The Molecules of Life

(Note: the following summary is for educational purposes only. Many of the figures are taken from different textbooks of biochemestry (e.g. Lehninger’s ‘Principles of Biochemistry (5th edition)‘) or cell biology (e.g. Albert’s ‘Molecular Biology of the Cell‘ or Lodish’s ‘Molecular Cell Biology‘). Other figures are taken from different internet sources)

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Introduction

All life forms, from single cell to multicellular organisms, strictly maintain an internal environment that is chemically different from the external environment. This inner chemical environment is capable of carrying out the most basic functions of life: building cells and tissues, producing energy, transporting solutes into and outside cells, multiplying, communicating with other cells, and so on. Some cells and tissues are also capable of carrying out less common tasks, such as motion and detoxification of foreign elements.

What is it which makes the inner environment of living cells and tissues so different than the one outside? A comparison between the two environments shows that both are built from the same chemical elements (Figure 1):

Figure 1

However, a closer look reveals that living organisms are enriched with the elements carbon (C) and hydrogen (H). Animate matter contains large quantities of oxygen and minerals like silicon, but only minute quantities of carbon and hydrogen. What is the significance of that? – it mainly has to do with the ability of carbon to form four chemical (covalent) bonds. This property allows carbon to accomplish two important feats (Fig. 2). The first is to create linear or branched chains by binding other carbon atoms (arrow 1 in Fig. 2), and the second is to create diverse chemical combinations by binding oxygen (O), nitrogen (N) and sulfur (S) (arrow 2 in Fig 2). Both of these capabilities allow carbon-based molecules to be complex and chemically diverse.

 

Figure 2

Many of the carbon-based molecules in living organisms are relatively small but still have multiple functions. Here are some examples:

  • Organic acids and bases create a chemical balance that determines the pH of the cytoplasm and organelles.
  • Sugars, amino acids and fatty acid serve as fuel for our cells to produce energy.
  • Adenosine triphosphate (ATP) serves as the energy currency of cells. It temporarily stores the energy produced from the breakdown of sugars, amino acids and fatty acids, and deliver this energy to any cellular process that requires it.
  • Certain small molecules, e.g. citrate, serve as molecular regulators that allow the cell to control the rate of its numerous processes according to the environmental conditions.
  • Similarly, molecules such as phosphate and coenzyme A attach covalently to metabolites and activate them for subsequent chemical reactions.

Some of the small carbon-based molecules possess another important property – the ability to self-assemble into larger molecular structures, termed ‘macromolecules’. There are four types of macromolecules in living organisms: proteins, nucleic acids, lipids and polysaccharides (a.k.a. carbohydrates or sugars). Each of these is built from its own basic set of small molecular building blocks (Fig. 3):

  • Proteins are built from amino acids
  • Nucleic acids are built from nucleotides
  • Lipids are built from fatty acids and/or cholesterol
  • Polysaccharides are built from simples sugars (monosaccharides)

Figure 3. Macromolecules are built from simpler molecules

Macromolecules are very common in cells and tissues (Fig. 4), and for a good reason too; these complex molecules, especially proteins and nucleic acids, are what makes living matter so unique. They are complex and diverse enough to carry out complicated tasks, and the integration of these tasks ultimately translates to what we call ‘life’. Their most basic roles are as follows (a more detailed description is given in later sections):

  • Many proteins act as enzymes – molecular machines that allow virtually all cellular processes to occur by speeding them up. Other proteins build large structures within cells (e.g. the cytoskeleton) and outside them (e.g. the extra-cellular matrix), which confer physical strength to the cell, protect it, facilitate organelle movement, and more. Another large group of proteins serve as receptors. These reside on the surface of cells and bind chemical messengers that are sent from other cells. This form of communication may have dramatic results on the cell receiving the massage, such as growth, multiplication and even death. Yet, there are proteins that fulfill more esoteric roles. For example, antibodies are proteins secreted by cells of the immune system and function to identify and sometime neutralize potentially hazardous foreign elements.
  • Nucleic acids, namely DNA and RNA, are responsible for the coding and execution of the organism’s genetic plan.
  • Lipids build the cell’s membrane, a structure which separates the cells from its external environment and facilitate transport of solutes and communication. They also serve as long-term energy stores in animals, and as a source of many bioactive compounds.
  • Polysaccharides act as short-term energy stores in animals and plants, and also build complex structures that protect its cells, such as the bacterial/plant cell wall and the exoskeleton of insects.

 

Figure 4

 

Proteins

Proteins are the most complex and functionally diverse macromolecules in all living organisms. They fulfill numerous roles in each of our cells, and are largely responsible for the vast functions of life. A detailed description of protein structure and function is given in the next page. A detailed description of amino acids is given here.

