CHEMICALS IN HEALTH SCIENCE

bi•o•chem•is•try (bi ´ o kem ´ is tree):

n., the chemistry of living organisms.

Simply stated, biochemistry is life. Practically stated, biochemistry is our life: what we are and how we live. Our bodies are very busy factories, extracting energy from the foods we eat, building cells and tissues, and knitting everything together into a functioning unit using molecular tools called enzymes. Creatures as distinct as bacteria, giraffes, and people use many of the same biochemical toolsets to survive, eat, move, and interact with their respective environments. Biochemistry underlies our health.

Health science is the applied science dealing with health, and it includes many sub disciplines.
There are two approaches to health science: the study and research of the human body and health-related issues to understand how humans (and animals) function, and the application of that knowledge to improve health and to prevent and cure diseases.
Health research builds upon the basic sciences of biology, chemistry, and physics as well as a variety of multidisciplinary fields (for example medical sociology). Some of the other primarily research-oriented fields that make exceptionally significant contributions to health science are alternative health, biochemistry, epidemiology, and genetics, natural health.
Applied health sciences also endeavor to better understand health, but in addition they try to directly improve the health of individuals and of people in general. Some of these are: alternative health, biomedical engineering, biotechnology, nursing, nutrition, pharmacology, pharmacy, public health, psychology, physical therapy, and medicine. The provision of services to improve people's health is referred to as health care.
The health sciences industry, a multi-billion dollar business sector, is a cross-section of the life sciences and the health care and medical diagnostics industries.

In health and in disease, our bodies are biochemical laboratories abuzz with activity, where molecules are constantly being made, used, broken down, and recycled. What does the lion's share of the work? Indispensable molecules called enzymes.
When routine blood tests reveal abnormally high liver enzyme levels, for instance, there are many potential causes, depending on which enzyme levels are awry and how off-kilter the levels are. The culprit could be as serious as alcoholism or infection with one of the hepatitis viruses, both of which can cripple the liver over time. Or the cause could be as innocuous as taking certain common medicines or having a few extra drinks at a party.
Many of the body's enzymes reside inside cells. If cells are damaged, they break apart and spill their contents into neighboring body fluids, like blood. The presence of higher-than-normal levels of enzymes in the blood can signify trouble in the tissues or organs (such as the liver) that those cells normally populate. But sometimes, abnormal lab results mean nothing at all. Elevated enzyme levels caused by the body's processing of "toxins"—including substances like chemicals in the environment, prescribed medicines, or alcohol—usually return to normal once the foreign substance is gone from the scene.
The liver is not the only place enzymes hang out. Every cell in every organ—from the liver to the heart to the skin—is chock full of enzymes. Anything but innocent bystanders, enzymes are the reason why cells are bustling centers of activity.
Enzymes underlie our ability to move, to think, to sense our world. Enzymes help us wink an eye, savor an ice cream cone, and catch a sticky drip about to fall off the edge of the cone. Enzymes, and their essential cellular associates—other proteins, nucleotides, sugars, and fats—allow a stubbed toe to heal properly and nurture a fetus growing inside a woman's body.
But when they are not working properly, enzymes can cause disease. Cancer can happen when the enzymes that copy the genetic material DNA make mistakes, giving rise to an errant gene that produces a faulty protein, or no protein at all. If that particular protein is the one that keeps a given set of cells from multiplying out of control, then its absence can bring about dire consequences.
Although a scientist may study a couple of isolated enzymes in the laboratory, inside the body enzymes are never lonely. They link up to form vibrant networks and pathways. The study of biochemical pathways and networks, and how they reverberate and influence each other, is the science of life and the chemistry of health.

Chapter 1: Actions and Reactions

Even though you're probably sitting down while you're reading this, your body is anything but static. Thousands of enzymes in your body toil away every second of every day, breaking apart the components of the foods you eat into energy for essential life processes. Vision, movement, memory—you name it, there are enzymes at work behind the scenes.
Enzymes work by making it possible for chemical reactions inside your body to take place. While that might not seem significant, consider the fact that without the help of enzymes, the conversion of nutrients and minerals into usable biological molecules such as proteins and nucleic acids might take weeks, even years. Enzymes can make this happen in minutes, sometimes seconds.

Cascades of enzymes make up metabolism.

