Monosaccharides

A monosaccharide is a monomer of carbohydrates. Five monosaccharides are particularly important in the body. Three of these are the hexose sugars, so called because they each contain six atoms of carbon. These include glucose, fructose, and galactose, shown in Figure 1a. These are typically disassembled to generate adenosine triphosphate (ATP), a process that will be described in detail elsewhere in this textbook.  The remaining monosaccharides are two pentose sugars, each of which contains five atoms of carbon. They are the ribose and deoxyribose (Figure 2b) molecules that make up a major component of ribonucleic acid (RNA) and deoxyribonucleic acid (DNA), respectively.

Disaccharides

A disaccharide is a pair of monosaccharides. Disaccharides are formed via dehydration synthesis, and the bond linking them is referred to as a glycosidic bond (glyco- = “sugar”). Three disaccharides (shown in Figure 2) are important to humans. These are sucrose, commonly referred to as table sugar; lactose, or milk sugar; and maltose, or malt sugar. As you can tell from their common names, you consume these in your diet; however, your body cannot use them directly. Instead, in the digestive tract, they are split into their component monosaccharides via hydrolysis.

Polysaccharides

Polysaccharides can contain a few to a thousand or more monosaccharides. Three are important to the body (Figure 3):

• Starches are polymers of glucose. They occur in long chains called amylose or branched chains called amylopectin, both of which are stored in plant-based foods and are relatively easy to digest.
• Glycogen is also a polymer of glucose, but it is stored in the tissues of animals, especially in the muscles and liver. It is not considered a dietary carbohydrate because very little glycogen remains in animal tissues after slaughter; however, the human body stores excess glucose as glycogen in the muscles and liver.
• Cellulose, a polysaccharide that is the primary component of the cell wall of green plants, is the component of plant food referred to as “fiber”. In humans, cellulose/fiber is not digestible; however, dietary fiber has many health benefits. It helps you feel full so you eat less, it promotes a healthy digestive tract, and a diet high in fiber is thought to reduce the risk of heart disease and possibly some forms of cancer.

Functions of Carbohydrates

The body obtains carbohydrates from plant-based foods. Grains, fruits, and legumes and other vegetables provide most of the carbohydrate in the human diet, although lactose is found in dairy products.

Although most body cells can break down other organic compounds for fuel, all body cells can use glucose. Moreover, nerve cells (neurons) in the brain, spinal cord, and through the peripheral nervous system, as well as red blood cells, can use only glucose for fuel. In the breakdown of glucose for energy, molecules of adenosine triphosphate (ATP) are produced.  ATP consists of a ribose molecule bound to an adenine base and three phosphate groups, and releases free energy when its phosphate bonds are broken, supplying chemical energy to the cell.  More ATP is produced in the presence of oxygen (O₂) than in carbohydrate-metabolizing pathways that do not use oxygen. The overall reaction for the conversion of the energy in glucose to energy stored in ATP can be written:

In addition to being a critical fuel source, carbohydrates are used in small amounts as part of a cell’s structure. For instance, some carbohydrate molecules bind with proteins to produce glycoproteins, and others combine with lipids to produce glycolipids, both of which are found in the membrane that encloses the contents of body cells.  The carbohydrate chains protrude outward from the cell membrane, creating a structure known as the glycocalyx (“sugar coat”) of a cell that is used in cell adhesion and recognition.  Pentose sugars are critical structural components of ATP and the nucleotides that make up RNA and DNA.

Triglycerides

A triglyceride is one of the most common dietary lipid groups, and the type found most abundantly in body tissues. This compound, which is commonly referred to as a fat, is formed from the synthesis of two types of molecules (Figure 4):

• A glycerol backbone at the core of triglycerides, consists of three carbon atoms.
• Three fatty acids, long chains of hydrocarbons with a carboxyl group and a methyl group at opposite ends, extend from each of the carbons of the glycerol.

Triglycerides form via dehydration synthesis. Glycerol gives up hydrogen atoms from its hydroxyl groups at each bond, and the carboxyl group on each fatty acid chain gives up a hydroxyl group. A total of three water molecules are thereby released.

