SS5 Script Organic Molecules

Organic Molecules

ORGANIC MOLECULES AND MACROMOLECULES. In this lecture, I introduce the major macromolecules associated with living organisms. Molecules that contain carbon are referred to as organic molecules. Carbon is an important atom in biology due to its unparalleled ability to form long, complex molecules that are central to organisms form and function.

FORMATION OF BONDS WITH A CARBON. Carbon has four unpaired valence electrons in a valence shell with a maximum capacity of eight. This allows a carbon atom to form up to four covalent bonds, as shown in this diagram. On the top, each carbon is connected to four different atoms. On the bottom, each carbon has a double bond with one of the two oxygens in carbon dioxide. There is huge diversity in organic molecules, but all predominately consist of some combination of four elements: carbon, hydrogen, oxygen, and nitrogen. Molecules that consist solely of carbon and hydrogen are referred to as hydrocarbons. Although pure hydrocarbons are uncommon in living organisms, they do form important parts of many organic molecules, which includes lipids present in cell membranes. Despite consisting solely of carbon and hydrogen, there are many different ways in which hydrocarbons can differ in their structure. This can include chains of different lengths, as linear or branched structures, or circularized into rings. They may or may not contain double bonds, and if so, the position of the double bond varies in different molecules.

CHEMICAL GROUPS: HYDROXYL Biological activities of large molecules are determined in part by the functional groups that they contain. Throughout this course, it would be helpful if you could visualize the structure of these groups because that is critical to our understanding of how molecules work. Let’s start with the hydroxyl group, which consists of an oxygen atom bound to both a proton and some sort of backbone, shown here for a sugar or monosaccharide. We discussed this concept in the lecture on water, so you should probably realize that O and H do not share their electrons equally. There is a dipole in the OH that has the H being relatively positive. This polarity allows it to form hydrogen bonds with water, which enhances solubility. The abundance of hydroxyls on sugars is what makes them so soluble in water.

CHEMICAL GROUPS: METHYL. Shown on this slide are two related compounds. One of them is estradiol, which is a type of estrogen. The other is testosterone, a type of androgen. They are built a similar ringed-carbon backbone, but differ in their functional groups. The additional methyl group in testosterone may seem like a subtle structural difference, but its enough for a cell to distinguish in determining how they respond. Later, when we talk about gene regulation, we will explore the impact of addition and removal of methyl groups on DNA and proteins. The processes of methylation and demethylation are vital ways of regulating epigenetics, or how a particular genotype manifests as a phenotype beyond the simple genetic sequence.

CHEMICAL GROUPS: CARBONYL. With 4 valence electrons, carbon molecules have the ability to form a double bond with oxygen, while also being connected to one or two other carbons in a chain. When the double bond O is at the end of the chain, the molecule is an aldehyde. When it is in the middle, it is a ketone. The two sugars in this image differ in where the double bonded oxygen occurs. Fructose is a ketose, meaning a sugar with a ketone. Glyceraldehyde is an aldose, with an aldehyde group. The presence of a terminal carbonyl prevents the sugar from becoming a ring structure, which is something possible in ketoses.

CHEMICAL GROUPS: CARBOXYL. Carboxyls are like carbonyl aldehydes, except the carbon is bound to an OH rather than an H. Here, the OH is so polar that the carboxyl can donate its H+ to another molecule, including -OH groups in water, which makes it an acid. The presence of the carboxyl is why amino acids and fatty acids are acids. Other important organic acids are metabolic intermediates, including the substrates and products of the tricarboxylic acid cycle.

CHEMICAL GROUPS: AMINO. Another polar chemical group is an amino group. Here the dipole is such that the negativity of the N is sufficient to pull a H+ off another molecule. In chemical terms, it is a base, going from an un-ionized NH2 sidegroup to ionized NH3 sidegroup. The same thing happens when ammonia (NH3) becomes ammonium or NH4+. The dipole is also sufficient to permit it to interact with carboxyl groups to create covalent bonds. The peptide bonds of proteins arise from the bonds form between an amino and a carboxylic acid group of two amino acids.

CHEMICAL GROUPS: PHOSPHATE. Another important functional group is the phosphate group, which consists of one phosphorus atom bound to four oxygen atoms. One compound that contains phosphate groups is adenosine triphosphate, or ATP for short. ATP is a crucial molecule for survival, as the reaction of ATP with water results in the cleavage of the terminal phosphate group. This reaction releases a lot of energy that is then used to provide the energy required for many cellular processes. In a later lecture we will talk more about ATP as a high energy compound in intermediary metabolism. Another aspect of phosphate that makes it important is that it can be attached to select amino acids in a protein, which dramatically affects the residue’s shape and charge. As a result, many proteins are regulated by enzymes that add or remove phosphate groups. Kinases use ATP to transfer a phosphate to another molecule, which can be removed by enzymes called phosphatases. A protein kinase is a kinase that works on a protein as a substrate. These are critical protein regulators, and they are often the mechanisms by which hormones and other cell signals change signalling and metabolic pathways, so you will hear lots about them in the coming lectures.

