Living Molecules

This is another page with a lot of information, way more than can be memorized all at once. Who knew biochemistry could be complicated? 🙃

Proteins

Proteins are very important for life. They come in many shapes and sizes and perform a tremendous array of functions. All enzymes are proteins, as are all the various receptors, ion channels, and some of the naturally occurring structural materials such as collagen and keratin. Proteins are encoded by genes according to the genetic code.

A protein is a peptide, and a peptide is a chain of amino acids joined together head to tail. There are 20 amino acids common to the vast majority of earthly life:

Alanine	Cysteine	Arginine	Lysine
Glycine	Methionine	Asparagine	Aspartic acid
Leucine	Isoleucine	Glutamine	Glutamic acid
Valine	Proline	Serine	Threonine
Phenylalanine	Tryptophan	Tyrosine	Histidine

Two things are apparent from these structures. One, they all contain at least one positive charge, on the amino group, and at least one negative charge, on the carboxyl. Molecules that have both a positive and a negative charge are called zwitterions. All of the amino acids are zwitterions beecause they are more stable when self-ionized in this way.

The second obvious thing is that all but one of the amino acids are asymmetrical. The solid wedge-shaped bonds are pointing out towards you, and the sort of grayish line bonds are pointing away into the distance. If we looked at the structure of alanine in a mirror, the result would be an isomer that cannot rotate to be the same as the original. The amino acids are chiral, from the Greek word for "hand". They occur in "left-handed" and "right-handed" forms, called enantiomers. Only glycine is achiral and has no enantiomers. One interesting property of chiral compounds is if polarized light be shone through a single enantiomer, the direction of the polarized light will rotate. Isomers that rotate the light counterclockwise are called l- or levo- isomers, and those that rotate it clockwise are d- or dextro- isomers. Amino acids are named D- or L- isomers depending on their similarity to d- or l- glyceraldehyde:

All chiral amino acids in earthly proteins are the L- enantiomer. Makes it easier to put proteins together when every subunit has the same handedness.

Proteins are joined together by peptide bonds, which are just like the bonds that we saw in nylon in the previous section. Peptide bonds are nearly always in the trans- configuration. Here is an example of a peptide, specifically a strand of polyalanine:

All of our proteins are made up of strands like this, with varying protruding groups called side chains, each strand bent and kinked and coiled into some complex shape that enables it to do its function. Side chains are what distinguishes the amino acids apart, and each amino acid unit in a protein is called a residue.

The different amino acids have their own distinctive properties. Each one brings something different to the proteins they form part of. Alanine is very good at making coils called alpha helices. The alpha helix is a very common structural feature in proteins, it is stable and resists bending or unraveling, and it offers a regularity and predictability of where the side chains will appear. Cysteine (rhymes with "sixteen") forms disulfide cross links, where two cysteine side chains become oxidized together, removing the hydrogens from their sulfur atoms, and bonding the sulfurs to each other. The result is called cystine (rhymes with "this mine") and functions not only to hold the shape of free floating proteins, but also makes nails, skin, and hair as strong as they are.

Aspartic and glutamic acids are great for when ya just want an acid. Arginine and lysine are both very basic, that is, alkaline. Someone once asked me how can they be amino acids if they're basic? Well, consider how even though p-methylphenol (p-cresol) is phenol with a methyl group added, it's not phenol and isn't corrosive like phenol is. So too an amino "acid" can be a base just because it has the molecular structure of an acid with basic stuff added to it. But great question, and it actually had me at a loss at first. Arginine is more basic than lysine; that strange conjugated triangular thing is a guanidino group, which is known for being strongly alkaline in general. Acidic and basic side chains of a protein sometimes attract each other, making contact and forming what's called a salt bridge.

Glycine is very flexible and can create a loose section in a strand. Proline is the opposite in that it's mostly rigid and also it kinks the strand. Both have a tendency to interrupt alpha helices, but for opposite reasons: too tight vs. too loose. Both are abundant in hair and fur. Methionine mostly just offers a flexible hydrophobic side chain, good at getting out of the way of any variable molecules that might get inside of, say, a receptor or an enzyme. It also participates in methylation, where it can under the right conditions give up its methyl group and plaster it onto some other molecule. The residue left behind is called homocysteine, I don't know why. It's cysteine with an extra methylene unit. Valine, leucine, and isoleucine are also mainly just hydrophobic side chains. They're good at forming van der Waals contacts with other molecules. Leucine is more stiff, isoleucine is more flexible (but not as flexible as methionine), and valine is more small and out of the way (but not as out of the way as alanine or glycine are).

Serine, threonine, asparagine, and glutamine all have polar uncharged side chains, meaning they like water but aren't acidic or basic. They're often found on the outsides of proteins compared to hydrophobic side chains usually located on the inside. Asparagine and glutamine are particularly hydrophilic.

Histidine is weakly basic and humans usually group it with lysine and arginine in lists of amino acids. But under most conditions it's actually uncharged and hydrophobic. The polarities of the C-N and C=N and N-H bonds aren't quite enough to make it hydrophilic when it's not protonated. Histidine is actually one of the aromatic (conjugated, not smelly) amino acids, with its imidazole ring. It also has a unique function in enzymes; that C=N double bond can jump to the other nitrogen atom, causing it to expel its hydrogen and leaving room for the first nitrogen atom to gain a hydrogen. This is actually a very useful feature for enzymatic activity, because it can move protons around and influence chemical reactions. And it wouldn't be possible if the ring were basic and protonated at biological pH! The other aromatic aminos are phenylalanine (plain aromatic), tyrosine (like phenylalanine but capable of hydrogen bonds), and tryptophan (like phenylalanine but bulkier; the nitrogen doesn't really do anything). Since tyrosine's hydroxy group is conjugated to its aromatic ring, the hydroxy stays nearly coplanar with the ring most of the time.

