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Principles of Physiology (BIOL 3103)

CHAPTER 2: BIOMOLECULES
OK, so were in chapter 2 now. I should probably have addressed this question by now: WHAT IS PHYSIOLOGY?
There are a lot of definintions out there for physiology: Maintainance of an internal steady state, is a popular one. Or if you want a to define
it in terms of academic disciplines, theres the branch of biology that deals with the functions and processes of living organisms. But I have
a simple one for you:
PHYSIOLOGY IS LIFE!
Maybe thats too simple because you can still simulate physiological processes in non-living systems. But I would argue that without physiology there is no life and that physiology is the essence of all living things.
As we will see in this chapter, every complex molecule on the planet is prone to breaking down into simpler stuff. Organisms are composed
of gazillions of complex molecules1. If you want a more robust definition of physiology, you could say that physiology is all about balancing
out the synthesis and decomposition of the gazillion molecules that make up all organisms. Physiology converts energy to order. It is the
anti-chaos.
Before I get too carried away here, let me emphasize that physiology is not magic. Although there is much we still do not understand, thus
far, all of the principles that underly the physiological processes we know about are derived from basic physical phenomena. Opposite
charges attract. Molecules diffuse from areas of high concentration to low concentration. Energy can be stored in and released from chemical bonds. Physiology is not a spark initiated in an otherwise inanimate lump of tissue. It is a more or less continuous set of phenomena
that often carry on even after an organism has died.
As for the gazillions of molecules mentioned abovethe ones that make up living organismsmany of them are biomolecules. They are the
subject of this chapter.
By the way, were going to talk about chemistry here. You know chemistry, right? No? Then youd better check out the link to the right2 and
do a quick refresher.
Back already? OK, here we go with Biomolecules. There are 92 naturally occurring elements on earth, of those, 25 are essential for
life3. These elements come together to form the four building blocks of life, carbohydrates, lipids, proteins, and nucleic acids. These types
of macromolecules all originate from some sort of biological synthesis, so you either make them or eat them. Each macromolecule is a large
unit composed of smaller units known as polymers; and polymers are composed of even smaller units known as monomers 4.
Lets go over each of the four types of biomolecules one-by-one, carbohydrates first!

Carbohydrates
In the simplest terms, carbohydrates are known as saccharides, or sugars. They are composed of carbon, hydrogen, and oxygen, typically
with a 1:2:1 ratio, and they exist in three different structural formations, monosaccharides, disaccharides, and polysaccharides. Monosaccharides, or simple sugars, contain a single sugar molecule and are the basic energy sources for cells; examples include glucose 5 and fructose 6. When two monosaccharides are bound together by dehydration synthesis (they bond together and give up a water molecule),
to form a disaccharide. Examples include maltose, lactose, and sucrose.

The most complex type of carbohydrate is the polysaccharide.

Polysaccharides are composed of three or more repeating monosaccharides and include molecules such as starch, cellulose, and glycogen
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.
So we all know that carbs are an energy source. But thats not all theyre used for. Carbohydrates can make up the structural framework
of a cell, and they also play an important role in cell-to-cell signaling and identification.
Cellulose, the most abundant organic molecule on earth, is an example of a structural carbohydrate. Due to its tightly bundled glucose molecules, cellulose is very stable and rigid8. In case you havent figured it out, were talking about wood, paper, hayjust about any kind of stiff
plant material. People cannot normally digest cellulose, but it is good to have it in your diet nonetheless. Animals that do digest cellulose
(cows, horses, deer etc) do so with the aid of special bacteria in their guts.
Chitin is another example of a structural carbohydrate. It is also hard and rigid and is a primary component of arthropod exoskeletons 9.

One of the most important roles carbohydrates play in the human body is signaling. Glycoproteins and glycolipids are the most common
signaling carbohydrates. Glycoprotein molecules 10 are an amalgamation of proteins (well get to those in a minute) and oligosaccharides
(i.e., small polymer composed of three to nine glucose molecules). The protein parts are often embedded in cell membranes so that the carbohydrate tail sticks out.

The carbohydrate tails of these glycoproteins play important roles in cell-cell interactions and are involved in the immune response. In
fact, antibodies11, one of the key products of the acquired immune system, are glycoproteins. Most antibodies had two arms with glycans12
at each end that enable the antibody to attach to very specific things, like bacteria or virus infected cell.
There are also structural glycoproteins that occur in the connective tissues of many organisms. They help bind together cells, and fibers.
Some cells have so many glycoproteins and glycolipds on their surfaces that there is essential a coat of sugar or glycocalyx13. Next time
you want to say something nice to your significant other you can say he or she is a sweet as a glycocaylx. The glycocalyx helps cells distinguish between self and non-self, and it helps with identification of diseased cells.

