As Many Exceptions As Rules: carbohydrate

Showing posts with label carbohydrate. Show all posts

Wednesday, July 16, 2014

East To West And Back Again

Biological concepts – carbohydrates, heliotropism, monoecious, dioecious

I’m trying to think of a situation where quantity is better than

quality. Perhaps some could argue that since quality is subjective,

one person’s quality would be another person’s attempt for

quantity. In friends and experiences, I go with quality. You can

travel to every place on Earth, but if you don’t come back

changed, there was no quality. You can have many

acquaintances, but you really need only one true friend.

When it comes to the number of economically important plants, the Americas have not got many to show off. But what the two continents lack in number they make up for in quality. We have talked before about the biology of corn from North America and how it has been important for the development of molecular medicine.

Potatoes, cocoa beans, peanuts, and vanilla are also from the New World and deserve posts of their own. We’ll hear about vanilla later this summer. But one plant from the Americas has been important for food, oil, and decoration – the sunflower.

If we are going to talk about sunflowers, one question immediately comes to mind. Do sunflowers really turn to follow the sun? The answer is more complicated than it would first seem, and the answer is just part of the amazing biology of this plant.

First things first – the sunflower (genus Helianthus, about 50 species), as named in Carolus Linnaeus in 1752, does not refer to their tendency to follow the sun. Instead, he called them sunflowers because, ”Who could see this plant….without admiring the handsome flower modeled after the sun’s shape.”

Analysis of nearly fossilized human waste from the caves of Arizona (4000 BCE) show that sunflowers were an important part of the Native American diet. Sunflowers were tough, so they could grow in the Great Plains and other environments that got little rain and lots of sun. They could also grow in temperate environments. Basically, all of North America was there home.

The buffalo would trample huge swathes of land in their migrations, and the torn up ground was perfect for germination of the sunflower seeds. Slowly, this rapacious weed became a cultivated crop. Hybrids were grown, crossing prairie species with forest species and such. In modern science, the sunflower has been used extensively to study genetics of hybrids, much of this work being done at Indiana University in Bloomington, IN – my alma mater, thank you very much.

Number two - the sunflower isn’t a flower, it’s an inflorescence. This is a scientific word for a group of flowers bunched together on the same stem. We talked long ago about the Philodendron selloum inflorescence that controls it’s own temperature and gets hot to attract pollinating beetles.

Sunflowers actually have two types of flowers, the rays and the

discs. The ray florets have a longer petal, they are yellow because

bees see yellow best. The rays are fertile, and have very small

stamens and pistils that provide pollen and ovules. The disc florets,

when male, may have a sterility gene, and this makes sunflowers

very good for studying hybridizations. They also have a naturally

occurring restorer gene, so that they can again make

functional pollen.

In the sunflower, there are two types of flowers, the ray florets around the edge that every one thinks are the only flower petals, and the disc florets, which everyone assumes are the seeds. The ray florets are sterile and therefore for show only; they attract the pollinators.

The ray florets are usually bright yellow, but the disc florets are different colors in different species. They can be yellow, maroon, or even red. The red varieties all stem from a single mutation, but that isn’t the weird part. The disc florets start out male, and produce stamens and pollen, but then turn female as they mature, with the stigma pushing its way up through the middle.

This makes the flowers “perfect” and the sunflower monecious, meaning that have both male and female structures on one plant, but it also makes them smart, as the different timing reduces the chances of self-pollination (pollen and stigma aren’t around at the same time). For more discussion of monoecious (meaning “one house – male and female flowers on same plant, maybe even as the same flower as with the sunflower) and dioecious plants (male and female flowers on separate plants), see this post.

But even in this, the sunflower can be an exception. The florets mature from the outside discs to the inside discs over time. So while the inner ones may still be male, the outer ones may have become female. In times when pollinators are more rare, if a disc floret remains unpollinated, its stigma may bend down enough to touch the pollen of the still male florets more towards the center of the inflorescence! This is rare, but does occur in species that are annuals.

An achene is a type of fruit that has a hard shell and the seed is

inside. Strawberries are accessory fruits, where the accessory

organs from many achenes join together. The achenes are the

little pieces on the outside. The papery husk (exocarp) of the

sunflower achene is made from the ovary wall and protects

the seed until it is ready to germinate, like being stuck in dry,

hard, cold ground, or in the belly of a bird.