Carbs

Carbohydrates are chiral too. Check out the difference between D-glucose (dextrose) and its enantiomer:

D-glucose

L-glucose

The carbon with two oxygens bonded to it is numbered 1. Carbons 1 through 5 form part of the ring; carbon number 6 is the one with two hydrogens. The numbers are important for how carbohydrate subunits connect together to make larger molecules. Glucose has an advantage over other sugars in that its 3-dimensional structure can easily place all the ring hydroxy groups, and the 6-group, in the equatorial position. The 1-hydroxy group can tautomerize to either the equatorial or the polar position; if it is polar, the molecule is in the alpha form, and if it is equatorial, it is in the beta form.

D-Glucose is widely found in nature while L-glucose is rare. Both sugars have a sweet taste, but L-glucose cannot be metabolized by the human body.
Glucose is a hexose, meaning it has six carbon atoms. It is also an aldose, meaning it also exists as an aldehyde:
The open-chain aldehyde form and the closed-ring form freely interconvert; they are tautomers.
Hexoses have not just one chiral center (i.e. asymmetrical atom capable of forming enantiomers) but four. Consequently, there are eight aldohexoses, differing in the relative handedness of three of the chiral centers: allose, altrose, galactose, glucose, gulose, idose, mannose, and talose. Each aldohexose has its own D- and L- enantiomers. Not all aldohexoses occur in nature.

Besides aldohexoses, there are the aldopentoses arabinose, lyxose, ribose, and xylose; aldotetroses erythrose and threose, and one aldotriose which is glyceraldehyde. Besides aldoses, there are ketoses, which exist not as open-chain aldehydes and closed rings but instead as open-chain ketones and closed rings. The important ketoses are all 2-ketoses, meaning the keto group is on the second carbon atom. Here are two example ketoses, a ketotetrose and a ketohexose, and an important derivative of the latter:

erythrulose

fructose

sucrose

Sugars are simple carbohydrates. They are water soluble and quickly metabolized by the body. Complex carbohydrates are insoluble. Examples of complex carbohydrates include cellulose and amylose (starch). Cellulose consists of glucose subunits linked in what's called the β(1→4) configuration. The letter beta means the 1-oxygen is in the beta (equatorial) position. The numbers refer to which oxygens are joined together: the 1-hydroxy of one subunit is joined to the 4-hydroxy of the next, with removal of a water molecule, so that both subunits share one oxygen atom.

Starch is made up of two components: amylose, consisting of α(1→4)-joined glucose subunits, and amylopectin, a branched variation of amylose that has additional α(1→6)-joined units. Humans can digest starch, particularly amylopectin, but cannot digest cellulose. That small detail of polar vs. equatorial oxygen makes all the difference between a nutrient and inert roughage.

Chitin, the main ingredient in not only mushrooms but also the exoskeletons of bugs and crabs, is also a complex carb — kind of. Instead of being made from glucose, it is made from subunits of N-acetylglucosamine. Glucoseamine has the 2-hydroxy replaced with an amino group, and acetyl just means there's a COCH₃ group attached. Here's what that looks like:

Otherwise, chitin resembles cellulose in having β(1→4) linkages. Pretty cool that the world's two most abundant natural polymers (cellulose is first) are almost the same thing! Except they're not quite almost the same, since humans can digest tiny pieces of chitin. Imagine that.

Fats

Fats have a simpler molecular structure than either proteins or complex carbs. Fats are basically an organism's way to store hydrocarbon fuel that can easily be broken down and burned (i.e. oxidized to water and carbon dioxide with a release of energy) at body temperature inside the cells. It is no coincidence that fats and hydrocarbons are usually miscible, meaning they easily mix together.
Fats are esters of glycerine and fatty acids.
Here's an example of a fat molecule, namely glyceryl trioleate, or the ester of glycerine and three oleic acid molecules:

An ester of glycerine with three fatty acid molecules is called a triglyceride. There are also diglycerides and monoglycerides, with only two or just one fatty acid chain, respectively. The trioleate fat shown above is an example of a cis-monounsaturated fat. There are also trans fats, which have straight chains, conjugated fats, and polyunsaturated fats with multiple double bonds in the chain. Polyunsaturated fatty acids tend to have all-cis double bonds separated by only a single methylene (i.e. -CH₂-) group, so the chain has no choice but to curl. One example of a cis-polyunsaturated fat is the alpha-linolenic acid triglyceride:

Genetic Material

Everyone has heard of the four nucleotides of DNA called ATGC, and some of us know that RNA uses a fifth nucleotide U in place of T. Why? I dunno. Why does DNA use deoxyribose instead of normal ribose like RNA does? Why do they have to be different? No matter, here are the four five nucleotides:

Adenine

Thymine

Uracil

Guanine

Cytosine

DNA nucleosides contain deoxyribose, that is, ribose missing one oxygen atom. RNA nucleosides contain normal ribose. A nucleotide is a nucleoside with a phosphate attached to the 5'-carbon.

Deoxyadenosine, a DNA nucleoside

Adenosine, an RNA nucleoside

Adenosine monophosphate (AMP), a nucleotide

Adenosine triphosphate (ATP), a carrier of energy

DNA and RNA sequences are read from the 5' end to the 3' end. Similar to glucose, you can identify which carbon is the 1-carbon of ribose or deoxyribose in a nucleotide because it used to have two oxygen atoms attached to it, except one of them has been replaced by a nitrogen of the base.

(I'm not sure whether it's possible to get the skeletal formula drawing utility to show you some DNA paired together all nice. I also can't spell what I wanted to spell using RNA, since there's no T. But here's an unraveled RNA strand anyway. Since it's in a disorderly state, it's what's called denatured.)

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