As Many Exceptions As Rules: 2013

Monday, December 23, 2013

Twelve Days Of Christmas – Biology Style

Biology concepts – introduced species, cross breeding, courtship rituals

We are finishing a long series stories on sleep and activity patterns, but I thought we might take a break and talk about the holidays. How about a couple of posts concerning the ways Christmas can be viewed biologically? We will return to activity patterns and Hawaii after the new year.

Lets examine the carol, “The Twelve Days Of Christmas.” Initially published in England in 1780, it was probably a British memory game before it was a carol, but older versions in France suggest that it came from that country originally. The twelve days of the lyric are from Christmas Day to the Epiphany (the baptism of Jesus of Nazareth).

Many interpretations of the song exist, from the devoutly religious to the idea of managing a country estate. For our purposes, lets stick to biological explanations of the gifts. Keep in mind that they were given by one’s true love; many have to do with family, love, and faithfulness – sounds more like a warning than a gift to me.

There are four subspecies of red-

legged partridge: French, Spanish,

southern Spanish, and Coriscan.

The English version is the Corsican,

even though it was imported from

France.

A partridge in a pear tree – A partridge is a small game bird, a member of the pheasant family. The red-legged partridge is an introduced species; it was brought to England from France in the 1600’s as target practice for Charles II. The red-legged partridge is known to roost in orchards, including pear trees - hence the pairing of the gifts.

This bird is exceptional in that it often lays eggs in two different places. The female incubates one clutch while the male incubates the other. Their loyalty, devotion to family, and fidelity are plausible reasons for their inclusion in the song. This is further supported by another behavior of the female partridge. She will feign injury to draw the attention of a predator and protect her babies.

Two turtle doves – These members of the dove family are also a symbol of devoted love, since the males and females were imagined to mate for life. This turns out not to be true, as a study in 2008 shows that the hens will mate with bachelor males as well as males from other bird species. These hybrid crosses in other animals often result in non-fertile offspring (like mules, which are crosses between horses and donkeys), but the offspring of dove crosses are often fertile.

The Crevecoeur chicken is much like

the Houdan, but the Crevecoeur only

has four toes!

Three French hens – This might refer to cross-bred chickens. In the 1600’s, chickens were brought to France from the East and bred with French poultry. The Crevecoeur (named for the town in Normandy) breed is probably related to the Polish breeds. The very ornamental Crevecour is now only bred for poultry shows and is not eaten. Two other french breeds (three total) also originated around this same time, perhaps this is why they were used for the third gift.

Some believe that the chickens were included in the song because a rooster crowed at the birth of the baby Jesus. So shouldn’t the gift in the song be three French roosters? More likely it was because the hen represented motherly devotion and love.

Four calling birds –History suggests that calling birds was actually “collie birds,” another name for blackbirds (collie came from coal, as in coal-y = black like coal). The blackbird is a true thrush, common to most of western Europe. These were fairly common birds in the 1700’s, and were trapped in barns and the like to supplement the diet. They became a delicacy.

While the first four gifts all refer to birds, only the first three bring connotations of love and fidelity. The fourth is mostly commonly associated with eating. Which of these things is not like the others?

The male pheasant has the golden rings.
Does he give one to the plainer female during
courtship? Male ornamentation is common
in lower animals; in humans it looks silly,
pinkie rings and a one earring.

Five golden rings – Maybe we were just starting a new pattern, since the five gold rings also refers to eating a bird. Golden pheasants have five or more golden rings on their necks, and they were often served at royal and other high society feasts.

Pheasants and partridges are closely related; they come from the same family of Phasinidae. While they are very different in size (about 7 inch quails to 30 inch pheasants), they both have short, powerful legs that allow they to run quickly along the ground to elude predators.

Giving your true love five gold rings is overkill anyway, right?

Six geese a-laying – Still with the birds - how is it that the Audubon Society hasn't adopted this song as their anthem? In the carol, the geese may serve two purposes. One, they were bred for better egg laying, up to 50 eggs per year. This made them symbols of fertility. Second, they were often served as Christmas dinner – remember the prize goose the reformed Scrooge purchased for the Cratchits.

The indigenous wild boar was originally the choice for Christmas feasting, but was hunted to extinction on the island by the 13^th century. It was reintroduced later, but turned into a nuisance by eating all the crops. Consequently, it was hunted to extinction in England again by the late 1700’s. Imagine the kind of protests that would occur nowadays if a species was about to be eliminated for second time in the same place! Even today, a string of sausages is often placed around the goose’s neck as a reminder of boar’s place on the table.

The male (cob) and female (pen) swan will

mate for life. If one dies, the other will remain

alone for the rest of its life.

Seven swans a-swimming – Because swans could both swim and fly, they were revered in many ancient cultures. Waterfowl (Anatidae family, includes ducks, geese and swans) may have evolved from the galliformes (order including chickens and our friends the pheasants and partridges). This is the majority opinion, but some scientists believe that they descended from shorebirds. This is believable, they already lived on the shore; it was a short trip to adapt to the water.

