Archive for the ‘biochemistry’ Category

A friend and I met for an afternoon chat; we saw one another in the parking lot and together headed toward our destination. We talked as we walked, slowly tracing our way to the awaiting patio. At some point along our journey, we simultaneously noticed that we had begun to drift apart. We exchanged a look and each of us gazed down, both wondering what had caused us to subconsciously choose different paths. Interestingly, she had unwittingly followed a curvy sidewalk carved into the landscaped lawn. I, on the other hand, had continued to march straight toward the destination, inadvertently pursuing the shortest distance between two points.

We giggled, as girls do, sparking a lively discussion regarding our innate differences – which, of course, resulted in an appreciation of our overall similarities. I realized the acquaintances who become my close friends mimic the phenomenon we experienced while walking: They are the people who confidently and independently follow their own path, yet arrive at the same destination. (I’m certain there’s an Ayn Rand quote in here somewhere.)

We do what we do. And we do what we want. (Caveat: What some people want is to do what they think others want them to do, or expect them to do.) But why is this? Are mere chemicals responsible for free will? What pathways give us individuality, from whence stems innate motivation (or lack thereof); can a change in chemicals change innate responses? Are our subconscious decisions predetermined? Are they dynamic in space, time, and circumstance? Can we purposely choose against them? Are we able to permanently alter our seemingly inherent characteristics?

I could go on and on with these questions; unfortunately, not I nor anyone else really has an answer. We have many clues, glimpses, hopes; but alas, nothing concrete, nothing that holds true uniformly or ubiquitously for the entire human population. Interestingly, while there are many drugs that affect personality, decision-making, and preference, these compounds are often among the least understood; in fact, the mechanisms of action for entire classes of mood-altering substances remain wholly elusive. Doctors prescribe anti-depressants based solely upon the appearance of effectiveness, with no understanding whatsoever of how or why they work. There do seem to be some consistent biochemical messengers that pop up again and again in studies of personality, attitude, choice, inclination, and other cognitive-based traits; these compounds are inevitably influenced by the drugs we find effective at eliciting responses in these areas (though, oddly, often we only notice this ex post facto).

I’m enthralled by these compounds. Not only are their direct effects (those we’ve discovered so far, anyway) amazing, but there seems no bodily pathway immune from some indirect effect of their action. They serve as a dynamic reminder that our bodies run not on a series of one-way linear biochemical reactions, but that we function as a network of interconnected, amenable reactions – and because the whole is greater than the sum of its parts, even the most innocuous compounds are vital to our optimal functioning.

Monoamine neurotransmitters appear to play an important role in linking our conscious behaviors with our subconscious existence. These include the lately in vogue compounds serotonin, dopamine, norepinephrine, and their relatives. Just knowing which compounds are involved seems only the tip of the iceberg, however: Not only does the manufacture, quantity, location, and concentration of the chemical in question matter, but so does the characteristics of the corresponding receptor proteins as well as their ratios and interactions with seemingly unrelated pathways along the route. It seems that dopamine, in particular, has a functional role in our decision-making processes, all of which probably have a subconscious component.

Do yourself a google for the hypothalamic–pituitary–adrenal (HPA) axis and read all about how our major body systems are intertwined and interdependent. I especially enjoy learning about how my gut has a mind of its own – complete with literal mood swings and impressionable responses to my bodily conditions and those substances I choose to expose my innards to.

Fascinatingly, these compounds that make us individuals also seem to play a role in social interactions and cohesion. I am currently reading The Wisdom of Crowds, given to me by a former student (and ongoing friend); I cannot help but suspect maybe culture is actually the average of our individuality, beautiful and wondrous exactly by its projection of the best of our collective biochemical tendencies, exactly capturing the perfection of our imperfections.

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The Secret Recipe

Posted: February 26, 2011 in biochemistry, evolution, genetics

I am guilty, along with countless texts, websites, experts, and novices, of an academic travesty – using an inaccurate simile to explain scientific phenomena. Namely, the description of genomic information as a blueprint and the body as the resultant structure.

Thank goodness I recently failed to notice The Agile Gene was merely a renaming of Nature Via Nurture, and was therefore conned into reading it again. It reminded me of what I already knew, but lie buried beneath the weight of my formal education… Our DNA is not a blueprint but a recipe. We are not built, but baked.