Fatty acid chains that have no double carbon bonds anywhere along their length and therefore contain the maximum number of hydrogen atoms are called saturated fatty acids. These straight, rigid chains pack tightly together and are solid or semi-solid at room temperature (Figure 5a). Butter and lard are examples, as is the fat found on a steak or in your own body. In contrast, fatty acids with one double carbon bond are kinked at that bond (Figure 5b). These monounsaturated fatty acids are therefore unable to pack together tightly, and are liquid at room temperature. Polyunsaturated fatty acids contain two or more double carbon bonds, and are also liquid at room temperature. Plant oils such as olive oil typically contain both mono- and polyunsaturated fatty acids.

Whereas a diet high in saturated fatty acids increases the risk of heart disease, a diet high in unsaturated fatty acids is thought to reduce the risk. This is especially true for the omega-3 unsaturated fatty acids found in cold-water fish such as salmon. These fatty acids have their first double carbon bond at the third hydrocarbon from the methyl group (referred to as the omega end of the molecule).  Omega-6 unsaturated fatty acids has their first double carbon bond at the sixth hydrocarbon from the methyl group.

Finally, trans fatty acids found in some processed foods, including some stick and tub margarines, are thought to be even more harmful to the heart and blood vessels than saturated fatty acids. Trans fats are created from unsaturated fatty acids (such as corn oil) when chemically treated to produce partially hydrogenated fats.  These molecules contain double carbon bonds that are formed by removal of hydrogen atoms from opposite sides of the hydrocarbon chain, leaving the hydrocarbon chain straight rather than kinked as in the cis unsaturated fatty acids (where the hydrogens are removed from the same side of adjacent carbons) more commonly produced by living cells.

As a group, triglycerides are a major fuel source for the body. When you are resting or asleep, a majority of the energy used to keep you alive is derived from triglycerides stored in your fat (adipose) tissues. Triglycerides also fuel long, slow physical activity such as gardening or hiking, and contribute a modest percentage of energy for vigorous physical activity. Dietary fat also assists the absorption and transport of the nonpolar fat-soluble vitamins A, D, E, and K. Additionally, stored body fat protects and cushions the body’s bones and internal organs, and acts as insulation to retain body heat.

Fatty acids are also components of glycolipids, which are sugar-fat compounds found in the cell membrane. Lipoproteins are compounds in which the hydrophobic triglycerides are packaged in protein envelopes for transport in body fluids.

Phospholipids

As its name suggests, a phospholipid is a bond between the glycerol component of a lipid and a phosphorous molecule. In fact, phospholipids are similar in structure to triglycerides. However, instead of having three fatty acids, a phospholipid is generated from a diglyceride, a glycerol with just two fatty acid chains (Figure 6). The third binding site on the glycerol is taken up by the phosphate group, which in turn is attached to a polar “head” region of the molecule. Recall that triglycerides are nonpolar and hydrophobic. This still holds for the fatty acid portion of a phospholipid compound. However, the head of a phospholipid contains charges on the phosphate groups, as well as on the nitrogen atom. These charges make the phospholipid head hydrophilic. Therefore, phospholipids are said to have hydrophobic tails, containing the neutral fatty acids, and hydrophilic heads, containing the charged phosphate groups and nitrogen atom.

Steroids

A steroid compound (referred to as a sterol) has as its foundation a set of four hydrocarbon rings bonded to a variety of other atoms and molecules (see Figure 6b). Although both plants and animals synthesize sterols, the type that makes the most important contribution to human structure and function is cholesterol, which is synthesized by the liver in humans and animals and is also present in most animal-based foods. Like other lipids, cholesterol’s hydrocarbons make it hydrophobic; however, it has a polar hydroxyl head that is hydrophilic. Cholesterol is an important component of bile acids, compounds that help emulsify dietary fats. In fact, the word root chole- refers to bile. Cholesterol is also a building block of the steroid hormones, one class of signaling molecules that the body releases to regulate processes at distant sites (endocrine signalling). Finally, like phospholipids, cholesterol molecules are found in the cell membrane, where their hydrophobic and hydrophilic regions help regulate the flow of substances into and out of the cell.