And third, the disc florets each produce a single fruit (achene), which we call (incorrectly by the way) a sunflower seed. Inside the achene shell is the sunflower seed that we eat. A single sunflower inflorescence can have as many as two thousand disc florets, so that’s a lot of fruit. In species that have more than one inflorescence, each inflorescence will have many fewer than two thousand. Flowers are energetically very costly to produce. Incidentally, almost all the wild varieties have more than one inflorescence, the domesticated versions are bred to have one.

Now for the answer to today’s question – do sunflowers follow the sun? Well, yes and no. Young sunflower plants, including the very small, juvenile flowers, have the capacity to grow very quickly. This means lots of cell growth, and the need for lots of sunlight (to produce ATP and carbohydrates by photosynthesis).

The ability to follow the source of sunlight, called heliotropism (helio = sun, and tropic = loving) requires lots of cell growth. The flower stalks don’t turn so much as they grow in a different direction. As long as the cell growth is rapid enough and the stalk is small enough to respond to changes in cell size, the plant can appear to turn.

Heliotropism is seen in many plants; they need the sun for their

very lives, so it isn’t surprising that their biology would evolve to

maximize sun exposure. The reason the cartoon uses grass – that’s

the plant in which heliotropism was first studied. What scientist

discovered this marvel of nature? Charles Darwin.

The sunlight causes destruction of a plant hormone group called auxins, so they build up in the cells of the shady side. Auxins like indole acetic acid (IAA) promote cell growth and division, so there is much more growth (longer cells and more cells) on the shady side. The uneven growth pattern makes one side longer than the other and forces the stalk to turn (see picture).

So, immature flowers will face east in the morning and west in the afternoon. But that is only part of the answer. By morning, they’re facing east again. How does that happen? A current review (2014) suggests that there may be a diurnal rhythm of several plant hormones, or a natural easterly face that is altered by light signaling. The actual mechanism for the daily turning waits to be identified.

But even this is only half the story. As the stalk gets larger and the heavy inflorescence matures, there can’t be enough cell division or hormone action for the plant to move this massive flower. The mature flowers face east all the time. But why east? Maybe they just can’t bring themselves to move one morning, and since they start out facing east, they stay that way when they give up.

Maybe, but I would imagine there’s a more biologically reason than surrender. The 2014 review cites a study that hypothesizes that facing east protects pollen from the mature florets from sun damage. Final answer, sunflowers follow the sun until it’s time to make little sunflowers, then they settle down and face the rising sun.

So young sunflowers turn with the sun, but how about another question – Why? It’s an inflorescence, not the most efficient photosynthesizer (more about this soon), so why would that structure turn to keep facing the sun? It seems like it would keep the flower in one place and turn the leaves to the sun. Hmmmm.

Now that we’ve answered the question of the day and raised another, let’s talk about the sunflower and world history. But for some unfortunate biology, you might eat sunflower roots like French fries.

The Jerusalem artichoke tuber (top) looks a little like ginger root,

but it is sweeter and not so fibrous. See the text for why you almost

grew up eating McDonald’s sunchoke fries instead of potato fries.

One species of sunflower, Helioanthus tuberosus, has an edible tuber root that is often called a Jerusalem artichoke. Since the sunflower is from North America, you know that the Jerusalem part of the name is wrong. And it’s not an artichoke either. How it got its name

Around 1600, the Jerusalem artichoke became a popular foodstuff. Easily grown and propagated, the sunflower tuber was a great source of carbohydrates and protein. It was easy to prepare, lasted a long time in storage, and didn’t taste like dirt or wood. Cultivation of the Jerusalem artichoke took off, and it became the primary food for many poor people and a delicacy for the rich.

The South American potato filled the same role, so who would win out as the food of the day? The Jerusalem artichoke (also called a sunchoke) had one big drawback, and it lost the battle. The potato won out, and 250 years later the great potato famine changed the immigration/emigration and ethnic patterns of the world.

What was this thing that cost H. tuberosus the war? It gives you gas. Among the many carbohydrate molecules produced by the Jerusalem artichoke is inulin. This polymer of six carbon sugars is one of those sugars that humans can’t digest, like cellulose. But our gut bacteria can.

Inulin is a branched chain of six carbon sugars. They come in several

varieties and together are called fructans. The “n” means there can be

any number of these units in the chain. They are a good source of

natural fructose, and chicory (right) is the most commercial source of f

ructans. Chicory has been used as a coffee substitute, a salad green

(endive and radicchio are types of chicory) and even in brewing beer.