The building designed from a blueprint is literally the sum of its parts. A cake, however, or a human, is a whole greater than its sum; it takes on properties not obvious from the list of ingredients. What, asks Blumberg in Body Heat, is the essence of a chocolate cake? Is it the eggs? Flour? Cocoa? No, these are merely ingredients. Nor is it the pan, oven, or whisk. A recipe is clearly not a cake, either. What is the essence of a human? How can it be captured?

The reality is that simply unraveling our DNA does not explain how it works, any more than knowing the alphabet helps you to read a book (with apologizes to Charles Arthur).

It seems we expect too much of our limited understanding of DNA, which derives from the metaphors we use about it. When we can only describe something indirectly, it may falsely acquire the expectations realistic of the associated analogy. We therefore look to genes to solve riddles, fix problems, and explain mysteries. However, we forget that it just isn’t so simple…

Consider what the greatly missed writer Douglas Adams pointed out – Imagine that you were trying to describe how to make a fruit cake by writing the blueprint: currant here, surrounded by certain amount of air-filled cake mixture, and then more currants. It would be hellish. So how do we make fruit cakes? Not by blueprint. We use recipes – mix these things together, bake at a particular temperature for so long, and voila: if you’ve got the components right, you’ll have currants distributed satisfactorily around your finished product.

Think about it: Bakers use, by and large, the same ingredients in many recipes to produce a wide variety of unique confections. The art of baking lies in the ratio of flour to sugar to eggs to salt, and such; not in using different ingredients for each different recipe. Can you predict the precise structure, placement of parts, consistency, etc. of the product just by looking at a recipe? Nope.

Likewise, many organisms share many genes, probably from a common ancestor. We change around the timing, intensity, and location of gene expression, throw in a few special touches, and viola! become unique individuals. But it isn’t just genes that make us who we are – environment clearly affects the expression of genes.

Okay, so you’ve made the cake batter or bread dough or what have you – now what? The oven condition and quality, local elevation, humidity, etc. all have significant impacts on the final product. Some cooks create masterpieces at low temperatures for a long time; others dazzle with short durations of high heat.

The secret ingredient we’re often missing when we describe our genes as a blueprint is quite possibly that elusive fourth dimension, forgotten usually by its continuous presence – time. You can break a structure back down into its constituent components; you cannot unbake a cake. Or a person.

One of my favorite analogies used by Ridley is: You and I and other animals share the genes necessary to make vertebrae. This neck sauce, as he calls it, is used to marinate giraffes for a much longer time during their development than us people; yet we too were briefly soaked in that sauce. Snakes are basted in the marinade during their entire development and thus end up with a neck the length of their body! But each of us express the same neck genes in our neck region; the difference is how long, and how much marinade we soaked in as we developed. You see, we were not assembled, we were concocted.

If something disrupts our proper development, or throws off the timing of gene expression, then that something has the potential to cause disorders and disabilities. We are the products of the conditions in which our genes are expressed; not only that, but the conditions we find ourselves in further influence future directions of gene expression.

As the psychologist Gary Marcus has pointed out in yet another attempt at an applicable analogy by which to understand something not quite understandable, genes function like IF-THEN lines of code in a computer program. The IF refers to the regulatory portion of the gene and THEN refers to the protein template region.

One Gene = One Protein

Posted: February 12, 2011 in biochemistry, genetics

Once upon a time, every organism was a single cell. Whether the product of binary fission, mitosis, or sexual fertilization, all of life’s secrets are held in a microscopic unit with an average (eukaryotic) diameter of 0.00001 meters.

What the components of any given cell are, whether it contains organelles, and which, and a number of other variables are dynamic between creatures and over time. The one thing all cells have, however, that defines them as living organisms, is heritable information – nucleic acids – and the machinery required to process those directions – ribosomes.

When our DNA directs growth and development, and provides the defining characteristics of our selves, what really is happening? How can a four-letter sequence of sugar-phosphate-nitrogenous bases create a living being? And then, in the case of multicellular organisms, build it up to a coordinated, functioning whole?

Excepting our red blood cells, all our somatic (body) cells contain our entire genome. The only difference between cells in different parts of your body is WHICH genes are turned on, to what degree (level) each is expressed, and when. In addition, the genes you turn on and off even within distinct body regions are dynamic over time – coordinating the correct set of genes is essential for proper development, proportional body growth, to maintain homeostasis in an ever-changing environment, and to regulate life cycles.