King Edward used swans in his coronation in 1304, and other royal families then adopted their use across Europe. As such, all swans in public were the exclusive property of the monarch (landowners could have some on their property), and were seen as precious, just like the adoration of your true love. Oh, and they ate them at Christmas too. Apparently, during this time period, the way to another’s heart was through their stomach, and birding.

Personally, I think of Edward Jenner when
milkmaids are mentioned. He recognized that
they didn’t get smallpox, only coxpox. He used
this knowledge to develop a smallpox vaccine.

Eight maids a-milking – The first seven gifts were all birds, but the last five gifts are all humans. Is that a step up or a step down? As for the milkmaids, we have two ideas implied; one is food, and the other is romance (or just lust).

In the 1700’s there was no refrigeration, so milk products were short-lived and therefore precious. Giving a loved the ability to have fresh milk would mean many holiday treats, like custards and cheeses. Food and banqueting are sure playing a big role in this song.

The other use of this gift is slightly less savory. In France, the milkmaid was a sign of fertility; big-busted and fit. In England, to ask a young lady to go a-milking could be a legitimate proposal of marriage, or an illicit proposal of hanky-panky. Either way you take it, this is a loaded gift, biologically-speaking.

Nine ladies dancing – The rest of the gifts have to do with musicians and dancers. Basically, the gift-giver was hiring a band and entertainment for his/her true love's banquet.

Dancing is often considered the human equivalent of sexual selection behavior in animals. Indeed, the psychologist Geoffrey Miller deduces that human culture of all types developed as a type of sexual selection, which, along with natural selection, forms the basis of evolution.

Is this a female or a male squinting bush

brown butterfly? What if I told you it has

been warm and rainy the past few weeks.

Females dancing as a courtship ritual is an exception. Usually males display and try to draw the attention of the female. However, in one species of cichlid fish, the striped kribensis, the females do dance for the males, brushing their large pelvic fins against the male. Males will most often select the females with larger pelvic fins.

Other species will have the females dance – sometimes. In the squinting bush brown butterfly, it all depends on the temperature when the caterpillars mature. If cool, then the females will develop large ornamental spots and will dance to attract males. If they mature in warmer, moist conditions, the males will have the spots and will dance for the females.

Ten lords a-leaping – The males of many species dance as a part of courtship. Jumping spiders have an elaborate dance that is meant to show off their iridescent hairs and bright abdomen. They also vibrate or twitch their abdomens and legs (click for a video link) to make a purring sound as well. Grebes (birds) have a mutual dance and run that the male and female perform together, both as part of initial mate selection, and then repeated to reinforce their bond (click for video).

In a positron emission tomographic (PET) image,

yellow and red mean more activity. Notice how words

(bottom left) and music (bottom right) seem to

activate different parts of the brain. Pleasant music

activates positive emotional centers.

Eleven pipers piping – Commonly, the pipers are shown to be playing flute or other recorder-type instruments, but I think that the bagpipes might be more accurate historically. The best biology I can do for the bagpipes is that they are supposedly a source of music, they are meant to generate positive emotions – music soothes the savage beast. PET scans confirm that dissonance in music activates the negative emotion centers of the brain. For me, the pipes are quite dissonant.

Twelve drummers drumming – This final gift may relate to the rhythm of the drums. Anthropologists talk about drumming in terms of emulating the beating heart. This brings us back to romance and love, and in a sense, drums are then the truest form of biological music.

If we return to the banquet motif that has pervaded so much of the gift giving here, drums were late coming to England and Europe. They were teamed with the trumpets that would announce the arrival of the next course during the banquet. How could they possibly notice the next course with all those ladies dancing, lords leaping, and pipers piping, not to mention all the birds hanging around?

You probably didn’t realize there was so much biology in a Christmas song - but biology is everywhere. Next time we will investigate the biological aspects of a few random holiday traditions. For example, in many lizard species virgin births are no big deal.

All the concepts here will be explained in more detail in the near future, resources for each will accompany their explanations.

Wednesday, December 11, 2013

Is There Anything Fat Can’t Do?

Biology concepts – lipid, phospholipid, eicosanoid, sterol, unsaturation, omega fatty acids, essential fatty acids, fluid mosaic model, lipid droplets, myelination

Last week we talked about fat, but fats are just one of the many lipids in living organisms. Lipids are the fourth of our four biomolecules; we’ve already discussed proteins, carbohydrates and nucleic acids. Lipids may be last, but they're certainly not least.

Basically, all fats are lipids, but not all lipids are fats. The players are varied both in structure and function. Fats are three fatty acids + glycerol, but lipids are any of a group of organic compounds, including fats, oils, waxes, sterols, and triglycerides. The unbroken rule is that all lipids are insoluble in water, soluble in nonpolar organic solvents, and oily to the touch.

This cartoon shows the plasma membrane of a typical

cell. Water on the outside (exoplasmic face) and inside

(endoplasmic face) next to the outer and inner leaflets

of the bilayer. The hydrophobic and hydrophilic regions

are set by the structure of the phospholipid, shown bigger

on the right. The little + shows where the head molecule

is, and the _ sign is where the phosphate is (hence the

name phospholipid). The two fatty acid tails can be the

same or different, here they are same (count the

carbons in grey).