Eicosanoids

The eicosanoids are lipids that are derived from polyunsaturated fatty acids with 20 carbon atoms in their hydrocarbon chain, primarily arachidonic acid.  Like the steroid hormones, they are used as signalling molecules in the body, and include prostaglandins (see Figure 6c), leukotrienes, and thromboxanes. They are often used for shorter-range signalling than steroid hormones, however, typically acting in an autocrine (affecting the cell that released them) or paracrine (affecting nearby cells) fashion.

Prostaglandins are produced by almost all nucleated cells, and serve a variety of functions.  One reason that the omega-3 fatty acids found in fish are beneficial is that they stimulate the production of certain prostaglandins that help regulate aspects of blood pressure and inflammation, and thereby reduce the risk for heart disease. Some prostaglandins also sensitize nerves to pain. One class of pain-relieving medications called nonsteroidal anti-inflammatory drugs (NSAIDs) works by reducing the effects of prostaglandins.

Leukotrienes are produced by leukocytes, and primarily mediate inflammation.  Thromboxanes are derived from a particular prostaglandin in platelets, and stimulate blood clot formation (“thrombosis”), vasoconstriction, and bronchoconstriction.

Microstructure of Proteins

Proteins are polymers made up of nitrogen-containing monomers called amino acids. An amino acid is a molecule composed of an amino group and a carboxyl group, together with a variable side chain. Just 20 different amino acids contribute to nearly all of the thousands of different proteins important in human structure and function. Body proteins contain a unique combination of a few dozen to a few hundred of these 20 amino acid monomers. All 20 of these amino acids share a similar structure (Figure 7). All consist of a central carbon atom to which the following are bonded:

• a hydrogen atom
• an alkaline (basic) amino group NH₂ (see Table 1)
• an acidic carboxyl group COOH (see Table 1)
• a variable group

Notice that all amino acids contain both an acid (the carboxyl group) and a base (the amino group) (amine = “nitrogen-containing”). For this reason, they make excellent buffers, helping the body regulate acid–base balance. What distinguishes the 20 amino acids from one another is their variable group, which is referred to as a side chain or an R-group. This group can vary in size and can be polar or nonpolar, giving each amino acid its unique characteristics. For example, the side chains of two amino acids—cysteine and methionine—contain sulfur. Sulfur does not readily participate in hydrogen bonds, whereas all other amino acids do. This variation influences the way that proteins containing cysteine and methionine are assembled.

Amino acids join via dehydration synthesis to form protein polymers (Figure 8). The unique bond holding amino acids together is called a peptide bond. A peptide bond is a covalent bond between two amino acids that forms by dehydration synthesis. A peptide, in fact, is a very short chain of amino acids. Strands containing fewer than about 100 amino acids are generally referred to as polypeptides rather than proteins.

The body is able to synthesize most of the amino acids from components of other molecules; however, nine cannot be synthesized and have to be consumed in the diet. These are known as the essential amino acids.

Free amino acids available for protein construction are said to reside in the amino acid pool within cells. Structures within cells use these amino acids when assembling proteins. If a particular essential amino acid is not available in sufficient quantities in the amino acid pool, however, synthesis of proteins containing it can slow or even cease.

Shape of Proteins

Just as a fork cannot be used to eat soup and a spoon cannot be used to spear meat, a protein’s shape is essential to its function. A protein’s shape is determined, most fundamentally, by the sequence of amino acids of which it is made (Figure 9a). The sequence is called the primary structure of the protein.

Although some polypeptides exist as linear chains, most are twisted or folded into more complex secondary structures that form when bonding occurs between amino acids with different properties at different regions of the polypeptide. The most common secondary structure is a spiral called an alpha-helix. If you were to take a length of string and simply twist it into a spiral, it would not hold the shape. Similarly, a strand of amino acids could not maintain a stable spiral shape without the help of hydrogen bonds, which create bridges between different regions of the same strand (see Figure 9b). Less commonly, a polypeptide chain can form a beta-pleated sheet, in which hydrogen bonds form bridges between different regions of a single polypeptide that has folded back upon itself, or between two or more adjacent polypeptide chains.