In breaking down inulin, bacteria produce fructose monomers. They use these monomers as an energy source, and in doing so, produce carbon dioxide. In Central Europe, where the potato vs. Jerusalem artichoke battle was taking place, about 30-40% of the population have a genetic predilection for poor fructose absorption. This means more fructose stays in the gut….more bacteria food. This means much more carbon dioxide and …. flatulence.

In U.S. finer restaurants and gastropubs, the sunchoke is making a comeback, mostly because Americans can usually absorb fructose just fine. And the fructose helps diabetics too. Many diabetics use the high fructose:glucose ration to even out their glycemic indices.

What’s more, a 2014 study found that mice fed a high fructose diet over time do develop type II diabetes and/or fatty liver. Preceding the disease development, many specific genes change their expression patterns. If their diet was supplemented with extract from Jerusalem artichoke, many of the genes showed normal expression, and the diseases did not develop. Not bad for a sun chasing flower.

Next week, another question to investigate - what/who makes the loudest noise in life?

Vandenbrink JP, Brown EA, Harmer SL, & Blackman BK (2014). Turning heads: The biology of solar tracking in sunflower. Plant science : an international journal of experimental plant biology, 224C, 20-26 PMID: 24908502

Chang WC, Jia H, Aw W, Saito K, Hasegawa S, & Kato H (2014). Beneficial effects of soluble dietary Jerusalem artichoke (Helianthus tuberosus) in the prevention of the onset of type 2 diabetes and non-alcoholic fatty liver disease in high-fructose diet-fed rats. The British journal of nutrition, 1-9 PMID: 24968200

Wednesday, September 18, 2013

It’s Not Just Our Tooth That’s Sweet

Biology concepts – homochirality, carbohydrates, chiral discrimination, glycoside, H antigen

It isn’t just biomolecules that show chirality. There is also

chiromorphology, like snail shells that usually turn to the right

(dextral, or D-). There are factors in early embryonic

development that cause the body and shell to be right handed

in most gastropod species, yet other species are left handed.

There are also instances where a right-handed species will

produce a left-handed individual, so shell collectors have to be

on the look out for abnormal individuals.

A couple of weeks ago we talked about how, in most cases, life uses exclusively the left-handed enantiomers of amino acids to make proteins. This homochirality is also see in the sugars we talked about last week, but in this case, mostly D-sugars are utilized in biological systems.

What isn’t amazing is that it happens to be L- for amino acids and D- for carbohydrates; the fact that they’re different is no big deal. Evolution just wants the parts to fit together, so if an enzyme evolved to use D-sugars, it’s not a surprise that the D-sugar would be favored in the pathway then now on.

But it might not have been random either. No one knows for sure, but hypotheses abound for how homochirality in these biomolecular monomers was established.

One 2009 paper was concerned with the maintenance of homochirality rather than its establishment. Dr. Soren Toxvaerd stated that if you don’t believe life as we see it today occurred in a singular event, then it must have developed over a long period of time. Evidence indicates that small changes in the self-assembly of biomolecules took place over at least thousands of years.

If life took a long time to develop, then prebiotic (before life) earth must have been fairly stable in terms of enantiomer concentrations. But we know that homochiral solutions will turn to racemic mixtures (containing both L- and D- enantiomers) in a short time, days for amino acids and just hours for sugars. So how could the environment have been stable enough for life to develop over time?

One possible hypothesis about the establishment of homochirality

was put forth in 2010 by Koji Tamura, PhD in the Journal of

Cosmology. Put very simply, RNA may have developed before

proteins. RNA evolved to use only D-ribose because a mixture

would have been a symmetry violation. The action of D-ribose

would have been driven toward L-amino acids because of shape

problems with attaching D-amino acids to tRNAs. Now prove it.

Louis Pasteur, he of bacteria-free milk and germ theory, may have shown us the way. He discovered chiral discrimination. Racemic mixtures, under the right conditions, will separate into pools of homochirality. There is an energy gain and stability to packing homochiral molecules together; the other enantiomer will be excluded. This could help explain life using one enantiomer only.

What is more, hydrothermal vents and black smokers have just the needed conditions for both chiral discrimination and for self-assembly of biomolecules. Interesting huh? Think it’s a coincidence that black smokers harbor some of the oldest archaea on Earth? We may owe our very existence to plumes of superheated water and the xenophobia of enantiomers.