 

Figure 5. A large protein complex

 

Polysaccharides

Polysaccharides, commonly known as ‘sugars’ or ‘carbohydrates’, are polymers of simple sugars called monosaccharides:

Figure 6. The structure of a polysaccharide

The basic structure of a monosaccharide includes a carbon skeleton with multiple hydroxyl (OH) groups and one carbonyl (C=O) group. If the latter is an aldehyde, the sugar is called ‘aldose’, and if it is ketone it is called ‘ketose’:

Figure 7. The basic chemistry of a monosaccharide

Monosaccharides may be of different lengths, although the most common contain 5 or 6 carbon atoms:

Figure 8. Six-carbon aldoses.

In watery solutions (e.g. the cell’s cytoplasm, the extra-cellular environment, blood, etc.), monosaccharides of 5-6 carbons tend to form a 5 or 6-membered ring. This process changes the ketone/aldehyde group of the molecule into a hydroxyl (OH) group, which may point up or down with respect to the ring’s plane:

Figure 9. The formation of a ring structure in glucose.

The ring that is formed is not planar; it may have the shape of a boat or a chair, with the former being more stable:

Figure 10. The two dominant forms of the monosaccharide ring.

Cells and tissues also contain chemical derivatives of monosaccharides. For example, N-acetylglucosamine, an amino sugar created by attaching an acetamide moiety to glucose (Fig. 11), is an important component of the bacterial cell wall, as well as of chitin (the material building the outer covering of insects). It also participates in building the sugary cover of many secreted proteins called ‘glycoproteins’. The involvement of sugar derivatives in complex carbohydrates is further discussed below.

Figure 11.

Two monosaccharides may attach to each other via a ‘glycosidic bond’, to form a ‘disaccharide’:

Figure 12. The creation of the disaccharide maltose from two glucose units

When multiple monosaccharides interact in this way, a polysaccharide chain (linear or branched) is formed.

Polysaccharides have several roles. Here are some examples:

  • Energy stores: glycogen and starch (Fig. 13a) are two different polymers of glucose, the former exists in animal tissues and the latter in plant tissues. As mentioned above, glucose is regularly broken down by cells to produce energy. Thus, both glycogen and starch serve as stores of energy.

Fig.13

Figure 13a. Starch inside a plant cell.

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  • Physical protection: cellulose and chitin (also polymers of glucose) create tough structures that protect the organism. Cellulose creates the cell wall of plants, whereas chitin creates the outer covering (exoskeleton) of insects. While cellulose is a polymer of glucose, chitin is made of repeating units of N-acetylglucosamine that are bound to each other by β-1,4 bonds (Figure 13b). Another sugar-based structure, called peptidoglycan, forms the bacterial cell wall. The structure of peptidoglycan is made by crossing carbohydrate and peptide chains (Figure 13c). Like chitin, the carbohydrate chains of peptidoglycan include N-acetylglocusamine, but they also include sialic acid (N-acetylneuraminic acid), an acidic sugar that appears also in glycoproteins (see below) and functions in biological recognition. The peptide chains of peptidoglycan include D-alanine, an uncommon isomer of the protein building block L-alanine. The chemical crossings between the carbohydrate and peptide chains of peptidoglycan are made by an enzyme that is the target of penicillin and other beta-lactam antibiotics.

Fig.13b

Figure 13b. The disaccharide unit of which chitin is composed

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Fig.13c

Figure 13c. The structure of peptidoglycan

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  • Protein coating: carbohydrates may form a coating around proteins and peptides. These protein-sugar conjugates are separated to glycoproteins and proteoglycans. In the former, the protein is the dominant component of the molecule, whereas in the latter the carbohydrate chains are the dominant component (Figure 13d). Both glycoproteins and proteoglycans are secreted by cells and form the extra-cellular matrix. Glycoproteins also function as extracellular enzymes, antibodies, and as a part of the plasma membrane of cells. The sugar coating of these molecules helps to protect them, as well as to increase their water solubility. Furthermore, at least in the case of glycoproteins, the sugar coating is also believed to function as a ‘molecular code’ helping the specific recognition of the protein by other elements. In proteoglycans, the carbohydrate component is made of glycosaminoglycans (a.k.a. mucopolysaccharides). Glycosaminoglycans are long, unbranched polysaccharides, built from repeating disaccharide units. These units are composed of an amino sugar covalently bonded to an acidic sugar or to galactose (Figure 13e). The sugar units in glycosaminoglycans usually contain many anionic groups like sulfate, phosphate and carboxylate, which render the entire molecule negatively charged. Common glycosaminoglycans include hyaluronate (most common), keratan sulfate, chondroitin sulfate and heparin. In the structure of proteoglycans the glycosaminglycan structure includes a main chain made of hyaluronate and side chains made of keratan sulfate, chondroitin sulfate and similar molecules.