All lipids are made from fatty acids – although only about half are recognizable as fatty acid products. Fats are a glycerol molecule with three fatty acids attached, but phospholipids are usually a glycerol with just two fatty acid chains. The third glycerol position is taken by the head molecule of the phospholipid. The common heads are choline, ethanolamine, and the amino acid serine. Yet another non-protein function of an amino acid.

Phospholipids spontaneously form lipid bilayers (see picture) and spherical hollow spheres, which are perfect for making cell membranes. The heads are hydrophilic (hydro = water, and philia = loving) while the fatty acid tails are hydrophobic (phobia = fear). This makes for a potent cell membrane, keeping the large water-soluble molecules inside the cell because they won’t pass through the hydrophobic tail region. Notice how the two hydrophilic regions face water, while the two hydrophic portions of each layer hide on the inside.

The cell membrane isn’t made of only lipids; there are thousands of different proteins that perform many functions – signaling, receiving chemical messages, acting as channels and transporters for different molecules that can’t make it through the membrane on their own. There are also some other lipids in the membrane that we will talk about in a minute.

Sphingosine is the backbone for sphingolipids, but it has

other functions as well. S1P stands for sphingosine-1-

phosphate, and important molecule in membrane signaling.

You can see some of the players here, Akt, Rac, Src and

other second messengers are phosphorylated and

phosphorylate other molecules to pass the message

along. Here the message is about whether the cell should

move (migrate). The shown pathways are just the

start of the response.

Of course there are exceptions within the phospholipids. Triglycerides and phospholipids are built on a glycerol backbone, but sphingolipids are based on a molecule called sphingosine. Sphingomyelin (the head is choline) is considered a phospholipid because it functions similarly, but it is structurally different and has only one fatty acid tail.

Sphingolipids also sit in membranes, but they are usually asymmetric. This means that there are usually more of these in the outer layer of the phospholipid bilayer, also called the outer leaflet. From here they participate in a lot of the signaling through the membrane and in protecting the membrane from damage. When the cell is damaged and needs to commit suicide (apoptosis), divide, reduce its function (senescence), or differentiate (change what type of cell it is), part of the signaling will go through the sphingolipids.

The fatty acids that make of the hydrophobic tails of phospholipids and sphingolipids can vary; even the two fatty acids on a single phospholipid can be different. One of the most common phospholipids is DPPC – dipalmitoylphosphatidylcholine. This means the head molecule is phosphocholine, the backbone is glycerol, and the two fatty acids are both palmitic acid, a fatty acid with no double bonds (saturated) and a chain of 16 carbons.

Palmitic acid itself is designated as C16:0, meaning it has 16 carbons and zero double bonds; oleic acid is C18:1, and so on. Fatty acids of two to 36 carbons have been found in nature, with many variations as to the number of double bonds.

These are typical fatty acids found in most cells. Palmitic

is one of the most common in the fatty acids of membranes.

You see that the more double bonds (all cis- here) they

have, the number after the colon, the more they bend.

Arachidonic acid is a veritable contortionist. Erucic is one

of the lesser common fatty acids, it is important in Lorenzo’s

oil, a treatment for adrenoleukodystrophy, and the subject

of the movie of the same name.

Oddly, fatty acids with an odd number of carbons are rare in mammals. Our system of producing fatty acids works by adding carbons two at a time, so the products are usually even numbered. Breaking down fatty acids is also done two at a time; oxidation of odd chain fatty acids requires three extra enzymatic steps. That’s a waste of resources, so we stick to even numbers.

But there are exceptions. Ruminant animals have about 5% odd chain fatty acids, much more than other mammals. Why would this be?

What if I told you that bacteria and plants have lots of odd chain fatty acids? Ruminants (cows and such) have lots of bacteria in their numerous stomachs; the microbes help break down the plant cellulose of the ruminants’ plant diet. Naturally, some of these odd number FAs get incorporated into the animals’ tissues. A 2012 review pieced together the evidence so that changing levels of odd chain fatty acids in the stomachs of cows could be used to predict rumen health. More of C17:0 for instance, might indicate a rumen acidosis.

Free fatty acids (FFA) are attached to nothing, and rarely found on their own. In fact, they can be toxic in high concentrations. However, when we break down triglycerides to burn for energy, the fatty acids are released as FFA, so a low level can be found in the blood. Does that mean it's bad to lose weight too quickly; could you release so much FFA that you toxify yourself? Exercise might be dangerous!

Free fatty acids are also referred to as unesterified fatty acids.

It is an ester bond that attaches them to the glycerol molecule

in a triacylglycerol (fat) molecule. Here is one pathway where

they work to increase sugars in the blood (hyperglycemia).

This is one way FFA are said to lead to obesity and type II

diabetes. They also have effects on the insulin producing cells.

FFAs can be trapped in cells and membranes. FFAs are broken down through a process called lipid peroxidation, releasing free oxygen radicals that can damage the cell. This is thought to be important in development of obesity-related type II diabetes, since the insulin producing beta cells of the pancreas are targeted by FFAs. I don’t know why the FFAs target the beta cells – that could be your ticket for a Nobel.