CHEMICAL BONDS. The four main macromolecule types relevant in biology are proteins, lipids, carbohydrates and nucleic acids. These are mostly polymers composed of strings of monomers that are created by bonds formed in dehydration reactions. The H of one molecule interacts with the OH of another. The reaction simultaneously removes a water molecule and connects the two monomers together. Many different bonds are created by dehydration, and the name of the bond is based on what two atoms are connected together. We talked about peptide bonds previously and one other bond to discuss in detail is the so-called phosphodiester bond.

BONDS VS LINKAGES. I say “so-called” bond because the terminology is not applied in a meaningful way and often creates confusion. I have Googled the topic frequently and the entries are pretty awful because they often fail to make the distinctions between bonds and linkages, and also use the most common examples as part of the definition rather than to illustrate generalities. So I will be very precise here, and once you get the distinctions, then it’s fine to slip back into common convention. A bond is a connection between two atoms arising via shared electrons. A linkage is when two atoms are connected by a third via two bonds. You may have heard of an ester bond, which is not a bond but a linkage. A ester linkage is oxygen connects two atoms, one of which is a carbon double bonded to oxygen. It typically forms when the OH of the carboxyl condenses with a hydroxyl of another molecule, so in a general sense, a carboxylic acid and an alcohol. Any alcohol would work, but in biochemistry this is most often a sugar. A phosphodiester bond also doesn’t exist, but if you talk about a phosphodiester linkage it’s the same as an ester linkage except the atom double-bonded to the oxygen is phosphorus, not carbon. In the case of nucleic acids, such as the DNA molecule on the right, you can see that the backbone is composed of sugars and phosphate. Each phosphate is connected to the sugar by a phosphoester linkage, and since the phosphate is connected to two sugars, its called a phosphodiester linkage. There is no such thing as a phosphodiester bond, but collectively the backbone relies on phosphodiester linkages. You can probably drive yourself crazy trying to decide if it is better called a diphosphester or phosphodiester, but the point here is that it's not a bond per se but a series of bonds to create the motif of a phosphate connecting two sugars.

CARBOHYDRATES. Carbohydrates are monomers and polymers of sugar. They are used for both energy generation and storage, and their breakdown also provides the carbon atoms used for building other biological molecules. In addition, carbohydrates serve roles in cell structure. A carbohydrate monomer is known as a monosaccharide. Monosaccharides can contain between three and eight carbon atoms, and generally have two hydrogen atoms and one oxygen atom for each carbon atom. Shown on the screen is the structure of glucose, which is the most common monosaccharide. Glucose, and other five and six carbon monosaccharides, can be found in either linear format or as a ring structure. In aqueous solutions, these sugars are found predominately in the ring form. There is great diversity in the types of monosaccharides that are found in nature, due in large part to the many different isomers that are possible. This includes structural isomers in which the carbonyl group differs in its position. In glucose, the carbonyl group is at the first carbon, whereas in fructose, the carbonyl group is at the second carbon position.

GLYCOSIDIC LINKAGES. Disaccharides consist of two monosaccharides that are connected via glycosidic linkages that are the result of dehydration reactions between hydroxyl group of the two monosaccharides. An example of a disaccharide is maltose, which is a dimer of two glucoses. It is a 1-4 glycosidic linkage because the bond forms between the OH at position 1 with the OH at position 4. The lower example is sucrose, known more commonly as table sugar. It consists of a glucose and a fructose monomer. Monosaccharides and disaccharides have two primary roles in living organisms, with the breakdown of these compounds resulting in a significant amount of energy, as well as the raw materials (the atoms) required for building other biological molecules.

POLYSACCHARIDES. A polysaccharide is a carbohydrate polymer that consists of 10s to thousands of monosaccharides. The main roles of polysaccharides in living organisms are as energy storage compounds and as
structural components of cells. Shown on this slide are two different polysaccharides. The upper polymer is starch and the lower one is glycogen. They are both built on 1-4 linkages with branches arising from 1-6 linkages. Starch is made by plants and glycogen by animals, but structurally they differ only in the degree of branching. Glycogen is the more highly branched than starch, which has unbranched regions and moderately branched regions.