Lastly in this area, it may be that sugars and amino acids selected each other for homochirality. Glyceraldehyde is 1) highly discriminate for its enantiomers, 2) was present in large amounts in prebiotic oceans, 3) is used in self-assembly of many biomolecules, and 4) D-glyceraldehyde very much likes to bind to L-serine. So a slight excess in either one of these could have helped select for the other, and if this was stable, it could have caught on like “Gangnam Style.” This may be why life uses mostly D-sugars and L-amino acids and why I know the name Psy.

Now that we have delved into the mire that is maintenance of homochirality in sugars, let’s look at the rule breakers. D-sugars aren’t the only game in town.

Bacteria, oh bacteria! Once again, they lead the way in rule breaking. Last week we discussed how E.coli can generate ATP from several different sugars - glucose, lactose, etc. It takes different enzymes to metabolize each sugar, so if they are going to invest the energy in maintaining those genes and making those enzymes, there better be a good reason.

Paracoccus species 43P has been shown to have an L-glucose

metabolic pathway. This organisms is very closely related to

Paracoccus denitrificans. P. denitrificans is believed to be the

organism that was engulfed to become the eukaryotic

mitochondrion. It closely resembles the mitochondrion, and

although random genes needed for aerobic respiration have

been found in many prokaryotes, P. denitrificans is the only

prokaryote in which all the necessary genes have been found.

A 2012 study tried growing soil bacteria on medium that contained only L-glucose as an energy source. One species of bacterium, Paracoccus sp. 43P, was able to metabolize L-glucose to pyruvate and glyceraldehyde-3-P, and then make use that for ATP production. The researchers discovered an L-glucose-specific dehydrogenase enzyme, and this enzyme was active in the fluids from broken up paracoccus cells. The process is similar to one in E. coli, but here it is L-glucose specific.

Mammals can’t manage as well as some bacteria; we can’t metabolize L-glucose at all. However, that doesn’t mean it can't work for us. L-glucose has been proposed as an artificial sweetener, especially for type II diabetics. One form of L-glucose can stimulate insulin release, so this would be doubly good for type II diabetics. Unfortunately, L-glucose costs 50% more than gold; therefore, don't look for it next to the Truvia anytime soon.

One, but only one, study has been published showing rats metabolized L-fructose and L-gulose, but not L-glucose. From 1995, the authors waited until the end of the paper to explain that the metabolism was being carried out by the rodents gut bacteria, not by the rats themselves. No wonder it was only one paper.

Just because we can’t metabolize L-sugars doesn’t mean that we mammals are left out in the cold. Some sugars are used in the L-form even if they aren’t broken down to make ATP. The most egregious example of this is a hexose sugar called L-altrose. Why is it different than some other exceptions here? Because altrose doesn’t even occur in nature as a D-sugar; only the L-form has ever been found. It was first isolated in 1987 from a bacterium called, Butyrvibrio fibrisolvens, which is found in the GI tract of ruminate animals (cows and such).

Ruminants are mammals that have more involved digestive

strategies. Ruminants have many types of GI bacteria to help

them break down tough plant material; it isn’t surprising that

some of them can use nonstandard carbohydrates in their

physiology. “Ruminating” is the act of re-chewing food that

has been partially softened by bacterial action in the first

compartment of the stomach, and then brought back to the

mouth as “cud.” I ruminate on ideas all the time, but I think I

will stop – I’m going to call it “further thought” from now on.

Ruminates go the extra mile. They digest longer and work on food harder, using bacteria to help with much of the work. Therefore, it isn’t strange to note that L-altrose has also been seen in another ruminate bacterium, Yersinia enterolitica. Remember though, this altrose isn’t being used in energy production; it's found in their outer cell wall glycoprotein, LPS (lipopolysaccharide).

It turns out that L-sugars are common in bacterial LPS. I found examples from several different bugs, including L-quinvose (6-deoxy-L- glucose), L-rhamnose, and L-fucose (6-deoxy–L- galactose).

When it comes to L-sugars, plants can get into the act as well. Rhamnose (6-deoxy-L-mannose) occurs in nature, and can be isolated from several plants of the genera Rhamnus and Uncaria, including Buckthorn, poison sumac, and many other plants.

Rhamnose from plants takes the form of a glycoside. There’s there word again, glyco-. A glycoside in general terms is any molecule bound to a sugar. In plants, attaching sugars to create glycosides is a common way to inactivate molecules so that they can be stored for later use. When needed, the sugar residues of glycosides are cleaved away by special enzymes and then the protein, enzyme, lipid, etc. becomes active.

Digoxin (or sometimes digitalis) are cardiac glycosides from

foxglove plants. They are used to treat atrial rhythm or heart

failure problems. First used by William Withering in 1785,

digitalis is said to be the first of the modern day therapeutics.

