

Krebs cycle - containing graphic content

Dear students,
Here is a cartoon of the Krebs cycle. Making and coloring it helped me learn the biochemistry!!

Compound names are abbreviated, which is fine, because you have memorized them already. (See previous post.)

The pie wedges making up the cycle are not equivalent in radius - that's because I drew them to show  number of carbon atoms in each compound. At the top, for example, acetyl coA donates a two-carbon fragment (the acetyl group) to four-carbon oxaloacetate, yielding six-carbon citrate. Two steps later, a CO2 molecule is split off, yielding a five-carbon molecule (alpha-ketoglutarate)...

The blue teardrop signs show where a water molecule enters a reaction (to be incorporated into organic molecules).

If you would like to color this yourself, here is a coloring page.  You can save the image and print out a few copies. (Please don't sell it without my permission.)

Students, when we meet next, let's have a quiz on the Krebs cycle!
cheers,
Morgan G.

Learning the Krebs Cycle: Step One

How in the world are you supposed to memorize the steps of the Krebs Cycle?

There are just eight steps, but many nearly all of these are reactions with two or more reactants and two or more products. It adds up fast.
For the exam, you are responsible for knowing six of the eight steps. Maybe you might as well just learn the whole thing.

I don't recall how I memorized the Krebs cycle, back in college.
As I try to learn it again, I am coming up with some tricks to break up the information into bite-size chunks, and spice them with tasty significance.



There are really two tasks here. We can do them one at a time.

The first task is to learn the names of the reactants, and where they go in the pathway.

The second task is to learn which of these reactions HARVEST ENERGY
(by reduction of NAD+ to NADH, or reduction of FAD to FADH2, or production of ATP) ...

…and/or RELEASE WASTE
(by splitting off a molecule of carbon dioxide).



The first task is relatively straightforward. Stare at the Krebs cycle diagram and utter the names of the metabolites, in order of appearance. Start with Citrate.

Citrate, Isocitrate, Alpha-Ketoglutarate, Succinyl-CoA, Succinate, Fumarate, Malate, Oxaloacetate.

Do it again, until these words are familiar to you.

Now make up a mnemonic to remind you of the order. I like to make up a sentence consisting of words that begin with the first letter (or better, the first two or three letters) of the corresponding word series.

Cities, isolated, actually suck successfully, fuming malodorous oxaloacetate.

You may be able to do better. (A dictionary helps.) Once you have a mnemonic you like, recite it till memorized. Then you can practice reciting the real thing.

I'll add a note on pronunciation. (You learn better if you can read out loud.)
Citrate, Iso-citrate, Alpha-Keto-glutarate, Succinyl-CoA, Succinate, Fumarate, Malate, Oxalo-acetate.


Later (posting this evening, I hope) I'll show you how I've tackled the second task. I've figured out a couple tricks for graphically conceptualizing the reaction cycle and remembering how and where you get energy harvest and waste production.

cheers,
Morgan G.

Fermentation: why?

Your teacher has advised you to open your textbook on the day before the lab and read pages 170-173. If you did this, you found a story about how cells can get energy from sugar when there is no oxygen around. It's called fermentation, and it is nicely summarized in Figure 9.17 of the textbook.

Recall that you can harvest a little bit of energy out of glycolysis: even before you send your pyruvate to be oxidized into carbon dioxide in the Krebs cycle, you've made a net profit of 2 ATP per glucose. Not much, but if there's no oxygen to accept electrons from NADH and FADH2, then the Krebs cycle stops, and glycolysis is the best you can do.

The real problem is that step 6 of glycolysis consumes NAD+. If you keep on doing glycolysis, you will quickly run out of NAD+ (it all gets reduced to NADH, which is useless without oxygen) and glycolysis will stop. How to turn that built-up NADH back into NAD+? Fermentation.

What you need is an oxidizing agent to take electrons away from NADH. Happily, the pyruvate that you get out of glycolysis can do this job. In the cells of animals such as ourselves, this happens directly: with the help of an enzyme, pyruvate oxidizes NADH to NAD+, and is converted (reduced) to lactate - which gets shipped out of the cell and detoxified by your liver.