The fuzzy stuff on the perimeter of this cell is the glycocalyx

Lipids
Lipids hate water. They are all hydrophobic, or water fearing molecules with lots of non-polar carbon-hydrogen bonds and a carbon backbone. Its those non-polar bonds that make lipids hydrophobic-theres nothing there to interact with the slightly polar water molecules, so
lipids tend to remain separate from water. And thats often a good thing. Our cell membranes (which are mostly lipids maintain themselves
thanks to the hydrophilic nature of lipids. Lipids do a lot of things besides making membranes. They are used for energy storage (fats are
lipids), structural support, and cell signaling (lots of hormones are lipids).
For most people, lipids are associated with fatas in the energy storage substance in our bodies that has given rise to a huge weight-loss industry. This sort of fat, when stored as energy reserves, consists of tryglycerides. Tryglycerides are large molecules composed of three fatty acids bound together by a glycerol backbone.

The fatty acid chains in a triglyceride are long strings of non-polar, hydrophobic hydrocarbons. These chains may be saturated (i.e. they
have all the hydrogen atoms they can hold) or unsaturated with one or more double bonds among the carbon molecules.

The amount of saturated fatty acid chains affect the chemical and physical properties of a fat. For example, saturated fats have a higher
melting temperature than unsaturated fatty acids, and remain solid at room temperature (crisco and lard contain saturated fat).
photo of some lard

Block of lard

Aside from culinary preferences, saturated vs. unsaturated fats can be important physiologically. Think about what might happen to a fish
or other ectothermic14 animal that lives in a very cold environment if it had lots of saturated fat.
To get energy from fat, the triglyceride must first be separated into its fatty acid chains and glycerol backbone. Then a process called beta
oxidation takes the fatty acid chain apart two carbon molecules at a time. The energy in the carbon-carbon bonds is then harvested to generate Adenosine Triphosphate (a nucleotidediscussed below), which is the primary energy currency in almost all cells.
Phospholipids play an important role in the structural integrity of cell membranes. Phospholipids are composed of two regions, a hydrophobic tail and a hydrophilic head. The hydrophilic heads are attracted to water whereas the hydrophobic tails repel the water. This
propensity for repelling water, while attached to a hydrophilic head, forces the tails to aggregate, creating a bi-layer of hydrophilic tails
on the interior and hydrophobic heads on the exterior 15. This bi-layer forms the membranes, or barriers, seen in all cells.

Fluid Mosaic Model of the Cell Membrane

Phospholipids are also functionally important, carrying out processes such as the isolation of potentially harmful materials, holding water
in plant cells, and removal of unwanted waste. The functionality of each vacuole is dependent upon the cell type and are more prominent in
plant and fungal cells than animal cells.
Phospholipids are found in two forms, phosphoglycerides and sphingolipids 16.

Phospholipids and sphingolipids are both components of cell membranes, although phospholipids are much more common. The role of
sphingolipids is not really known but they may provide more stability to the outer leaf of some membranes. They may also help to form
lipid rafts17, or patches of membrane material that maintain their integrity among the more fluid phospholipids surrounding them. These
rafts often carry sets of special membrane proteins (well get to those, I promise) that work together in series to perform a particular function. By keeping these proteins together, lipid rafts help compartmentalize cell functions.
Another important class of lipids are steroids. Steriods are derived from cholesterol.

For most people, steroids connote performance-enhancing drugs and sports scandals. Thats because steroids are often employed as hormones. Hormones are chemical messengers that are carried in the blood as a means of broadcasting information to lots of different tissues.
Name a few hormones off the top of your head, and you are probably talking about steroids. Estradiol, testosterone, and cortisol, are just a
few of the steroid hormones coursing through your blood right now.

Ok, I know what you are thinking. Steriods are lipids and lipids hate water. So how do we get all of these hormones to dissolve in our waterbased blood? The answer is that there are these protein carrier molecules (yes, proteins again) that can bind temporarily to steroids to give
rise to an adequately hydrophilic complex that moves readily through the blood. Why then, you might ask, are steroids so popular as hormones if it takes so much effort to get them to circulate. The answer there is that steroid hormones are somewhat unique in that their nonpolar nature allows them to pass easily through a cell membrane. As we will see later on, most signaling molecules have to activate receptors on the outside of a cell membrane if they want to induce any effects on the inside of the cell. These receptors then relay the signal to
the inside of the cell. With Steroids, its more direct. Steroid hormones just flow right in and work directly with the cellular machinery inside the membrane. Nother video for you:
Steroid hormone entering a cell

Proteins
Finally, we get to proteins. Proteins are commonly called the cogs of physiology. They do all sorts of things from facilitating reactions, to
killing bacteria, to literally moving stuff from place to place. Proteins are all longish strings of amino acids held together with peptide
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bonds18. There are 20 different amino acids 19, and they can be arranged in almost any order and to almost any length. So there are a lot of
potential proteins that can be synthesized. These 20 amino acids have various chemical properties20 that they can impart to a particular
protein. Some are polar, some neutral, some hydrophobic, some acidic, some basic, and some have long electrically-charged side chains.
These properties allow amino acids within a protein to interact with each other and with stuff that encounters the protein. In this way proteins can interact with other molecules in their surroundings. Sometimes proteins even change their configuration in response to a particular molecule, or a change in pH, or even an electrical charge.
When we talk about how protein work, we generally refer to four levels of structural organization21. The primary structure22 of a protein is its sequence of amino acids.