What does it mean to say that a gene is expressed? Less than 2% of our entire genome actually consists of “genes” – these are the stretches of nucleic acid “words” that encode instructions for the creation of a specific protein. Proteins themselves are composed of amino acids – your DNA is read as three-letter words; each triplet of bases, termed a codon, specifies one particular amino acid equivalent. If you had a random collection of objects from which to choose, you might say “hat” – and could then also select the literal item itself. You could then perhaps say “bat,” and so on. Your DNA gene would be the complete list of three-letter codon words like “hat”  and “bat,” and the piece of the protein it referred to (individual amino acids) would be the objects we named a hat and bat and etcetera. A gene, then, is a stretch of DNA that refers to an actual object; genes are said to be expressed when that gene is read as directions and the object, a protein, is assembled within your cells. When all these components have been properly created and distributed, you might have a full game of baseball, or a functional organism.

To protect that most precious of all molecules, DNA, your cells enclose it in a membrane-bound nucleus. When a particular gene needs to be expressed, that specific DNA region is copied into an RNA transcript. This RNA copy of the DNA gene is then exported from the nucleus to the cytoplasm, where expression is completed. The process of creating an RNA copy of a single gene from the DNA template is called transcription; just as the general definition of the term would imply, this process involves making a same-language copy of the DNA words. The alphabet looks nearly the same (the letters are G, C, A, and U – where U is substituted for the T of DNA); you can think of RNA as a different dialect, or accent, of the language of DNA.

The RNA transcript of a demanded gene is now greatly shorter, and therefore easier to work with, than the original full DNA genome. This sequence may be further processed before the act of translation occurs in the cytoplasm. During translation, the RNA triplet codons of nucleic acids are exchanged for the associated amino acid in a growing peptide chain. In other words, just as with the general definition of “translation,” one language is changed into another – but while retaining the original meaning. As the polypeptide grows, it is folded and processed and eventually emerges as a functional protein. At this point, your original DNA gene has been expressed.

All of your characteristics are the result of protein creation during gene expression. Your eye color is the accumulation of proteins that reflect certain wavelengths of light back to the eyes of others (if you have green eyes, or brown eyes, or hazel eyes, it’s because the protein pigmentation in your eyes does NOT absorb that particular color and shade, reflecting it for others to see). Likewise for your hair color and skin color, and all color! All of these phenotypic traits are coded for by not one, but a complex combination of genes. Not only do individual genes and proteins make you who you are, but the interactions between multiple genes and proteins also contributes to your unique self.

“There is grandeur in this view of life, with its several powers, having been originally breathed by The Creator into a few forms or into one; and that, whilst this planet has gone cycling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved.”

(Last paragraph from Darwin’s The Origin of Species)

Incidentally, ladies and gentlemen, today, 12 February is International Darwin Day.

Photo 51

Posted: February 12, 2011 in biochemistry, genetics

How does DNA work? How can something so seemingly arbitrary – something composed of four bases each containing simply a sugar, a phosphate group, and a nitrogen-containing compound – determine our appearance, instincts, thoughts, behaviors, and very existence?

Humans have 46 chromosomes, or 23 paired sets (one each from ma and from pa!). Altogether, the human genome has roughly 3 billion base pairs – in other words, the genetic information directing our lives is a “book” containing 3 billion “letters.” If you were to stretch it all out end-to-end, you would discover yourself to be carrying about 6 feet of DNA per cell, or 2 billion miles of genetic information total. Wow! The alphabet itself contains only four letters; most of the words are the same for each of us (think: if they weren’t, you might have limbs or organs in different places than the guy next to you!), but the difference between any two humans can reach up to 0.1% (this may seem like a small number, but it is still about 3 million letters). Most of the differences, called single nucleotide polymorphisms, are singular and located in isolated spots rather than in full “words” or long stretches.

Journey Into DNA

Humans have an estimated 20,000-25,000 genes. These “words” – the part of your DNA that is coded into protein – make up only about 1.5% of your total genome! What does the rest do? Well, that question is a work still in progress: http://www.genome.gov/

How do we know what DNA looks like? How do we explore our genes at the molecular level? In biochemistry, form and function go together like peanut butter and bananas (trust me, it’s good). Most of our knowledge comes from analyzing data garnered during elegantly designed, indirect experiments. Today, we often use highly sophisticated computer programs to discern the secrets of our genes, but originally we relied heavily on X-ray diffraction.