Other critters, like yeast, take a short detour and first convert pyruvate to 2-acetaldehyde. This is used as an oxidizing agent to regenerate NAD+. In this reaction, 2-acetaldehyde is reduced to ethanol.


Regardless of how it's done, it's an elegant way to keep glycolysis going in the absence of oxygen. In one fell swoop, you do two essential jobs: regenerate NAD+ and funnel away pyruvate. Both of these jobs are important. Why? Because if the product of any reaction builds up to a high concentration, the reaction will slow down - and can even run backwards.

(Why is this so?)



The products of fermentation can be experienced directly: when you sprint up a long hill, your legs hurt as a result of lactic acid flooding out of the muscle cells. When you consume fruit that has been heavily colonized by yeast, ethanol enters your brain and your thinking becomes sloppy. If this happens, do not drive or operate machinery.

Here is another question: is all this writing helpful? If not, I won't do it.

Notetaking as creative process

More about taking notes:
It's about making the material your own.

When you write stuff down, you are creating a new model; though it's meant to mirror the piece of reality you're trying to grasp, it remains an original creation. It's a story written by you, for you. Tell the best story you can, in a language designed for you to understand.

Here's an example of how I take notes for myself. (Click to enlarge.)

I distill major points from the text. I draw lots of diagrams and cartoons. I copy (and often modify) figures from the text. Hand-copying things is a good way to remember them! Adding your own flavor and insight to this fresh copy makes the information still more memorable.
cheers,
Morgan G.

Slow down and read the textbook!

Welcome. This blog is dedicated to students taking AP/Honors Biology at ICS (LWSD), in the Fall term of 2011. I am a tutor to several students in this class. As I start writing, we are already some ways into the course: just past the second exam. The material is getting more challenging, so I decided to start posting free advice that just might help. The content of these pages is not endorsed by the school or the teacher. Please feel free to post comments.

Dear Students,

As we begin our intensive study of metabolic pathways, I want to give you some tips on how to approach the material, and how to get into it – or rather how to get it into you, in a useful form.

Once again your teacher has provided an outline of key terms and concepts, each followed by a small space for you to write down what the textbook says about it. The outline for this segment of the course is a formidable document: eight pages long, and consisting of close to one hundred terms. Don’t be scared. The good news is that all of these terms are functionally related to many others, like characters and events in a story. If you are reading a story (say, a serialized saga about dungeons and dragons or something), it’s fairly easy to learn a hundred interrelated terms!

There are two big stories here: Chapter 9 tells the story of how we (all eukaryotes) get energy out of food; Chapter 10 tells about how plants (or more accurately, chloroplasts) get energy out of sunlight, and how plant cells make sugar out of carbon dioxide. Forget about Chapter 10 for now. Focus on the first story: how we get energy from food.

The introduction to Chapter 9 (pages 155 – 159) tells the story in broad outline; explains why energy comes out when oxygen combines with gasoline or glucose; and introduces some key biochemical players in the drama of cellular respiration. Read it like a story; make sure that every part of it makes total sense to you. Don’t take notes, or look at the teacher’s outline, until you are done reading this intro. Enjoy. If you find yourself completely stumped by something, call a classmate to talk about it. If you are both stumped, keep going, and try to make sense of the mystery by analyzing the details.

Having the teacher’s outline in hand, you may be tempted to use it as a study guide: that is, to study by looking at each term in the outline and searching the textbook for the ‘answer.’ Don’t do this! You are not a search engine, and the textbook is not the Internet. Like all books, it is meant to be read and understood as written: each chapter is a narrative made for you to easily travel through, gathering understanding along the way.

My recommendation for taking notes as you read: use blank paper, unlined if possible. Papers should be held together in some kind of notebook. Organize ideas in the paper-space in a way that makes sense to you. Ideas can be circled or colored in for emphasis; can be connected by lines and/or color codes to show relationships; can be arrayed with other ideas, or can sit alone in wide open spaces if you know that there’s much yet unwritten about them.

Afterwards, you can go back to the teacher’s outline to make sure that you have covered everything that’s going to be on the test.

More later, as I get into my study of the metabolic pathways. (I’ve forgotten all the details, so I have to learn it again.)

Cheers,

Morgan G.