Fig.13d

Figure 13d. The structure of proteoglycan

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Fig.13e

Figure 13e. Common glycosaminglycans

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  • Lipid coating: glycolipids are lipid-sugar conjugates that can be found in cellular membranes. As in glycoproteins, the sugar coating is believed to function as a molecular code. A famous example is the blood groups (A, B, O), which are different forms of glycolipids that protrude from the membrane of red blood cells.

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Nucleic Acids

Nucleic acids include deoxy-ribo-nucleic acids (DNA) and ribo-nucleic acids (RNA).

DNA forms the genetic plan of living cells and organisms, whereas RNA takes part in the translation and execution of this plan. Both DNA and RNA are made of nucleotides, each of which includes three parts: a sugar, a base, and 1 to 3 phosphate groups (Figure 14).

Figure 14. The structure of a nucleotide.

The base portion of nucleotides may be one of five types:

Figure 15. Types of nucleotide bases.

Nucleotides, aside of constructing nucleic acids, also have other functions. For example:

  • Co-enzymes – nucleotides like NADH, NADPH, FADH2 and FMNH2 bind to enzymes and help them to catalyze chemical reactions. The role of the co-enzyme is to carry out a specific function that the protein’s amino acids are either incapable of doing or just do not do it efficiently enough.
  • Energy currency – ATP (see above)
  • Molecular switches – GTP is a nucleotide that regularly binds to a cellular communication protein. This allows the protein to carry out its specific function. While bound to the protein, the GTP molecule breaks down after a while, which changes the protein back to its inactive state. Thus, GTP acts as a switch that controls the protein’s activity.
  • Means to activate cellular metabolites – UDP is a nucleotide that binds to glucose, thus activating it for the production of the polysaccharide glycogen.

Nucleotides form nucleic acids by binding to each other via their OH and phosphate groups, to form long strands:

Figure 16. Covalent binding of nucleotides forms a long strand.

 

In the case of DNA, two such strands assemble together to form the well-known double helix structure:

Figure 17. DNA structure

In this structure, the hydrophilic (‘water-loving’) sugar-phosphate backbones of the two DNA strands are exposed to the surrounding water, and the bases are buried inside. The bases on one strand of the DNA structure interact with those in the other strand by forming hydrogen bonds. Adenine always interacts with thymine, whereas guanine always interacts with cytosine (Fig. 18). Thus, the sequence of nucleotides in one strand is always complementary to the sequence in the other strand, so as to maintain the specific hydrogen bonding pattern.

Figure 18. Hydrogen bonds between two interacting DNA strands.

In eukaryotic cells, DNA folds onto itself to form a highly condensed structure called ‘chromosome‘:

Figure 19 The folding of DNA to form a chromosome.

The long chromosomal DNA structure is composed of functional units called genes. Each gene codes a different cellular function. In fact, most genes hold the plan of producing proteins, each gene coding for a specific proteins that has a specific role. Thus, if the cell and its numerous proteins were the ‘hardware’, DNA is the ‘software’. Other genes store information to produce functional RNA molecules.

RNA is different from DNA in several ways:

1. Its sugar part is an oxy-ribose instead of a deoxy-ribose.

2. It contains uracil instead of thymine.

3. It forms more diverse structures than DNA (see two examples in Fig. 20).

Figure 20. Two of the structurally diverse RNA forms.

The structural diversity of RNA allows it to fulfill more diverse functions than DNA. Furthermore, the OH group at the second carbon of RNA sugar components makes the molecule more reactive than DNA. All of the above allows RNA to fulfill different cellular functions, whereas DNA fulfills only one.

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Lipids

As in the case of saccharides, lipids too can be simple or complex. The thing all lipids have in common is being hydrophobic (‘water-hating’). That is, all lipids repel water and ‘prefer’ to be around each other.

Two common simple lipids in eukaryotes are fatty acids and cholesterol. Fatty acids are composed of a long hydrophobic carbon skeleton with a single hydrophilic carboxyl (COOH) group at the top (Figure 21). This makes fatty acids amphipathic. That is, they have a hydrophobic part on one side and a hydrophilic part on the other side. As we will see below, this property is what allows fatty acids to build complex lipid structures. Some fatty acids have all their aliphatic carbon atoms connected by single bonds (‘saturated’), whereas others have one or more double bonds (‘unsaturated’).

Figure 21. The chemical structure of fatty acids.