From this image, taken by Rosalind Franklin in 1952, did modern genomics emerge:

The Anatomy of Photo 51

Hydrophobia

Posted: February 9, 2011 in biochemistry, chemistry

Fat is all the rage: From dissing trans to flaunting omega-3s, everyone who is anyone is talking about it. But what has made fat so phat?

Lipids are composed of hydrocarbons and are insoluble (or have limited solubility) in water. This category of organic molecule includes a relatively diverse range of compounds, including waxes, terpenes, steroids, oils, and, yes, those things we call fats. In addition, “fat-soluble” vitamins (A, D, E, and K) are themselves lipids. This is why you are told to add fat to your salad – since they won’t dissolve in water you don’t get these nutrients unless you emulsify them!

A primary role for lipids is maintaining a barrier between the hydrophilic and homeostatic internal cell environment and dynamic external conditions. Phospholipids play the role of protective barrier, forming that selectively, semi-permeable plasma membrane around our cells. Cholesterol is a lipid steroid that is a CRUCIAL cell membrane component, buffering us against temperature and providing other unique functions. We’ll talk more about that later.

In addition to being major cell membrane components, lipids are essential for cellular signaling (e.g. hormones), immune function, and serve as our long-term energy storage molecules (you already know this, though probably in less-politically-correct terminology…). Fat is more efficient than other macromolecules at storing potential energy (as trapped in the chemical bonds), holding 9 kcal of chemical potential energy per gram.

Fats and oils are composed of the three-carbon alcohol glycerol attached to one, two, or three fatty acid chains. When all three of the glycerol carbons are condensed with a fatty acid “tail,” we know the resulting molecule as a triglyceride.

Hydrocarbon chains can be saturated or unsaturated. Saturation just means that all the carbon atoms have four (their maximum!) single bonds, while the degree of unsaturation corresponds to the number of double bonds introduced between carbon atoms. Since the general definition of “saturation” implies being filled or full, it makes sense to conceptualize that the chemical bonding capacity is fully utilized in saturated compounds.

Notice how the double bonds produce “kinks” in the chain? As it turns out, the level of unsaturation corresponds to the fluidity of the fat. That’s why saturated fats are solid at room temperature, while polyunsaturated fats tend to be fluid. “Trans” fats are artificially (usually) produced double bonds (“hydrogenation” is the chemical process of introducing trans-double bonds to a fatty acid chain – watch out for this sneaky label terminology); however, they fail to produce the characteristic kinks in fatty acid chains. The maintenance of a rigid (straight) structure allows for a more solid form and gives us margarine and shortening. However, your body isn’t fooled by this fake stuff and we now know it was a really, really bad idea…

What else is a bad idea? Taking anabolic steroids. Well, okay, that is purely opinion and doesn’t always hold true but you see my point. Which is to transition into talk about the steroid class of lipids. All steroid compounds have a characteristic carbon backbone of a fused, four-ring structure on which various functional groups are attached.

Cholesterol, a good guy, is synthesized by our bodies (no dietary input needed!) and, in addition to serving as a crucial membrane component, also serves as a precursor to sex hormones and Vitamin D (a conversion pathway activated by unfiltered sunlight!). The way your body transports insoluble things like cholesterol from cell to cell, through your bloodstream for instance, is by packing them up inside spherical carrier molecules…

Lipoproteins are globs of protein and lipids all intertwined. These are categorized according to density. Since fat is less dense than protein (think: fat floats, meat sinks), lower density lipoproteins are those that have a relatively high proportion of fat to protein. On the other hand, higher density lipoproteins have a higher ratio of protein to fat. But wait a second! Do those terms sound vaguely familiar? I hope so! Low-density lipoprotein and high-density lipoprotein are also know as LDL and HDL, respectively. Cholesterol is cholesterol; but to be healthy we need protein-packed HDL delivering it to all the right places. LDL is not so efficient at distribution, and also tends to accumulate in the body’s passageways.

Okay now to the really hot topic. The term omega, as it relates to fatty acids, refers to the terminal carbon atom farthest from the functional acidic (carboxyl) group. In other words, polyunsaturated fatty acids have two distinctive “sides,” or endings. On one side is an acidic carboxyl group (let’s call this the “alpha” end), while on the other side lies an “omega” end. The number associated with a type of fat defines the position of the first double bond (unsaturation) relative to the omega end. For example, omega-6 fatty acids have a double bond on the sixth carbon atom from the omega side.