Here comes an exception - heart and skeletal muscle actually prefer to use FFAs as energy sources as compared to glucose! This may be due to the higher energy storage potential of fatty acids, these high energy demanding tissues can get more bang for their buck by using fatty acids. The difference is that these fatty acids are usually bound to albumin in the blood, so they are not toxic like free fatty acids.

We humans can make most of the fatty acids they need. But, as with amino acids, there are a couple that we must get from our diet. These are the essential fatty acids, linolenic (C18:3n-3) and linoleic (C18:2n-6). The terminology is getting deep, but these are the omega three and omega 6 fatty acids. We can’t make double bonds beyond the #9-10 carbons in a fatty acid chain, so the omega fatty acids have to be brought on board by eating fish and plant oils (see the picture above).

Here are some good sources of essential fatty acids, the

omega-3 and omega 6 fatty acids. Rapeseed and olives are

among the vegetable oils that are high in essential fatty

acids, as well as the oily fishes (salmon, herring, mackerel)

and nuts. I never thought of eggs as particularly good

sources, but there they are. Apparently hens raised on

greens and insects have more essential fatty acids in their

eggs as compared to hens fed grains.

Recently, evidence is piling up that omega 3 fatty acids are excellent for preventing and treating depression. A 2013 review indicates that omega-3’s are good for treating major depressive disorder. Another 2013 study showed that the number of self-reported depressive symptoms in American women are inversely proportional to the amount of omega-3 fatty acids consumed in their diet. Eat fish to be happy!

The essential fatty acids + arachidonic acid (20:4n-6) are also important for constructing another form of lipid – the eicosanoids (including the prostaglandins, thromboxanes and prostacyclins and leukotrienes). However, eicosanoids are so modified that it would be hard to tell they were based on fatty acids. These lipids are essential for the function of the immune system, including controlling inflammation, clotting, pain, and fever.

The exception to this is the endocannabinoids. These molecules do work in inflammation, but also have a lot to do with regulating mood and behavior. This may be why essential fatty acids are important in treating depression. You have probably noticed that the word (and structure) of the endocannabinoid bears resemblance to the active ingredient in marijuana – tetrahydrocannabinol (THC). This may also reflect their mood altering capabilities.

The final group of lipids we will talk about are the sterols. These (and the cardiolipins) are based on ring structures (see picture), having started out as fatty acids. The functions of sterols are many and diverse. They serve in hundreds of different signaling systems as a major class of hormones (like the sex hormones testosterone and estradiol and the metabolic hormone cortisol).

On the top you can see how the cholesterol (yellow) breaks

up the monotony of the phospholipids. The space makes it

easy for proteins and lipids to flow – hence the fluid mosaic

model. This is shown better in the bottom cartoon. The #2

shows a lipid raft, made with phospholipids with longer tails,

and similar proteins to do similar functions. These rafts can

move around to where they are needed on the surface, break

up and reform later, all because the elements of them are

fluid. Thank you cholesterol.

Cholesterol is also a sterol lipid. I know that cholesterol gets a bad rap, but you don’t own a single cell that can survive without it. It's the "other lipid" in the lipid bilayer, serving to maintain the fluidity of the membrane. Part of the fluid mosaic model, cholesterol inserts itself into the bilayer and keeps the chains of the phospholipids from becoming entangled. They also work with the proteins to allow for movement around the cell surface.

So those are the lipids - definitely necessary for long-term energy storage, but also crucial for cell integrity and nearly every other function in an organism. Just to highlight this, let’s look at two very different functions of lipids.

Your brain just don’t work good without lipids! Many of your neurons have a lipid coating around them called myelin. The electrical impulse travels down the neuron in an unmyelinated neuron (grey matter), but can jump from the gap to gap (called nodes) in a myelinated neuron (white matter). This makes for much faster processing of neural signals, and is the only reason we can function at the level we do.

Trouble with lipid storage and function (called lysosomal lipid storage diseases) will mess with myelination. Diseases like Gaucher’s disease and Niemann-Pick both have myelination problems, and can result in severe mental retardation. These are inherited diseases, but there is an exception. Poisoning with swainsonine (from a plant called locoweed) can also result in poor lipid storage and function. It can drive cows mad (get it - locoweed), but is also a promising cancer drug.

Sphingomyelin makes up much of the myelin sheath around

the neurons – the name makes sense now, right? The Schwann

cell makes the myelin sheath by wrapping itself around the

neural axon. The electrical impulse then jumps from node to

node, making it much faster.. Not all neurons are myelinated,

just the “white matter” of the brain. Look up white and grey matter.

Lastly, lipids control your genes. Lipid droplets in your cells interact with the histone proteins that control the packaging of the DNA. DNA wrapped around histones tightly is not open to be replicated or transcribed, so no genes there can be made into protein. But a 2012 study in fruit flies showed that lipid droplets are intimately associated with proper development. Lipid droplets serve as a reservoir of histones, which can be toxic when floating freely. If lipid droplets decrease, excess histones are free to wreak havoc, and the embryo dies. Still think fats are to be avoided?