How do they do it all, and so well? Enzymes act like the accelerator pedal of a car. But they also play the role of matchmaker, bringing together starting materials and converting them into finished materials (called reaction products). One secret to an enzyme's success in this endeavor is its shape. An enzyme is shaped so that it can hug its substrate tightly. This molecular embrace triggers chemical changes, shuffling chemical attractive forces called bonds and producing new molecules. Only enzymes that have an exact fit with their substrates do a decent job of speeding up chemical reactions. But things don't end there; reactions are not singular events. They re-occur, over and over again. Enzymes are the key players linking up chain reactions of the chemical events that culminate in our everyday physiology. Much like a cascade of dominoes, the product of one chemical reaction becomes the substrate for another. Enzymes form the core of these ordered pathways, which themselves are the basis for metabolism. In a grand sense, metabolism is the process any organism uses to retrieve energy from Product the environment and use it to grow. The proper functioning of small and big body parts hinges upon effective communication within and between pathways. That includes everything from tiny specks of DNA that string together into all of your genes to a complicated, multicelled organ such as the heart. By understanding the language of physiological communication systems, scientists can devise ways to patch the circuits when they become broken, in illness and disease.

Chemical Biology in Action: Just Say NO

Protein crystals of nitric oxide synthase revealed its three-dimensional structure.
T.L. POULOS, H. LI, C.S. RAMAN

The molecule that manufactures NO is an enzyme called nitric oxide synthase (NOS). Owing to nitric oxide's many different functions in the body, three different versions of NOS exist, specialized for the cardiovascular, immune, and nervous systems. In recent years, scientists have achieved a major victory in beginning to understand how NOS works. Thomas Poulos of the University of California, Irvine, determined the structure, or three-dimensional shape, of one form of NOS. Since intimate associations between an enzyme and its substrate rely on a snug fit, probing the three-dimensional shape of an enzyme or other protein can enable scientists to begin to understand how the protein works, predict what other molecules it might fit, and design drugs to boost or block its activity. After obtaining a sample of NOS protein from the laboratory of Bettie Sue Masters of the University of Texas Health Science Center at San Antonio, Poulos obtained a "picture" of NOS by bombarding a tiny crystal arrangement of the protein with high-energy X rays, then piecing together the protein's shape by tracing the directions in which the energy was scattered throughout the crystal. This work, years in the making, paints a portrait of NOS consisting of two identical units. In a cell, the two units of NOS assemble head-to-head, creating a new landscape upon which substrates and helper molecules convene to complete the task at hand: creating nitric oxide from an amino acid called arginine. In the case of NOS, the helpers include iron and a tiny molecule called a cofactor. Enzymes like NOS are lost without these helpers.

  

Folic Acid Saves the Day

In baking, some ingredients are simply not optional—forget the baking powder, forget the muffins. Just as baking powder is essential for some recipes, helper molecules called cofactors are necessary ingredients for many biochemical reactions.
Take folic acid (one of the B vitamins), for example. Scientists have known for decades that folic acid can protect against certain birth defects—such as spina bifida—that develop during the first few weeks after conception. For this reason, the Food and Drug Administration recommends that every woman of child-bearing age supplement her diet with 400 micrograms of the vitamin. Scientists figured out that folic acid does its molecular good deeds by lowering levels of a potentially harmful compound called homocysteine, which is also a risk factor for heart attacks and strokes. As it turns out, folic acid performs this task by speeding up the conversion of homocysteine to methionine, a nontoxic amino acid that the body needs.
Folic acid does this by improving the fit between an enzyme and its cofactor. The enzyme in this case is known shorthand as MTHFR, and the cofactor, a molecule called FAD, is also vitamin-derived (from vitamin B2) and is essential for converting homocysteine to methionine. Martha Ludwig and Rowena Matthews, both of the University of Michigan Medical School in Ann Arbor, determined that by locking FAD onto MTHFR, folic acid performs this protective role in the body

Pulling Into Dock

Like a ship nestling into its berth, many proteins require the help of one or more other proteins to perform their jobs well. However, unlike ships, proteins docked together often change their shape as a result of such an encounter. The differently shaped protein is newly and exquisitely able to capture a substrate and carry out a chemical reaction. Akin to rearranging seats in a room to accommodate more guests, the reshaping of proteins (called conformational changes) can make extra room for substrates and products to fit. Such shape changes also change the electrical "ambience" of an enzyme's innards, revealing differently charged portions of the molecule that can have a big impact on molecular interactions.

 

 

 

Making a Protein From Scratch

Tucked away inside the DNA sequence of all of your genes are the instructions for how to construct a unique individual. Our genetic identity is "coded" in the sense that four building blocks, called nucleotides, string together to spell out a biochemical message—the manufacturing instructions for a protein. DNA's four nucleotides, abbreviated A, T, G, and C, can only match up in specific pairs: A links to T and G links to C. An intermediate in this process, called mRNA (messenger ribonucleic acid), is made from the DNA template and serves as a link to molecular machines called ribosomes. Inside every cell, ribosomes read mRNA sequences and hook together protein building blocks called amino acids in the order specified by the code: Groups of three nucleotides in mRNA code for each of 20 amino acids. Connector molecules called tRNA  aid in this process. Ultimately, the string of amino acids folds upon itself, adopting the unique shape that is the signature of that particular protein.