There are three major classes of omega fats that are important in our diet. These are omega-3s, omega-6s, and omega-9s. All three serve functional physiological roles, and it seems fairly meaningless to discuss the requirements for each individually. What seems relevant and important to our health is the RATIO of each in our bodies. It appears optimal to have relatively high levels of omega-3s, medium levels of omega-6s, and low levels of omega-9s. However, the American diet has become heavy in omega-9s (largely from animal and processed sources), overly high in omega-6s (found in many plant-based oils, as for fried foods), and dangerously sparse in omega-3s (you know, seafood and such). Clinical studies suggest that altering our ratio of intake, rather than focusing on an individual fat type, is the most effective way to create positive biochemical changes in our bodies.

A review of recent research discloses mounting evidence that disturbances in fatty acid metabolism may link chronic psychological stress, endocrine responsiveness, and psychopathology. In particular, relatively lower omega-3 status corresponds to negative outcomes in physiological stress response. Research also suggests that the compositional changes made by our bodies to specific fatty acids may be able to serve as markers for stress and indicators for disease in the future (Laugero et al. 2011).

Click here and click here for fantastic sites to use while studying lipids!

Carb Overload

Posted: February 6, 2011 in biochemistry, chemistry

Ahhhh carbs. We all love them, we all love to hate them.

But what is it about a freshly boiled bagel, a pile of spaghetti, or a blueberry muffin that tempts us so? Well, that’s another discussion for another post. Namely, hormones. Which is two other posts, actually – lipids and polypeptides (protein).

For now, let’s try to understand the nature of the beast. What exactly is a carbohydrate? Are all carbs created equal? What’s the difference between “simple” and “complex” – and should I care?

Saccharides, generically called carbohydrates, are one of the four major categories of macromolecules – remember, this means that they have a carbon backbone with a characteristic functional group attached; additionally, they are polymerized into larger (more complex) molecules via dehydration (condensation) synthesis reactions and broken down in your cells using hydrolysis.

The monomers of carbohydrates, called monosaccharides, all have the same basic empirical formula: Cm(H2O)n. What this means is that the associated functional group is actually two hydrogens and an oxygen atom. For our purposes, remember this: The basic formula for a sugar is some multiple of (CH2O). For example, glucose has the chemical formula C6H12O6 – which is the basic sugar code times six. –Click here, click here!! JMol Glucose

Sugars and their polymers (polysaccharides) are the products of photosynthesis – these compounds are created to store the radiation energy from sunlight in tangible form. During that conversion process, energy becomes trapped in the chemical bonds holding together each atom in the sugar molecule. This potential energy can then be stored for later use, or be consumed by a secondary organism (such as us!).

Monosaccharides, or simple sugars, can be condensed together to form polysaccharide chains, becoming more complex(!) as they get longer and branch into bulkier forms. The more complex they become, the more potential energy they store in all those new chemical bonds. In plants, shorter saccharides, such as natural fructose, give sweetness and quick energy when we consume them, such as in fruit. Longer saccharide chains, such as starches, can take our bodies much longer to break down. Some sugar compounds are so complex that our bodies are incapable of breaking them down into the constituent sugar monomers (subunits); we generally call things in this class “fiber” – it passes pretty much right through us without being utilized for fuel. Even if we could process these compounds, our body makes the economical decision that it would cost more energy than we would gain.

Unlike plants, you and I do not store excess carbohydrates in our body. When we consume sugar polymers, we use them right away for short-term fuel supplies. A relatively small, finite amount more is stored as glycogen in liver and muscle tissue.

This is utilized in maintaining stable blood glucose levels and is available during the epinephrine (adrenaline) -induced “flight-or-fight”  response, and is what you are replenishing when you eat 30-90 minutes after a tough workout. Aside from building new muscle mass, however, there is no way to make your body store extra glycogen. Beyond this small reserve, any surplus sugars we consume are converted for storage into – you guessed it! – fatty acids. Lipids are our bodies’ preferred form of long-term potential energy storage molecules.

When you’re reading those ingredient lists, look for anything ending in “-ose” – this is the sugar suffix in chemical nomenclature, used to designate compounds your body utilizes as a short-term fuel supply.