Next week, let get into the holiday spirit by looking at the biology of snow. It saved Rudolph from being a meal for some predator!

Beydoun MA, Fanelli Kuczmarski MT, Beydoun HA, Hibbeln JR, Evans MK, & Zonderman AB (2013). ω-3 Fatty Acid Intakes Are Inversely Related to Elevated Depressive Symptoms among United States Women. The Journal of nutrition, 143 (11), 1743-52 PMID: 24005610

Li Z, Thiel K, Thul PJ, Beller M, Kühnlein RP, & Welte MA (2012). Lipid droplets control the maternal histone supply of Drosophila embryos. Current biology : CB, 22 (22), 2104-13 PMID: 23084995

Vlaeminck B, Dufour C, van Vuuren AM, Cabrita AR, Dewhurst RJ, Demeyer D, & Fievez V (2005). Use of odd and branched-chain fatty acids in rumen contents and milk as a potential microbial marker. Journal of dairy science, 88 (3), 1031-42 PMID: 15738238

For more information or classroom activities, see:

Essential fatty acids –

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CCoQFjAA&url=http%3A%2F%2Fnfsmi-web01.nfsmi.olemiss.edu%2FDocumentDownload.aspx%3Fid%3D2494&ei=0r16UvnKIMKdqQH2rIGQAQ&usg=AFQjCNFOoBeS_l85BN1JdxRW44Oeq7_YUA&sig2=tOvJNx-KBKT7m_nKzvwpEg&bvm=bv.55980276,d.aWM

http://www.lessonplans.com/transitioning-chemistry-to-nutrition-the-science-behind-fats-oils/

http://exploringorigins.org/fattyacids.html

http://classroom.synonym.com/amount-epa-dha-salmon-7435.html

http://www.vegansociety.com/lifestyle/nutrition/essential-fatty-acids.aspx

http://umm.edu/health/medical/altmed/supplement/omega3-fatty-acids

http://www.jbc.org/content/287/42/35439

http://recipes.howstuffworks.com/what-are-essential-fatty-acids-and-can-you-get-them-without-eating-fish.htm

http://www.news-medical.net/health/Linoleic-Acid-What-is-Linoleic-Acid.aspx

http://www.webmd.com/vitamins-supplements/ingredientmono-1035-ALPHA-LINOLENIC%20ACID.aspx?activeIngredientId=1035&activeIngredientName=ALPHA-LINOLENIC%20ACID

http://www.fitday.com/fitness-articles/nutrition/healthy-eating/what-is-arachidonic-acid.html

http://www.arthritis.co.za/arachid.html

Phospholipids –

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CCoQFjAA&url=http%3A%2F%2Fwww.omsi.edu%2Fsites%2Fall%2FFTP%2Ffiles%2Fchemistry%2FNH-PDF%2FNH-C19-DNAExtraction.pdf&ei=IuF6Uq27NMOJqwHL44GYBg&usg=AFQjCNFpUTtYtLfirUu5S3DLx3JUgAXEfw&sig2=1EmmqfllcnUD1M-wg06OEw&bvm=bv.55980276,d.aWM

http://hyperphysics.phy-astr.gsu.edu/hbase/organic/phoslip.html

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Phospholipids.html

http://telstar.ote.cmu.edu/biology/MembranePage/index2.html

http://www.yellowtang.org/animations/bilayer.swf

http://www.johnkyrk.com/cellmembrane.html

http://www.d.umn.edu/~sdowning/Membranes/phospholipidlateralmovanim.html

http://bioweb.wku.edu/courses/biol115/wyatt/biochem/lipid/Lipid_2.asp

Sterols –

http://www.webmd.com/cholesterol-management/features/low-cholesterol-diet-plant-sterols-stanols

http://www.sciencedaily.com/releases/2008/07/080714165856.htm

http://www.cyberlipid.org/sterols/ster0003.htm

http://www.cs.stedwards.edu/chem/Chemistry/CHEM43/CHEM43/Steroids/Steroids.HTML

http://www.fitday.com/fitness-articles/nutrition/fats/lipids-fatty-acids-sterols-and-triglycerides-explained.html

http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb2/part1/prostag.htm

http://www.cs.stedwards.edu/chem/Chemistry/CHEM43/CHEM43/Eicosanoids/FUNCTION.HTML

http://www.heart.org/HEARTORG/Conditions/Cholesterol/Cholesterol_UCM_001089_SubHomePage.jsp

http://www.medicalnewstoday.com/articles/9152.php

http://www.nlm.nih.gov/medlineplus/cholesterol.html

http://www.healthline.com/health/high-cholesterol\

http://www.sciencedaily.com/news/health_medicine/cholesterol/

Lysosomal lipid storage diseases –

http://www.ncbi.nlm.nih.gov/pubmed/21502308

http://www.ninds.nih.gov/disorders/lipid_storage_diseases/detail_lipid_storage_diseases.htm