A Special Bond

Three types of attractive forces hold atoms together to make molecules. Dots represent electrons taking part in chemical bonding.

You may be surprised to learn that at the heart of chemistry is physics—the study of attracting and repelling forces that link up the building blocks of life. Chemical bonds are those physical forces that keep atoms together, and they come in a few varieties (see drawing/illustration at right). Ionic bonds, in which positively charged atoms are attracted to negatively charged atoms, are the strongest of the bond types. Covalent bonds are more subtle, and occur when neighboring atoms (such as hydrogen) share electrons from within their respective halos of swirling particles. Chemists refer to both ionic and covalent bonds as "intra-molecular" forces. Other important forces are called "inter-molecular" forces—those holding different molecules together. These types of forces form the basis for liquids and solids, which are really just collections of molecules arranged in a precise pattern in space. Intermolecular forces are also called van der Waals forces, named for the Dutch physicist who first discovered them. Hydrogen bonds are a type of van der Waals force, and represent an important bond in biochemistry. A Killer's Strategy

Drug-sensitive bacteria are killed when vancomycin attaches to an Alanine-Alanine strand of the bacterium's growing cell wall (top), preventing the protective cell wall from forming at all. Vancomycin cannot attach to the slightly different, Alanine- Lactate strand of the drug-resistant bacteria (bottom). As a result, the resistant bacteria are able to make their tough cell wall and survive in the presence of the antibiotic drug.

A type of bacteria called enterococci possess enzymes that weave together alternating protein-sugar strands to create a tough cell wall—the bacteria's main defense against the outside world. The antibiotic drug vancomycin interferes with production of the cell wall (see drawing/illustration at left). This kills the bacteria, which stops infection. Some bacteria become resistant to vancomycin, and thrive in the presence of the antibiotic. The developing cell wall of vancomycin-resistant bacteria has a slightly different composition that the drug molecule does not recognize. Specialized resistance genes provide the resistant bacteria with the ability to reprogram the composition of the cell wall.

 

Chemical Biology in Action: Chemistry to the Rescue

Arguably many of the most important medical advances this century relate to the development of powerful antibiotics and vaccines to treat infectious diseases caused by bacteria, viruses, and parasites. But those breakthroughs have come with a cost—the microbes have learned how to fight back, and with a vengeance. The misuse of antibiotics—these drugs are over-prescribed by doctors and people often fail to finish a full prescription—is the most common reason why antibiotic resistance is coming so rapidly to the fore.
When you take an antibiotic, the drug treats infection by knocking out hundreds of strains of "sensitive" bacteria in your body. But it also leaves behind scores of "resistant" strains—slightly altered versions of the sensitive variety. The resistant microbes, with no stops in place, repopulate themselves rapidly. To make matters worse, these lingering resistant organisms hang out not only in your body, but they can spread to your family and friends—worsening the problem for everyone.
Bacteria are not inherently malicious. In the human body, many different types of bacteria reside within the large intestine, where they perform vital roles in processing food. Trillions of microorganisms break down undigested carbohydrates, common components of vegetables and other foods like beans. In the wrong place, however, these normally innocuous bacteria—called enterococci—can do the body great harm. In disease, such microbes can seep from the relatively safe harbor of the intestines into other regions of the body, such as burned skin, the heart, or the urinary tract. There, the bacteria can multiply rampantly, especially when the immune system is already strained. Enterococci are stubbornly resistant to most antibiotic drugs. Until recently, an antibiotic called vancomycin fairly effectively put the brakes on enterococcal infections. However, in recent years the incidence of enterococcal resistance to vancomycin has been on a disturbing rise.
Fortunately, chemists are hot on the heels of enterococci. Christopher T.Walsh and Daniel Kahne, both of Harvard Medical School in Boston, Massachusetts, have traced the roots of vancomycin resistance to a single, errant chemical link. Vancomycin normally kills enterococci by getting in the bacterium's way while it tries to manufacture a protective cell wall for itself. Vancomycin prevents the molecular "bricks" of this cell wall from melding together, leaving the bacterium susceptible to the harsh environment and destructive enzymes in the cells of its host's body. Walsh, Kahne, and their coworkers unearthed a set of just five genes that enable enterococci to get past the antibiotic drug vancomycin's action by using a slightly different method to build a cell wall. The researchers' detective work points to on the strategy of interrupting enzymes that rearrange the cell wall precursors.