But it can kill you too, both the plants and the drugs. A nurse

was sentenced to 18 life sentences after he was convicted of

killing more than 40 patients with digoxin.

Glycosides can be differentially regulated because there are many sugars that can be used, and several different possible linkages for each sugar/substrate combination. Therefore, cells can precisely control just when and where the glycosides are activated. This may allow cells to function for longer periods of time, but isn’t the reason that rhamnose and fucose (both L-sugars) are being included in obscenely expensive anti-aging creams.

Some evidence suggests that rhmanose and fucose can inhibit the activation of the elastase enzyme in skin cells. Elastase is known to increase in expression and activity as skin cells in culture divide several times. Therefore, companies want you to believe that rhamnose will keep your skin from looking old. Forget that keratinocytes in a petri dish bear as much resemblance to your skin as Watchmen does to Hamlet.

That was a bit sarcastic, but the cosmetic industry is a pet peeve of mine. And while I’m exposing my soul, I might as well admit to being a bit of a speciesist. I like the exceptions best when they involve Homo sapiens, so the last exception for today has to do with our own uses for a deoxy-L-sugar, fucose. I must admit that several uses of fucose apply to many mammals, but being the speciesist that you know I am, I ignore them to focus on humans.

Fucose (6-deoxy–L-galactose) is crucial for the turning of an unloved spermatozoa and a lonely oocyte into very premature teenager. Both the development and maturation of gamete cells and the development of the embryo depend on the recognition and communication of surface molecules that include fucose. But wait, there’s more.

The H antigen is linked to the red blood cell through a fucose

residue, but not in the “h” antigen mutant. Because of this, it

is not recognized for modification to the A or B antigen, and

the typical H antigen is not there to prevent development of

the H antibody.

Fucose is also a component of many glycans, including substance H. Also called the H antigen, this molecule is a precursor to the A and B antigens found on red blood cells. For people with A, B, or AB blood, the H antigen is modified to become the mature A or B antigen, but in people with O blood, the H antigen doesn’t mature and remains an H. Therefore, principal factors in every human’s development and physiology are determined in part by a sugar that we shouldn’t be using – according to the rules anyway.

However, not all is goodness and light when it comes to fucose. Some folks have a mutation in their H antigen gene that prevents its maturation to the A or B antigen. All cells would have the mutant H antigen, called h. This is different from being type O (meaning not having any A or B antigen, but still having the H antigen).

The hh or Oh blood type is called the Bombay type, and is very rare. Bombay individuals can donate blood to anyone, regardless of blood type (because they do not express any antigen to be attacked). However, because they make A, B, and H antibodies, they can receive blood only from another person with Bombay blood type. Since Bombay occurs about three times in a million births – good luck with that search for blood.

Let’s tackle the nucleic acids and their exceptions starting next week. By training I am a molecular biologist; I know an exceptional number of nucleic acid exceptions.

Shimizu T, Takaya N, & Nakamura A (2012). An L-glucose catabolic pathway in Paracoccus species 43P. The Journal of biological chemistry, 287 (48), 40448-56 PMID: 23038265

Toxvaerd S (2009). Origin of homochirality in biosystems. International journal of molecular sciences, 10 (3), 1290-9 PMID: 19399249

For more information or classroom activities, see:

Bombay blood type –

http://www.brighthub.com/science/genetics/articles/34637.aspx

http://www.youtube.com/watch?v=i5C5U8oYcHA

http://anthro.palomar.edu/blood/Bombay_pheno.htm

http://www.slideshare.net/PraveenNagula/bombay-blood-group

http://www.thinkfoundation.org/kc_bombay_blood_groups.htm

http://articles.timesofindia.indiatimes.com/2010-06-14/bangalore/28296209_1_bombay-blood-group-voluntary-donors-world-blood-donor-day

Glycosides –

http://www.friedli.com/herbs/phytochem/glycosides.html

http://www.nutriology.com/glycoside.html

http://www.slideshare.net/MrSyedAmmar/saponin-glycosides

http://www.life.illinois.edu/ib/425/lecture24.html

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=37&ved=0CEgQFjAGOB4&url=http%3A%2F%2Fpollen.utulsa.edu%2FMedical%2520Botany%2Fglycosides.ppt&ei=AzIJUtzcIcf4yAHN_YCIAQ&usg=AFQjCNF-4CagvaFEEl6GWgvsQovlsXpqaA&sig2=aTIuJ7Vho69FR4g_zqyI5A&bvm=bv.50500085,d.aWc