http://www.genedx.com/test-catalog/disorders/neutral-lipid-storage-disease-with-ichthyosis-nlsd/

http://www.genome.gov/25521505

http://disorders.eyes.arizona.edu/category/clinical-features/lipid-storage-disease

http://www.mayoclinic.com/health/gauchers-disease/DS00972

http://www.ninds.nih.gov/disorders/gauchers/gauchers.htm

http://www.news-medical.net/health/What-is-Gauchers-Disease.aspx

http://ghr.nlm.nih.gov/condition/niemann-pick-disease

http://www.parseghian.org/aboutnpc_diagnosis.html

Fluid mosaic model -

http://www.dummies.com/how-to/content/the-fluidmosaic-model-of-the-cell-plasma-membrane.html

http://www.biology-online.org/dictionary/Fluid_mosaic_model

http://www.infoplease.com/cig/biology/fluid-mosaic-model-membrane-structure-function.html

http://www.nature.com/scitable/content/the-fluid-mosaic-model-of-the-cell-14668965

http://academic.brooklyn.cuny.edu/biology/bio4fv/page/pm_mos.htm

http://www.youtube.com/watch?v=Rl5EmUQdkuI

http://www.bio.davidson.edu/people/macampbell/111/memb-swf/membranes.swf

http://www.tulane.edu/~biochem/faculty/facfigs/fluid_mosaic.htm

http://www.susanahalpine.com/anim/Life/memb.htm

http://biology-forums.com/index.php?topic=8504.0

http://biology-animations.blogspot.com/2009/09/fluid-mosaic-model-animation.html

http://i-biology.net/ibdpbio/02-cells/cell-membranes/

Friday, December 6, 2013

Request For Feedback

Good afternoon readers,

I am seeking feedback from readers and users of the blog, As Many Exceptions As Rules.

If you have read the blog and wish to express an opinion, or if you have made use of the blog in a classroom or other, I would appreciate a short e-mail detailing the ways the blog is being used.

Any feedback you have would be appreciated, either as a comment below this post or to the following address:

lasburymark1@hotmail.com

You can also send by snail mail to:

Mark E. Lasbury, MS, MSEd, PhD

5060 E. 71^st Street

Indianapolis, IN 46220

Wednesday, December 4, 2013

The Skinny On Fat

Biology concepts – lipids, fatty acid, saturated fat, trans fat, interesterification, adipose tissue, lipodystrophy, LDL and HDL

This is Lizzie Velasquez, a 24 year old with a genetic

form of lipodystrophy. She must consume 5000-

8000 calories and eat 80 times each day just to survive.

Her condition is called neonatal progeroid syndrome,

which includes premature aging and an oversized head

along with the lipodystrophy. She has dealt with more

than any person should have to, and now is a

motivational speaker – "it’s going to get better" is her

theme. Her second book, Be Beautiful, Be You is a

must read. The picture is from one of her public talks.

Most of us worry about gaining weight. We would love to be skinnier, lighter, trimmer, svelter (a new word?). But what if you had the opposite problem – you couldn’t gain any weight, no matter how much you ate?

There is a group of disorders known as the lipodystrophies (lipo = fat, dys = bad, and trophy = nourishment) in which afflicted people can't store any fat. Their stories tell us that being skinny is no blessing.

Lipodystrophies can be congenital (con = with, genitus = to beget), so they are present from conception, or they can be acquired. In congenital cases, the genetic mutation sometimes has little to do with fat, sometimes it does. There are four known mutations in four different proteins that can all lead to a lipodystrophy.

People with a congenital lipodystrophy tend to develop type II diabetes. They also get arthritis and other disorders. Some mutations also carry higher risks of mental retardation and most increase the risk of cardiac disease and cirrhosis of the liver. These can kill you.

Acquired forms often result from drug treatment. In HIV retroviral treatment, there can by lipodystrophy and lipoatrophy – which is loss of fat from one particular anatomic location, usually the face. On the other hand, visceral fat (fat around the internal organs) is increased during anti-HIV treatment. It matters, since visceral fat is associated with more heart and liver disease.

Lipoatrophy refers to the loss of fat in a particular area of the

body. On the left is the facial atrophy seen in patients on anti-

viral therapy in HIV infection. On the right is a specific

lipoatrophy surrounding an insulin injection sight for diabetes.

A 2013 study sought to determine why the opposite things happen with fat in different places. They tracked different markers in each location and found that mitochondrial changes were the same in visceral adipose tissue (VAT) and subdermal adipose tissue (SAT). But the signals to build fat decreased only in SAT. Most telling, inflammatory signals were much greater in SAT than in VAT; it may be that less inflammation leads to less fat wasting. Strange that fat would be linked to inflammation – or maybe not - keep reading.

Fat may be considered evil, but it serves a purpose. The problems that lipodystrophy patients encounter underline that fat is a necessary tissue for animals. Problems arise when you accumulate too much of it, either under your skin, around your organs, or in your blood. If you don’t use the calories you take in for energy, your body will store them for later.