The secondary structure is formed when hydrogen bonds are formed among the amino acids between an amine hydrogen and a carbonyl
oxygen. These bonds can cause the amino acid chain to form coils and sheets.

So now we have some three-dimensional structure, but the secondary structure does not fully define the protein; this happens when the
protein is folded into its tertiary form. The tertiary structure is formed when different bonding interactions occur, across distant members
of the amino acid chain, folding the protein into what is called its conformational shape. This shape is key; when proteins are not in this conformational shape they do not function properly.

A hemoglobin subunit

Some proteins, but not all, also have a quaternary structure. This structure emerges when different protein subunits combine to form a
larger protein structure. For example, hemoglobin, the oxygen carrying protein in your blood, is composed of four subunits.

Hemoglobin composed of four subunits (each a different color)

The folding process is spontaneous for most proteins, but some rely on other proteins to act as molecular chaperones and assist in assuming the correct tertiary structure. Heat-shock proteins 23 24 are one example of molecular chaperones. Because proteins are very sensitive
to heat, these heat shock proteins are present to prevent or correct damage cause by misfolding.
Given all of the potential variation in the structure and chemical properties of proteins, it should not be surprising that they play a major
role in almost every biological process. Here are a few of the functions carried out by proteins:
FUNCTIONAL: Enzymes, Transport, Channels.
SIGNALING: Millions of signaling molecules and receptors.
IMMUNITY: Antibodies and compliment proteins
ENERGY STORAGE: Protein catabolism
STRUCTURAL: Microtubules and other filaments. [/ref].
We will see how proteins carry out these roles as the semester progresses.

Nucleic Acids
Last, but certainly not least, we have the nucleic acids. In their simplest form nucleic acids are monomers25, with a three-part structure
composed of a sugar, a phosphate, and a nitrogenous base.

These monomers are also called nucleotides, and they are the basic building blocks of deoxyribonucleic acid or DNA2627, which you are
probably familiar with from previous coursework. The phosphate and sugar components are constants for all nucleotides, but the nitroge-

nous based can vary among several different types. DNA is made up of four types of nucleotides that are defined by four different bases:
adenine, guanine, thymine, and cytosine

RNA, or ribonucleic acid28, is similar to DNA except that it uses a nucleotide with a urasil base in leu of thymine.

Nucleotide with a
uracil base

RNA and DNA are the foundations for genetic information storage and inheritance and serve as the substrate for converting information in
the form of amino acid sequences into cellular structures and machinery29.
Nucleic acids do not just appear in DNA. One extremely important molecule derived from a nucleic acid is adenosine triphosphate or
ATP30. ATP is the main energy currency in virtually all physiological processes. ATP consists of an adenosine base and three phosphate
groups that are held together by pyrophosphate bonds. Those three phosphate groups have negatively charged oxygen atoms that really
hate each other (Molecularly speaking, opposites attract and likes repel). So when the three phosphate groups are crowded together its
like storing energy by compressing a spring.
ATP

Under the right conditions, one of the high-energy bonds can be broken, releasing energy that can be harnessed to do cellular work. When
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this happens, ATP is hydrolyzed31 and it becomes Adenosine diphosphate (ADP). Reattaching phosphate groups to ADP is a central goal of
cellular respiration.
A second energy carrying nucleic acid is nicotinamide adenine dinucleotide, NAD+ (or NADH, the difference being an oxidative reaction,
NAD+, or a reduction reaction, NADH) 32. These molecules are used for ATP production due to their ability to carry high-energy hydrogen
atoms.
So, nucleic acids encode information and they are part of energy storing/transporting molecules. One other thing about nucleic acids is that
they can be catabolized for energy. They are not as readily broken down as proteins, lipids, and carbohydrates, so they dont contribute a
lot to our energy budget. Moreover, with all of that nitrogen in their bases, catabolism of nucleic acids gives rise to a lot of potentially harmful nitrogenous wastes that have to be disposed of. So, nucleic acids are available as an energy source, but are not generally the first choice.
Putting it all together
These four basic kinds of molecules along with a few other materials can do some amazing things. Heres a really good video that depicts
some of the processes that go on inside cells all the time. See how many times you can identify something as one of the four biomolecules.

Inner Life Of A Cell - Full Version.mkv

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