Racemization –

http://pubs.acs.org/subscribe/archive/tcaw/10/i02/html/02brignole.html

http://www.youtube.com/watch?v=g0qZ6BDRsZI

http://journalofcosmology.com/SearchForLife108.html

Wednesday, September 11, 2013

Sugars Speak In Code

Biology concepts – carbohydrates, monosaccharides, hexose, glycocode, starch, glycogen, carbohydrate linkage, bacterial persisters, fructolysis

Refined sugar is produced from two main sources, sugar cane (37

different species of grass from the genus Saccharum, bottom right),

and sugar beet (Beta vulgaris, top right). Sugar cane accounts for

80% of the sugar produced today. The cane or the beets are ground

and the sugary juice is collected with water or on its own. To refine

the sugar, which still has molasses from the fiber, is processed with

lime or soda and evaporated to produce crystals. The color is

removed by activated charcoal to produce the white sugar we most

often see (top middle). Brown sugar is sugar in which the molasses

has not been removed and still coats the crystals (bottom middle).

Unprocessed sugar from cane is shown on the bottom right, while raw

sugar (not whitened) is on the top right.

It would be hard to argue that without sugars, none of us would be here. Glucose provides us with short and medium term storage of energy to do cellular work, but would you believe that certain parts of reproduction use a completely different energy source. All hail fructose!

Sugars are better termed carbohydrates, because they are basically carbon (carbo-) combined with water (-hydrate). The general formula is C_n(H₂O)_n; for instance, the formula for glucose is C₆H₁₂O₆.

The simplest sugars are the monosaccharides (mono = one, and sacchar from the Greek = sugar. They can be composed of 4-7 carbons, called tetroses (4 carbon sugars), pentoses (5), hexoses (6), and septoses (7).

Things aren’t so simple though, even for the simple sugars. Let’s use the hexoses as an example, although what we say will also apply to the other sugars. We said the formula for glucose is C₆H₁₂O₆, so that makes it a hexose. Is it the only hexose – heck no! Hexoses can be aldoses or ketoses, depending on their structure (see picture). Even more confusing, -OH groups can be located on different carbons making them act different chemically.

This chart is a brief introduction to the complexities of simple

sugars. They can vary in the number of carbons (triose vs.

pentose vs. hexose. They can also vary in their structure even

if they have same number of carbons (glucose vs. galactose).

Yet another difference can come in their reactive group on the

end, being either a ketone group (ketoses) or an aldehyde

group (aldoses).

There are actually 12 different hexoses – some names you know; glucose, fructose, or galactose. Others are less common; idose, tagatose, psicose, altrose, gulose – you won’t find those in your Twinkies. Then there are the deoxysugars, carbs that have lost an oxygen. Fucose is also called 6-deoxy-L-galactose, while 6-deoxy-L-mannose is better known as rhamnose.

If this wasn’t difficult enough, stereoisomers again rear their ugly head, as it did last week with the proteins. Hexoses have three (ketoses) or four (aldoses) chiral carbons each so hexoses can have eight or 16 stereoisomers! Every isomer may act differently from every other; this allows for many functions. But wait – there’s more trouble when we start linking sugars together.

Simple sugars can be joined together to build disaccharides (two sugars), oligosaccharides (3-10), and polysaccharides (more than 10). The subunits are connected by a hydrolysis reaction. Just like with the amino acid linkages in proteins, a water molecule is expelled when two sugars are joined together. Sucrose (table sugar) is a disaccharide made up of a glucose linked to a fructose.

Just where the linkage takes place is also important. Our example again can be glucose. Many glucoses can be linked together with an alpha-1,4 linkage. Long chains of glucoses linked in this way are called starch or glycogen, based on the different branching patterns they show. Mammals store glucoses as glycogen, while plants store them as starches.

Amylose is one type of starch, amylopectin being another.

They are different from celluloses only by the way the sugars

are linked together. You can see that in starch the CH2OH

group are all on the same side, while in cellulose they alternate.

This may seem like a small difference, but we can digest only

starch (or glycogen, which has the same type linkages),

not cellulose.

Humans can digest both starch and glycogen because we have enzymes that can break alpha-1,4 linkages. But if you change the chemical shape of the bond (see picture) to a beta-1,4 linkage, the glucose polymer becomes cellulose.