The secondary structure of proteins further folds into a compact three-dimensional shape, referred to as the protein’s tertiary structure (see Figure 9c). In this configuration, amino acids that had been very distant in the primary chain can be brought quite close via hydrogen bonds or, in proteins containing cysteine, via disulfide bonds. A disulfide bond is a covalent bond between sulfur atoms in a polypeptide. Often, two or more separate polypeptides bond to form an even larger protein with a quaternary structure (see Figure 9d). The polypeptide subunits forming a quaternary structure can be identical or different. For instance, hemoglobin, the protein found in red blood cells is composed of four tertiary polypeptides, two of which are called alpha chains and two of which are called beta chains.

When they are exposed to extreme heat, acids, bases, and certain other substances, proteins will denature. Denaturation is a change in the structure of a molecule through physical or chemical means. Denatured proteins lose their functional shape and are no longer able to carry out their jobs. An everyday example of protein denaturation is the curdling of milk when acidic lemon juice is added.

The contribution of the shape of a protein to its function can hardly be exaggerated. For example, the long, slender shape of protein strands that make up muscle tissue is essential to their ability to contract (shorten) and relax (lengthen). As another example, bones contain long threads of a protein called collagen that acts as scaffolding upon which bone minerals are deposited. These elongated proteins, called fibrous proteins, are strong and durable and typically hydrophobic.  Fibrous proteins are used for movement, from muscle cell contraction (actin and myosin) down to intracellular transport (e.g. actin).  They are also used to provide a structural framework or mechanical support of connective tissues (e.g. collagen, keratin, elastin), individual cells (e.g. titin), and plasma membranes (e.g. spectrin, dystrophin).

In contrast, globular proteins are shaped like globes or spheres that tend to be highly reactive and are hydrophilic. Globular proteins are abundant throughout the body, playing critical roles in most body functions. Enzymes, introduced earlier as protein catalysts, are examples of this; the next section takes a closer look at the catalytic action of enzymes, but globular proteins serve many other functions in the human body as well.

Some globular proteins are used to transport specific molecules (e.g. hormones or gases) or ions (e.g. iron or calcium) in blood.  The hemoglobin proteins packed into red blood cells for example (see Figure 9d) are used to transport the oxygen gas molecules from the lungs to other body cells. Others (e.g. albumin, hemoglobin) can help regulate body fluid pH by reversibly functioning as acids or bases, thus acting as buffers.  Some globular proteins act as hormones to regulate metabolism, and are referred to as peptide hormones or protein hormones (e.g. insulin, growth hormone, oxytocin).  Others are used to defend the body against foreign substances including invading pathogens and toxins  (e.g. antibodies, complement proteins).  Finally, some globular proteins known as molecular chaperones are essential to the production of other proteins and the appropriate breakdown of damaged proteins.

Proteins Function as Enzymes

If you were trying to type a paper, and every time you hit a key on your laptop there was a delay of six or seven minutes before you got a response, you would probably get a new laptop. In a similar way, without enzymes to catalyze chemical reactions, the human body would be nonfunctional. It functions only because enzymes function.

Enzymatic reactions—chemical reactions catalyzed by enzymes—begin when substrates bind to the enzyme. A substrate is a reactant in an enzymatic reaction. This occurs on regions of the enzyme known as active sites (Figure 10). Any given enzyme catalyzes just one type of chemical reaction. This characteristic, called specificity, is due to the fact that a substrate with a particular shape and electrical charge can bind only to an active site corresponding to that substrate.

Binding of a substrate produces an enzyme–substrate complex. It is likely that enzymes speed up chemical reactions in part because the enzyme–substrate complex undergoes a set of temporary and reversible changes that cause the substrates to be oriented toward each other in an optimal position to facilitate their interaction. This promotes increased reaction speed. The enzyme then releases the product(s), and resumes its original shape. The enzyme is then free to engage in the process again, and will do so as long as substrate remains.

Other Functions of Proteins

Advertisements for protein bars, powders, and shakes all say that protein is important in building, repairing, and maintaining muscle tissue, but the truth is that proteins contribute to all body tissues, from the skin to the brain cells. Also, certain proteins act as hormones, chemical messengers that help regulate body functions, For example, growth hormone is important for skeletal growth, among other roles.

