Olestra
Nat Cooper

Chemical Concepts

Micro/Macro
and Symbolic
Representation

Structural formulas and various space-filling models help us visualize molecules. 

Proteins: Proteins play important roles in nearly every biological process. Looking at our bodies as machines, proteins form all of the muscles, skin, bone, and connective tissues, which help us move. Nearly all of the chemical reactions in our bodies, from the simple to the complex, are accelerated by the presence of biological catalysts, made from protein macromolecules, known as enzymes. Proteins store and transport many small molecules and ions; the iron and oxygen that we depend on change hands from protein to protein. Hemoglobin and Myoglobin transport oxygen first in the blood, then in the muscles. Transferrin and Ferritin carry iron in the blood and then store it in the liver. Proteins provide immune protection. The antibodies that recognize and combine with viruses, bacteria, and foreign cells are highly specific proteins. Proteins also generate and transmit nerve impulses. Rhodopsin, a protein photoreceptor, changes in response to the light that enters our retina. Other receptor proteins control nerve impulse transmission and the synapses or junctions between nerve cells.

Proteins control growth and differentiation at many levels. At the cellular level, repressor proteins silence specific portions of DNA to help control these growth and differentiation processes. Hormones, such as insulin, human growth hormone and those that control thyroid stimulation are all proteins that control the flow of both matter and energy in our intricate bodily systems.

Proteins are very large molecules that are made from long chains of relatively simple
molecules known as amino acids.  

The structure of these macromolecules can be described on four levels; primary, secondary, tertiary, and quaternary. The primary structure describes the amino acid sequence that forms the long chain known as the polypeptide chain(s). This is accomplished when single amino acids form a peptide bond by a condensation reactionn that occurs at the alpha carboxyl (COOH) end of one amino acid and the alpha amino (NH₃) end of another amino acid. You can see models of the simple peptides formed by condensation using your Chime download.  Multiple condensation reactions lead to macromolecules - molecules with long chains of atoms.

A very important advancement in the growth of the field of chemistry was intertwined with the determination of protein secondary structures. Chemistry, prior to this discovery, had largely been phenomenon based. Various chemical phenomenon were associated with certain conditions, but the predictive powers of chemistry were limited. The nature of the chemical bond was gradually giving up its secrets, in part due to the pioneer work of Linus Pauling, and his associate, Robert Corey. They were doing detailed X-ray crystallographic studies on the peptide bond. After many years of trying to tackle the possible shapes that the peptide chains could assume, Linus Pauling finally solved part of the puzzle. He was in bed, sick with the flu, when he worked out a possible shape while using long sheets of paper with the molecules accurately drawn on them. This first shaped was named the alpha helix and Pauling and Corey also discovered, in the same year, a second structure, the beta pleated sheet. The prediction of these two structures, some six years prior to their actual experimental confirmation, was a landmark discovery because it demonstrated that the secondary (3-d) structure could be determined if the primary structure was precisely known. This represented a huge leap in the predictive powers of chemistry, and Linus Pauling was awarded a Nobel Prize for his work on the nature of the chemical bond.

The tertiary structure in a protein is similar to the secondary structure, in that it also describes three-dimensional structure, but the tertiary structure describes the spatial locations of the polypeptide chain as it folds, loops, or turns around itself, rather than the 3-d nature of the chain itself. The different properties that result from the secondary and tertiary structure can be seen in natural macromolecules like the protein silk.

ß-Sheet Tertiary Structure of Silkworm Silk: "Wireframe model" 
See how the long protein molecules stretching across the image lie parallel into an orderly pattern.  Separate chains of proteins are held in place by interchain hydrogen bonds.  Think of how this microscopic structure is exhibited in the macroscopic properties of the fiber, silk.

Almost all proteins are made up of more than one polypeptide chain. This accommodates the different functions and facilitates the synthesis of these proteins more readily. These different peptide chains are called subunits and the spatial arrangement of these subunits gives rise to the quaternary structure of a protein. An example of this is shown by Hemoglobin, which is a globular protein made of four subunits (two alpha chains and two beta chains).

As mentioned previously, proteins can accelerate the numerous chemical reactions that occur in our bodies. They accomplish this by acting as biological catalysts or enzymes which are present by the thousands in our cells. Recall that a catalyst is something that accelerates a reaction without actually being consumed by the reaction. An ordinary catalyst acts by lowering the activation energy of a particular reaction pathway. The role of an enzyme or series of enzymes, while similar in terms of lowering the activation or transition state energy, is far more efficient and specific. To begin our exploration of the details of enzymes, lets look at a few examples.