Plants make a lot of cellulose for structure, but even though it is made completely of glucose, humans can’t digest it at all! Ruminate animals can digest cellulose, but it takes some powerful gut bacteria to help out, and one of the side effects is a powerful dose of methane. Cows are the greatest source of methane on the planet!

We have talked about carbohydrates as energy sources, but pretty much every biological function and structure in every form of life involves carbohydrates.

Carbohydrates are important structural elements. Cellulose, thousands of beta-1,4-linked glucoses, help give plants their rigidity, especially in non-woody plants, but in woods as well (linked together by lignin). As such, cellulose is by far the most abundant biomolecule on planet Earth.

Chitin is another structural carbohydrate. Chitins make up the spongy material in mushrooms, and the crunchy stuff of insect exoskeletons. You don’t get much more structural than keeping your insides inside.

Carbohydrates are often part of more complex molecules as well. Nucleic acids like RNA and DNA have a five-carbon ribose or deoxyribose at the core of their monomers. Glycolipids and glycoproteins (glyco- from Greek, also means sweet) are common in every cell. Over 60% of all mammalian proteins are bound to at least one sugar molecule.

The different sugar-linked complexes are part of the glycome (similar to genome or proteome), including oligo- and polysaccharides, glycoproteins, proteoglycans (a glycoprotein with many sugars added), glycolipids, and glycocalyxes (sugar coats on cell surfaces). None of these carbohydrate additions are coded for by the genetic code, yet a great diversity of glycomodifications are found on most structures of the cell.

The carbohydrate code is still a mystery to us. The glycosylation can be

linked together by N-type or O-type linkages, the order of the sugars

can vary, the numbers of each type of sugar can vary, and the branching

can vary. Every difference adds to the complexity of the code and can

direct a different message to the cell or the molecules with which

these glycans come into contact.

The diversity and complexity of these added carbohydrates is highly specific and highly regulated – this is the glycocode or carbohydrate code. Yet, we haven’t even come close to breaking the code, i.e., what series of what sugars means what.

The glycocode is important for cell-cell communication, immune recognition of self and non-self, and differentiation and maturation of specific cell types. Dysfunction in the glycocode leads to problems like muscular dystrophy, mental defects, and the metastasis of cancer – we better get cracking on the code breaking.

In the middle of 2013, a new method was developed for detecting the order and branching of sugars on different molecules. This method uses atomic force microscopy (AFM) to actually bump over the individual sugars on each molecule and identify them by their atoms, even on live cells. I’m proud to say that my father-in-law played a role in developing AFM for investigation of atom distributions on the surfaces of solid materials, mostly superconductors.

The glycome is even more diverse because different types organisms make different sugars. One thing I find interesting is that mammals don’t make sucrose. No matter what we mammals do, we won’t taste like table sugar when eaten – more’s the pity. I wonder what a sweet pork chop might taste like.

Proof that many foods have sugars – the Maillard reaction. That gorgeous

browning of your bread or steak comes from a chemical interaction

between the sugars and amino acids of the food. In the process, hundreds

of individual different compounds are made, each with a different flavor

profile. The example in the chart above is for caramelizing onions. Each

food and its chemical make up produces a different set of Maillard

products. You roast your coffee beans for the same reason. This is why

Food Network always suggests ways for you to get great searing and

browning of food.

We use sucrose as sugar because it is relatively easy to obtain from the plants that do make, like sugarcane or sugar beets. Fructose (often called fruit sugar) is actually sweeter on its own; almost twice as sweet as sucrose and three times as sweet as glucose. This explains why so many sweetened foods are full of high fructose corn syrup (go here for our previous discussion of high fructose corn syrup).

We all know that organisms use glucose as an energy source, first through its breakdown to pyruvate via glyceraldehyde -3- phosphate (G3P) in glycolysis; the pyruvate then travels through the citric acid cycle to produce enough NADH and NADPH to generate a lot of ATP. But fructose can be used as well.

Fructose undergoes fructolysis, different from glycolysis only in the fact that one more step must be taken to generate G3P (adding the P to G3 is done by the enzyme trioskinase). In humans, almost all fructose metabolism takes place in the liver, as a way to either convert fructose to glucose to make glycogen, or to replenish triglyceride stores – so be good to your liver.

The big exception is how important fructose is in mammalian reproduction. Spermatozoa cells use fructose as their exclusive carbohydrate for production of ATP while stored in the testes. This fructose comes not from the diet but the conversion of glucose to fructose in the seminal vesicles.