Saturated fatty acids are more common in animal tissues, whereas unsaturated fatty acids are more common in plants. Being overall hydrophobic, fatty acids tend to cluster together, where they can burry their aliphatic carbon tails away from the surrounding water. Saturated fatty acids are linear and therefore tend to form condensed layered structures called ‘fat’ (Fig. 22). In contrast, the kinks in the structure of unsaturated fatty acids do not allow such condensation, and as a result they form a looser structure called ‘oil’. Increased consumption of saturated fats correlate with the occurrence of cardiovascular disease, due to the elevation of blood LDL and triglyceride levels (see below).

Figure 22. Structures formed by saturated and unsaturated fatty acids.

Some fatty acids have specific functions. For example, arachidonic acid, a 16-carbon fatty acid with four double bonds, is the source of a group of biologically active compounds called eicosanoids. These compounds, which include prostaglandins, prostacyclins, thromboxanes and leukotriens, are local mediators of fever, inflammation, pain and coagulation. Indeed, the enzymes producing eicosanoids from arachidonic acid are the target of anti-inflammatory drugs such as steroids (e.g. cortisone) and non-steroidal drugs (e.g. aspirin, ibuprofen).

Fatty acids also serve as components of complex lipids. One such lipid is triacylglycerol, commonly called ‘triglyceride’. This structure is formed by the esterification of three fatty acids to a single glycerol molecule (Figure 23). The esterification blocks both the OH groups of glycerol and the fatty acids’ carboxyl groups. As a result, triacylglycerol is completely hydrophobic.

Figure 23. Triacylglycerol

Triacylglycerol serves as a long-term form of energy storage in animals. Being completely hydrophobic, it is efficiently stored away from water in specialized tissues called ‘adipose tissues‘. When lipid-consuming tissues, such as resting muscles, are in need of energy, triacylglycerol molecules in adipose tissues are degraded and the resulting free fatty acids are mobilized to their target tissue where they are broken down and oxidized.

Another structure that is commonly formed by fatty acids is phospholipid. As triacylglycerol, the phospholipid molecule is formed too by esterification of fatty acid to a glycerol molecule. However, only two of the three carbons of the latter are esterified, whereas the third is attached to a phospho-alcohol group (Fig. 24). This makes phospholipids even more amphipathic than fatty acids.

Figure 24. Phospholipid structure.

In contrast to tryacylglycerol, phospholipids do not serve as energy storage. Being amphipathic, they are physically driven to assemble into a structure called ‘lipid bilayer‘, which allows them to keep their hydrophobic tails together, while exposing only their hydrophilic head groups to the surrounding water (Fig. 25).

Figure 25. The lipid-bilayer core of the plasma membrane.

This structure is the core of one of the most important cellular components– the plasma membrane (Fig. 26). The latter is formed when proteins are integrated within the lipid bilayer. These proteins serve as ion channels, solute transporters, receptors, and in some cases even antibodies

Figure 26. The complete structure of the plasma membrane.

Another common lipid in eukaryotes is cholesterol. The structure of this molecule includes four fused rings, a hydrophobic tail and a single OH group which makes it weakly amphipathic (Fig. 27).

Figure 27. The structure of cholesterol.

Despite its bad reputation, cholesterol is an important molecule in animal cells and tissues. Specifically, it has two main roles:

  • Constituting an integral component of the plasma membrane (see Fig. 26). This results from the amphipathic nature of cholesterol.
  • Being the source of several key biologically active compounds. These includebile acids, steroid hormones (e.g. cortisol, estrogen, progesterone, testosterone) and vitamin D.

In the blood, cholesterol is transported inside a lipid ball called ‘lipoprotein’ (as the name suggests, this structure also contains a protein element). One of the 3 forms of cholesterol-carrying lipoproteins, called LDL, is associated with cardiovascular disease. In fact, LDL itself is not the problem, as it is transported into cells in a highly regulated manner. However, when cholesterol is consumed in large quantities, LDL stays in the blood long enough to become oxidized and it is subsequently taken by macrophages (white blood cells that remove waste and foreign bacteria from the body). These cells infiltrate the endothelium of arteries and die there. The induces an inflammatory process that ultimately blocks the artery and creates blood clots. When this happens in the arteries feeding the heart (‘coronary arteries’), it may eventually result in myocardial infarction, i.e. a heart attack.

4 Responses

  1. It’s actually a nice and useful piece of info. I’m happy that you simply shared this
    helpful information with us. Please keep us up to date like this.
    Thank you for sharing.

  2. Hey bud, you have errors on your amino acid chart!!

    first you have aspartate (aspartic acid) twice on your chart. so obviously you are missing an amino acid. this would be arginine. so in polar remove aspartate, add asparagine. In pos charged theres no asparagine its supposed to be arginine. Just thought you should know as your chart is like the first to show up on a search of the 20 amino acids.

    Regards,
    Jake Husk
    Biochemist – OSU

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