POLYSACCHARIDES. This polysaccharide is cellulose. Like starch, it’s made of glucose polymers yet they have very different functions. These two functions can be traced back to the fact that glucose can actually be found in
two slightly different ring structures. Specifically, the hydroxyl group on carbon one can be either below the carbon ring or above the carbon ring. These two structures are known as alpha-glucose and beta-glucose, respectively. In starch, all of the glucose monomers are alpha-glucose, which allows starch to take on a helical shape and efficiently store glucose in a limited amount of space. On the other hand, cellulose consists solely of beta-glucose monomers and as a result, it is a linear molecule. This allows cellulose to form hydrogen bonds with other parallel cellulose molecules, and together these hydrogen-bonded cellulose molecules are able to provide significant structural support.

LIPIDS. Lipids share a trait of being hydrophobic and mix poorly with water. And unlike the other three classes of biological macromolecules, lipids are not polymers. Lipids can have many different functions in living organisms, including structure, energy storage, and signalling. You often hear about fats, often used interchangeably with lipids but the textbook adopts a convention of using the term fat to refer to triglycerides, which is what animals use to store energy. Triglycerides consist of three fatty acid molecules that are covalently bonded to glycerol. In these images, the yellow boxes are the fatty acids, and the grey boxes glycerol. Note that each fatty acids consists of long hydrocarbon chain that ends with a carboxylic acid. The formation of triglycerides involved dehydration reactions between the carboxylic acid group of a fatty acid and a hydroxyl group of the glycerol, and results in the formation of an ester linkage. The fatty acids connected to glycerol can differ in length, but they tend to be either 16- or 18-carbons long. Like fats, phospholipids have fatty acid chains that are connected to a glycerol molecule. However, phospholipids have only two fatty acid chains and in the third position have a phosphate group. As a result, phospholipids are amphipathic molecules. The fatty acid chains are hydrophobic and do not mix well with water, whereas the phosphate group is polar and likes to mix with water. This feature is what makes phospholipids ideal molecules for cellular membranes. The fatty acid chains are on the inner core of the membrane, while the polar phosphate heads are towards the surface of the bilayer and intact with the aqueous solution either inside or outside of the cell. We will continue the discussion of phospholipids in our lecture on cellular membranes.

LIPIDS. Another class of hydrophobic molecules considered to be lipids are steroids. The key characteristic of steroids is that they consist of four interconnected rings of carbon. An example of a steroid is cholesterol, which is a component of animal cell membranes. It is also the precursor for many signalling molecules used by animals, including the sex steroid hormones shown here, as well as the various stress hormones that control energy metabolism and water and ion balance.

PROTEINS. The last two macromolecules to explore are proteins and nucleic acids, but since they are discussed in far more detail in the core lectures, we will only introduce them here. Proteins are strings of amino acids produced in cells by the process of translation. They are made from the well known 20 amino acids, which we identify using three letter codes or one letter codes, enabling us to define the primary sequence of a protein, which is the chain of amino acids. These polymers can fold onto themselves to confer a secondary structure, producing thinks like an alpha helix. These structures can interact with each other via different sidechains to create a tertiary structure. In many cases, hydrophobic side chains on one helix will interact with other hydrophobic side chains on another, effectively burying the hydrophobic regions into a core. For many proteins, multiple isolated peptides interact to produce a superstructure of multiple distinct subunits bound together by weak bonds.

NUCELIC ACIDS. The monomers of nucleic acids are nucleotides, which consist of a nitrogenous base, a five-carbon sugar, and a phosphate group. In RNA, the sugar that is used is a ribose, while in DNA, the sugar is a deoxyribose. The difference between these sugars is that ribose contains an oxygen that is lacking in deoxyribose. In addition to differences in the sugars, nucleotides differ in their nitrogenous bases, which fall into two different categories. The pyrimidines are nitrogenous bases that consist of one ring. These include cytosine, thymine, and uracil. Note that thymine is only found in DNA while uracil is only found in RNA. The other category of nitrogenous bases are the purines that consist of two fused rings. These include adenine and guanine.

NUCLEIC ACIDS. As we discussed previously, the nucleotides of nucleic acid strands are connected via phosphodiester linkages. Nucleic acids are said to have directionality because the two ends of the polymer differ from each other. In both DNA and RNA, the end of the polymer that has a phosphate group is said to be the 5’ (five prime) end, while the end that terminates in a hydroxyl group is said to be the 3’ (three prime) end. DNA molecules consist of two strains of DNA that is said to be antiparallel, so they run parallel to each other but in opposite directions, similar to the two sections of a highway. And so the 5’ end of one strand matches with the 3’ end of the other strand. These two strands are held together by hydrogen bonding between the nitrogenous bases. Pairing is specific. Cytosine always binds with guanine, and adenine binding with thymine. In contrast, RNA molecules are generally single stranded molecules. However, they can form complex secondary structures, with hydrogen bonding forming between the nitrogenous bases of two different regions of the strand, giving the molecule a unique three-dimensional shape.