Why use a different carbohydrate source just for sperm? Seminal fluid is high in fructose, not glucose. Perhaps this is a factor in seminal fluid viscosity. If this problem is solved using fructose, then the cells swimming in it would probably switch evolve to use it as an energy source.

I asked Dr. Fuller Bazer of Texas A&M about this and he pointed out that fructose can be metabolized several different ways, and some of these lead to more antioxidants and fewer reactive oxygen species - it would be important to leave sperm DNA undamaged, especially since we have previously talked about how they are more susceptible to oxidative damage.

Bazer also pointed out that unlike glucose, fructose is not retrieved from tissues and put back into circulation. Once it’s sequestered to the male sexual accessory glands, it would stay there. Still lots to be learned in this area.

Fructose is sweeter than glucose. Sucrose is one glucose joined to one

fructose, so the ratio is 50:50. In most honey, the fructose:glucose ratio

is about 55:45, so it is often sweeter than table sugar. Since it is higher

in fructose, some people liken it to high fructose corn syrup, but there

are many compounds in honey that also help the immune system, etc.

However, recent evidence is showing that some honey is being diluted

with high fructose corn syrup and some bees are being fed HFCS. The

benefits from true honey are then lost.

A 2013 study shows that maternal intake of fructose can also affect reproduction. Pregnant rats fed 10% fructose in their drinking water had significantly fewer babies, but a greater percentage of the offspring were male (60% versus 50%). The fructose did not arrest female embryos from developing or have a sex-specific effect on sperm motility, suggesting that the sugar has a direct effect on the oocyte that increases the chances of being fertilized to produce a male. Weird.

Using sugars other than glucose may be a big deal for mammals, but bacteria can thrive on many different sugars. E. coli can process glucose, but if other sources of sugar are around, they will switch over in a heartbeat – if they had a heart. E. coli has a whole different set of genes for lactose metabolism, found in something called the Lac operon. The operon gets turned on only if lactose is present and glucose is not.

The ability for bacteria to use other sugars might save us as well. Some bacteria can just shut down their metabolism if antibiotics are present and just hangout until the drugs are gone. These are called persister organisms, and they are different from antibiotic resistant bacteria. A 2011 study showed that if you give sugar in combination with some kinds of antibiotics, the persisters just can’t resist the sweet treat and will not shut down their metabolism. The antibiotics then become effective. Using sugars we don't metabolize, like fructose or mannitol, ensures that they will be around to help kill the bacteria. Amazing.

We have just brushed the surface of sugary exceptions. Next week we will see how nature first selected a single type of sugar to use in biology, and then went right out and broke its own rule.

Gunning AP, Kirby AR, Fuell C, Pin C, Tailford LE, & Juge N (2013). Mining the "glycocode"--exploring the spatial distribution of glycans in gastrointestinal mucin using force spectroscopy. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 27 (6), 2342-54 PMID: 23493619

Gray C, Long S, Green C, Gardiner SM, Craigon J, & Gardner DS (2013). Maternal Fructose and/or Salt Intake and Reproductive Outcome in the Rat: Effects on Growth, Fertility, Sex Ratio, and Birth Order. Biology of reproduction PMID: 23759309

Allison KR, Brynildsen MP, & Collins JJ (2011). Metabolite-enabled eradication of bacterial persisters by aminoglycosides. Nature, 473 (7346), 216-20 PMID: 21562562

For more information or classroom activities, see:

Testing for carbohydrates in foods –

http://www.elmhurst.edu/~chm/vchembook/548starchiodine.html

http://www.chemheritage.org/percy-julian/activities/10a.html

http://www.biotopics.co.uk/nutrition/amylex.html

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=8&ved=0CGAQFjAH&url=http%3A%2F%2Fwww.aug.edu%2F~tcrute%2Flab_experiments%2F1152-experiments%2F1152%2520lab-carbohydrates.doc&ei=u4oKUpbwEcWv4AOC54GgDA&usg=AFQjCNGJ6RG1F3kq2fOfURP3iWmVkyZ7XA&sig2=FeyhQdadG56uKmNx3xBL8A

http://www.hometrainingtools.com/starch-test/a/1497/

http://bioweb.wku.edu/courses/Biol114/Online/Carbo/carbo1.asp

http://seplessons.ucsf.edu/node/362

http://bioweb.wku.edu/courses/Biol114/Lab1.asp

Structures of carbohydrates –

http://nhscience.lonestar.edu/biol/biolab/carbos.htm

http://www.wisc-online.com/objects/ViewObject.aspx?ID=AP13104