Chemically, a fat is made up of three fatty acids (see below) attached to a 3-carbon glycerol molecule. In adipose tissue (from latin aipem = fat) and subcutaneous fat, these triglycerides, also called triacylglycerols (tri = 3, glycer = glycerol, and acyl = acid) are stored until they are released to the blood stream as fatty acids alone. The fatty acids can then be broken down and used to generate ATP in the cells.

Fats are a much more efficient storage form of energy as compared to glucose or glycogen. There is 4.5 x more energy in fat as compared to the same mass of glycogen or glucose. In addition, since fats are hydrophobic (hydro = water, and phobic = fearing), they can be stored without water. These two factors mean that a lot of energy can be stored in a little space.

A fat molecule is really a triglyceride. The right structure is a

typical triglyceride with three fatty acids in black connected

to the bluish glycerol. By ester bonds in dark red. A trans

double bond is shown in green. On the right is the partial

hydrogenation process that converts a polyunsaturated fat

into a trans fat. Usually there is a mix of products, with some

cis bonds being converted to trans bonds.

Glucose first gets stored as glycogen, but we make only a certain amount of glycogen. Usually a human has about one lazy day’s worth of glycogen. Energy beyond that gets stored as fat, and that’s a good thing. Imagine how large we would all be if we all our energy reserves were in the form of glycogen + water. A normal human adult male would weigh an extra 110 pounds (50 kg)!

A fatty acid is a chain of carbons with a carboxyl group (HO-C=O) on one end. If the chain of carbons contains only single bonds, then the fatty acid is called saturated. If there is one double bond between carbons, then it is an unsaturated fatty acid, and if there are two or more double bonds (unsaturations), then it is a polyunsaturated fatty acid.

The same terminology is used for triglycerides (fats) made from the fatty acids. A fat with only saturated fatty acids is a saturated fat. The double bond type also makes a difference for the fatty acid and fat. If the bond is in one configuration, it is called cis, and it creates a bend in the chain. If the double bond is in the other configuration, then it is called trans, and it is much straighter, like a saturated fatty acid.

You have heard of the benefits of polyunsaturated fats as opposed to saturated fats, and of the evils of trans-fats. Saturated fats tend to produce bad results in the blood stream. Their breakdown results in more acetates which stimulate cholesterol production. Also, saturated fats tend to clump together and form blockages in vessels. This leads to atherosclerosis and can kill you.

The left cartoon shows the buildup of plaque over time in

atherosclerosis. It takes along time, but we all seem to be

working hard to make it happen. The right image is a

photomicrograph showing the blockage in a large coronary

artery. Think the amount of blood getting through is enough

to nourish your heart? Think it’s going to have a happy ending?

However, saturated fats are good at promoting liver and lung health, so some saturated fat in your diet is not a bad thing. Trans-fats, on the other hand, are harder to discuss. They can be made in a factory by removing some double bonds from polyunsaturated fats by partial hydrogenation. They also occur naturally, but are very rare compared to cis fats, so they don’t usually cause a problem.

The vast majority of trans fats we eat are industrially made. The trans double bonds are created in the hydrogenation process (adding hydrogens to reduce the number of double bonds). Some cis- double bonds become trans- double bonds during the process.

Industry likes the saturated and trans-fats because they tend to be more solid at room temperature (higher melting temperatures). Saturated and trans-fats have more hydrogens (see picture above). The kink in trans-fats also increases the melting temperature.

The hydrogens and kinks lead to more interactions between the different molecules – they hold on to one another more tightly. Melting is basically making the different molecules separate by adding energy, so the added hydrogens have the end result of raising the melting temperature. This is good for making things like margarine.

Unfortunately, trans-fats tend to increase low-density lipoprotein (LDL) production; these contribute greatly to artery clogging and heart disease. The blocking of arteries is bad enough, but if they occur in the brain, or if part of a plaque breaks off, travels to the brain and blocks a vessel – that’s a stroke. There’s not much that’s worse than a stroke.

Saturated fats also raise the levels of LDL’s - so why are trans-fats worse for you than saturated fats? The levels of LDLs are only one aspect in disease promotion, the level of the good-for-you HDLs (high density lipoproteins) is just as important. It's the ratio of LDL:HDL that matters.

In the space of the vessel are some large cells with very

light cytoplasm that looks like Swiss cheese. There are

many small clear droplets and some larger ones. These

are fat droplets and give the cells their name – foam cells.

You can see that some have more than one nucleus. Two

diseased macrophages will often merge into

multinucleate giant cells.

When you eat saturated fats, both the LDL and the HDL levels increase, so the ratio stays generally the same. With trans-fats, the LDL production goes up but the HDL level stays the same or decreases. This leads to a bad ratio and disease progression.

The next question then is how do HDLs help prevent disease caused by LDLs? LDLs supply cholesterol to the cells that need it – and that’s all your cells (more on this next week). But if there is too much LDL, then they start to accumulate in the vessels and can form things like foam cells.

Foam cells are tissue macrophages located in/on the vessel walls. The job of macrophages is to eat things, so these macrophages eat up the extra LDLs in the area - but they don’t break them down. They build up and start to look like foam inside the cell. Unfortunately, the macrophages then become part of the problem; as they accumulate they form fat streaks in the vessel wall. This is the beginning of plaque formation and atherosclerosis.