As was noted earlier, the basic and acidic components enable proteins to function as buffers in maintaining acid–base balance, but they also help regulate fluid–electrolyte balance. Proteins attract fluid, and a healthy concentration of proteins in the blood, the cells, and the spaces between cells helps ensure a balance of fluids in these various “compartments.” Moreover, proteins in the cell membrane help to transport electrolytes in and out of the cell, keeping these ions in a healthy balance. Like lipids, proteins can bind with carbohydrates. They can thereby produce glycoproteins or proteoglycans, both of which have many functions in the body.

The body can use proteins for energy when carbohydrate and fat intake is inadequate, and stores of glycogen and adipose tissue become depleted. However, since there is no storage site for protein except functional tissues, using protein for energy causes tissue breakdown, and results in body wasting.

Nucleic Acids

The nucleic acids differ in their type of pentose sugar. Deoxyribonucleic acid (DNA) is nucleotide that stores genetic information. DNA contains deoxyribose (so-called because it has one less atom of oxygen than ribose) plus one phosphate group and one nitrogen-containing base. The “choices” of base for DNA are adenine, cytosine, guanine, and thymine. Ribonucleic acid (RNA) is a ribose-containing nucleotide that helps manifest the genetic code as protein. RNA contains ribose, one phosphate group, and one nitrogen-containing base, but the “choices” of base for RNA are adenine, cytosine, guanine, and uracil.

The nitrogen-containing bases adenine and guanine are classified as purines. A purine is a nitrogen-containing molecule with a double ring structure, which accommodates several nitrogen atoms. The bases cytosine, thymine (found in DNA only) and uracil (found in RNA only) are pyramidines. A pyramidine is a nitrogen-containing base with a single ring structure

Bonds formed by dehydration synthesis between the pentose sugar of one nucleic acid monomer and the phosphate group of another form a “backbone,” from which the components’ nitrogen-containing bases protrude. In DNA, two such backbones attach at their protruding bases via hydrogen bonds. These twist to form a shape known as a double helix (Figure 12). The sequence of nitrogen-containing bases within a strand of DNA form the genes that act as a molecular code instructing cells in the assembly of amino acids into proteins. Humans have almost 22,000 genes in their DNA, locked up in the 46 chromosomes inside the nucleus of each cell (except red blood cells which lose their nuclei during development). These genes carry the genetic code to build one’s body, and are unique for each individual except identical twins.

In contrast, RNA consists of a single strand of sugar-phosphate backbone studded with bases. Messenger RNA (mRNA) is created during protein synthesis to carry the genetic instructions from the DNA to the cell’s protein manufacturing plants in the cytoplasm, the ribosomes.

Adenosine Triphosphate

The nucleotide adenosine triphosphate (ATP), is composed of a ribose sugar, an adenine base, and three phosphate groups (Figure 13). ATP is classified as a high energy compound because the two covalent bonds linking its three phosphates store a significant amount of potential energy. In the body, the energy released from these high energy bonds helps fuel the body’s activities, from muscle contraction to the transport of substances in and out of cells to anabolic chemical reactions.

When a phosphate group is cleaved from ATP, the products are adenosine diphosphate (ADP) and inorganic phosphate (P_i). This hydrolysis reaction can be written:

Removal of a second phosphate leaves adenosine monophosphate (AMP) and two phosphate groups. Again, these reactions also liberate the energy that had been stored in the phosphate-phosphate bonds. They are reversible, too, as when ADP undergoes phosphorylation. Phosphorylation is the addition of a phosphate group to an organic compound, in this case, resulting in ATP. In such cases, the same level of energy that had been released during hydrolysis must be reinvested to power dehydration synthesis.

Cells can also transfer a phosphate group from ATP to another organic compound. For example, when glucose first enters a cell, a phosphate group is transferred from ATP, forming glucose phosphate (C₆H₁₂O₆—P) and ADP. Once glucose is phosphorylated in this way, it can be stored as glycogen or metabolized for immediate energy.