Have you ever put household hydrogen peroxide on a cut or scrape? It bubbles and fizzes, doesn’t it. If you apply it to undamaged skin you will also notice the absence of this effervescence. Hydrogen peroxide naturally decomposes over time to produce water and molecular oxygen according to the reaction:

2H₂O_{2 ->}2H₂O + O₂

When we apply it on a cut, it bubbles because our blood contains catalase, a protein enzyme that accelerates the above reaction. The hydrogen peroxide is useful on the wound for two reasons: the fizzing of the oxygen bubbles helps to mechanically clean the wound and the hydrogen peroxide destroys the cell membranes of any bacteria present, partly due to the fact that the bacterium do not contain this enzyme, catalase.

Have you eaten a cracker recently? The starch that is in that cracker and most of the carbohydrates that we readily consume is immediately attacked by the enzymes in our saliva and later in our intestines. The enzyme, alpha amylase, initially breaks down (by hydrolysis) the starch polysaccharide into maltose, maltotriose and alpha dextrin. These sugars, maltose (a disaccharide) and maltotriose (a trisaccharide), are then further broken down in the small intestine by the enzyme maltose to produce the glucose that is absorbed into our blood. Other enzymes break down the remaining sugars, including the enzyme lactase, which breaks down the milk sugar lactose. While nearly all infants and children produce lactase and readily digest milk, many adults, including a majority of some adult populations, do not produce this important enzyme, and are lactose intolerant.

The forces that bind a reactant or substrate to an enzyme are the same that give shape to the enzyme proteins including Van derWahls, electrostatic, hydrogen bonding, and hydrophobic interactions (see your text for a review of these forces). These forces, while quite small compared to the covalent bonds that form the amino acids and polypeptide chains, lead to the many remarkable properties of enzymes. Enzymes typically accelerate reactions by factors ranging from a million to 100 billion times faster than the same, uncatalyzed, reaction. These reactions also occur under relatively mild conditions: physiologic temperatures (< 100^oC), near atmospheric pressures, and close to neutral pH’s. Chemical catalysis typically occurs under more extreme temperatures, pressures and pH’s. Enzymes, because of these delicate forces and intricately folded shapes, can be highly specific and self-regulating.

Models that explain enzyme behavior contain several key elements. The catalytic ability of enzymes comes from creating specific geometries that orient the substrate molecules in a particular manner. This occurs when the enzyme and substrate bind together forming an enzyme-substrate complex. This place, where the binding of the substrate occurs, is known as the active site of the enzyme. The active sites involve only a few amino acid residues out of the more than 100 amino acids in a typical enzyme. These few amino acids, often from several locations along the polypeptide chain, form a three-dimensional cleft or crevice, into which the substrate fits. In 1894, Emil Fisher discovered that glycolytic (sugar breaking) enzymes recognize different shaped (stereoisomeric) sugars. This led to the lock-and-key hypothesis where the lock is the active site and the key is the substrate.  Further discoveries found that many enzymes change shape upon substrate binding leading to an alternate hypothesis called the induced-fit model. Both of these models help explain how enzymes can display a high, in some cases absolute, degree of specificity for substrate binding.

The harmful effect of poisons and various toxins are often related to enzyme action.  In some cases an enzyme will produce a lethal product when a similar but unwanted substrate is ingested. This occurs if someone accidentally ingests ethylene glycol (antifreeze) or methanol (wood alcohol). A treatment for this is to administer a large (intoxicating) dose of ethanol that acts as a competing substrate, thus preventing the unwanted reaction. Other toxins such as the arsenic of Arsenic and Old Lace act to block the active site, thus preventing a desired reaction. Some poisons can attach to the enzyme and change its overall shape and render the active site useless. In our walking, talking, chemical factories, there is a delicate balance among the myriad of constantly occurring reactions, that leads to the health that most of us enjoy, and the illness that some encounter.

A specific class of enzymes that is pertinent to our Olestra Chemcase is lipases, which break down lipids or fats. While there are many types of lipases, the type we will later focus on are the triacylglyceride lipases that break down the typical dietary fats, triglycerides. Lipases of interest come from three sources: lingual (secreted by the tongue), pancreatic, and various lipases that occur in our food. There are currently numerous interesting fronts of research on lipases. The dairy industry uses lipases to modify the fatty acid chain lengths, thus modifying the flavors of various cheeses. Research to develop household cleaners that use lipases to bust those dreaded grease molecules is ongoing. In the oleochemical industry, lipases are being developed that can perform the required hydrolysis, glycerolysis and alcoholysis reactions without the extreme temperature and pressure conditions that accompany traditional industrial processes. Lipases are used to convert the cheaper, less desirable palm oils into more expensive cocoa butter. Medical applications are being considered for possibly developing lipase inhibitors, as a possible treatment for obesity, and we will revisit this dietary role later on as we look at the development of Olestra. For now though, lets return to the Olestra concept map and look at the other types of food molecules.