A 2005 review looked at how HDLs are health promoting. It turns out that they steal cholesterol from LDLs, but they don’t promote the formation of foam cells and plaques because of their different structure. Therefore, having more HDLs will rescue more cholesterol from LDLs and transport it to the liver for eventual destruction.

The top cartoon shows how HDL help get rid cholesterol

after it has been phagocytosed by a macrophage foam cell.

A pre-HDL interacts with receptors on the macrophage

which then transfer cholesterol to the HDL. This is taken to

the liver where it is broken down and reused for bile

production. This is called reverse cholesterol transport. The

bottom image shows the functions of HDL, even beyond its

ability to negate the unhealthy effects of LDLs.

By stealing the cholesterol from LDL, HDLs also stop many mechanisms that can lead to vessel blocking, like the stimulation of vessel inflammation by LDLs, the formation of clots in the vessels (HDLs are anti-thrombotic, a thrombus is a clot), and by preventing the oxidation of LDLs.

Oxidation of LDLs leads to oxygen radicals can damage vessel cells and promote plaque formation. But HDL complexes include an enzyme called paraoxonase, which prevents the oxidation of closely associated LDL molecules. Preventing oxidation also reduced the production of pro-inflammatory molecules in the vessel wall and decreased the recruitment of some inflammatory cell to the area. Hurrah for HDL!

But wait – of course there’s an exception. HDLs from patients with existing diseases, like coronary artery disease (CAD) or chronic kidney dysfunction (CKD) actually contribute to plaque formation rather than prevent it! A 2013 review talked about how HDLs from CAD patients limit the anti-inflammatory and repair processes in the vessels cells, and in CKD patients promote inflammation and raise blood pressure. I guess the best way to prevent atherosclerosis is to not develop atherosclerosis.

Overall, you want to reduce fat intake, but especially trans-fats and saturated fats. Food labels are now required to show how much trans fat is in the product, but the manufacturers are getting around the regulation. They combine different fatty acids in a fat and they call them interestrified fats. Partial hydrogenation is still a major factor, but they aren’t called trans-fats. This allows them to keep it below the FDA radar. Interesterified fats don’t exist in nature – that should tell us all we need to know.

What we need is a way to partially hydrogenate the polyunsaturated fats that does not create trans-fats – you work on that while I butter my bagel. Next week we can look at more aspects of fats, and how they are different from the other lipids.

Gallego-Escuredo JM, Villarroya J, Domingo P, Targarona EM, Alegre M, Domingo JC, Villarroya F, & Giralt M (2013). Differentially Altered Molecular Signature of Visceral Adipose Tissue in HIV-1-Associated Lipodystrophy. Journal of acquired immune deficiency syndromes (1999), 64 (2), 142-8 PMID: 23714743

Xu S, Liu Z, & Liu P (2013). HDL cholesterol in cardiovascular diseases: The good, the bad, and the ugly? International journal of cardiology, 168 (4), 3157-9 PMID: 23962777

Barter, P. (2005). The role of HDL-cholesterol in preventing atherosclerotic disease. , 7(Suppl F), F4-F8. European heart Journal, 7 DOI: 10.1093/eurheartj/sui036

For more information or classroom activities, see:

Trans fats –

http://www.mayoclinic.com/health/trans-fat/CL00032

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CCoQFjAA&url=http%3A%2F%2Fwww.bellinstitute.com%2FDisplayResource.aspx%3FID%3D466&ei=b2hoUoDRJOb4yQGupIHAAg&usg=AFQjCNGD6kQGhpmZww0_ozraek5mgGPkVw&sig2=q8qehRUhNomxEp73WrI0DA&bvm=bv.55123115,d.eW0

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&ved=0CDAQFjAB&url=http%3A%2F%2Fnfsmi-web01.nfsmi.olemiss.edu%2FDocumentDownload.aspx%3Fid%3D2494&ei=b2hoUoDRJOb4yQGupIHAAg&usg=AFQjCNFOoBeS_l85BN1JdxRW44Oeq7_YUA&sig2=1drqYVxeKTILlnhbtU-jrw&bvm=bv.55123115,d.eW0

http://www.pbs.org/wgbh/nova/education/activities/3401_01_nsn.html

http://www.uen.org/Lessonplan/preview.cgi?LPid=1265

http://www.bantransfats.com/mcdonalds.html

http://howtosmile.org/record/4406

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=17&ved=0CFIQFjAGOAo&url=http%3A%2F%2Fllaa.org%2Fsites%2Fdefault%2Ffiles%2FTrans%2520Fat%2520Activity%2520Outline.pdf&ei=KWloUvTMK8TgyQH__oDQAw&usg=AFQjCNGmgcQon8-2bYF5FRmIo5V9_4nrtg&sig2=moOFRCVVJHrdsX_RxIx2BA&bvm=bv.55123115,d.eW0

http://www.slideshare.net/muskokee/transfats-biology-of-food-safety-class

interesterification –