Chemistry: Biochemistry: The Chemistry of Life

Introduction

Biochemistry is the study of the basic molecules used by living things. Nucleic acids, proteins, lipids (fats), and carbohydrates all perform specific functions within and between cells that allow organisms to survive. Biochemists seek to understand how these substances are formed, what purposes they serve, and how they might be used elsewhere to make medicines or other products.

Biochemistry analyzes the structure and physical properties of biomolecules (those produced by living things) and the systems in which they are used. Many biochemists study a particular class of biomolecule such as pigment-producing compounds or molecules that form membranes and structure within cells. Other areas of study include the many chemicals of cellular energy pathways, hormones, and other regulatory molecules, the synthesis of proteins, and the makeup and function of DNA.

Historical Background and Scientific Foundations

Before the early nineteenth century, most chemists accepted the idea that only living organisms could produce biomolecules. Louis Pasteur popularized the principle of vitalism—the theory that some “vital force” present in living things was necessary to make biochemicals. However, in 1828 the German chemist Friedrich Wöhler (1800–1882) accidentally produced the biomolecule urea, a waste product of human metabolism, from the reaction of two different mineral compounds. This proved that the chemical processes within living beings could be understood within the same rules of the larger field of chemistry.

Much of the earliest work in biochemistry dealt with the fermentation of sugar into alcohol. Before yeast was recognized as a living organism, different researchers argued about its role in the process. Some thought it was totally uninvolved, others thought it was merely a catalyst—an agent that causes a chemical reaction but is not involved in the process itself. When Pasteur proved that natural fermentation does not take place without the presence of yeast, many scientists sought to determine how this happens. It was Eduard Buchner (1860–1917), a German chemist who proved that living yeast is not necessary to ferment sugar, but only the enzymes from within the yeast cells, a breakthrough for which he won the 1907 Nobel Prize in chemistry. This seemingly simple discovery led others to investigate the properties of enzymes and other proteins, eventually revealing the structures of these molecules.

Today, most biochemists accept the idea that the first biomolecules formed before any life was even present. In 1953 American chemists Stanley L. Miller (1930–2007) and Harold C. Urey (1893–1981) performed their famous experiment that showed that the chemical and weather conditions of the very young Earth could have produced organic biomolecules from nonliving mineral sources. Starting with water, methane, ammonia, and hydrogen, they added heat and electricity and allowed the experiment to circulate for several days. After a week, some of the simple compounds had formed amino acids, sugars, and lipids. Many of these biochemical units are able to combine to form more complex biopolymers, which could lead to the development of RNA, the genetic code of simple organisms. In other words, the first living things arose from nonliving molecules that now are known as what make up the basic units of life. It should be noted that no one has yet created living cells from an experiment of this type, but much research continues in this area.

The modern study of biochemistry centers around the isolation of new biomolecules from living organisms, learning about their structure and properties, understanding the complex cellular cycles and pathways in which they are used, and developing new uses for them. The four major types of molecules studied by biochemists are carbohydrates, lipids, proteins, and nucleic acids.

Some biomolecules are hybrids of these major classes or their components (e.g., high-density lipoproteins or HDL are hybrids of lipids and proteins, while chondroitin sulfate, a component of cartilage tissue and arthropod exoskeletons, is an amino-sugar chain). Each of these categories is very large, containing a vast number of very different biomolecules. Because of this great diversity, many biochemists specialize in a much smaller class of molecules, or even one particular molecule. Others might work to create better experimental methods or apply others' discoveries in new ways.

Proteins

Many biochemists consider proteins the most important substances for study because they perform amazingly diverse tasks. For example, enzymes, the subject of so much early research, are proteins. Living things depend on enzymes to catalyze, or stimulate, important reactions that would not occur in their absence. Other proteins transport important materials around the cell or body, or store these materials for later consumption. Antibodies are specialized proteins produced by the immune system in response to a specific pathogen. They bind to disease-causing agents within the body, allowing immune system cells to recognize and destroy harmful intruders. Proteins perform many other functions within the body.

Most proteins are large, intricate molecules with chain-like structures that fold into a specific shape. Individual sections of the chain are made up of component amino acids. Though there are many kinds of amino acids, only 20 are used by all living things to produce thousands of different proteins. Biochemists have created several new amino acids that do not occur in any living organisms and have found important uses for them in industrial products.

Carbohydrates

Carbohydrates, the largest group of biomolecules, are dietary fuel—this is one of their major uses in living organisms. The most basic carbohydrates are monosaccharides, small simple sugar molecules. The most important of these is glucose, the body's major source of metabolic energy. More complex carbohydrates are used for longer-term storage of energy within the body, particularly in plants. These polysaccharides are also known as starches.

Very large carbohydrate molecules are usually not digested by humans, but still serve important tasks in many organisms. Cellulose gives structure to plants; it is the major component of wood and paper. Chitin, a glucose-based polymer, forms the exoskeleton in insects. Glycoproteins, or carbohydrates attached to amino acids, have important functions in the immune system and for blood clotting.

Lipids

Lipids are an important, although difficult to define, group of biochemicals. They are most commonly categorized as fats, but lipids include fats, oils, waxes, certain vitamins, some hormones, components of some cell membranes, steroids, fatty acids, and other related biomolecules. Until 1979 only two functions of lipids were known: energy storage and components of cell membranes. Then the lipid now known as platelet-activating factor was shown to help activate or mediate many immune responses. Following this discovery, other lipids were found to have important functions in sending signals within and between cells and transporting energy throughout the body.

Fatty acids are a class of lipids that are particularly important to human health. The body can produce most fatty acids, but those that must be consumed in the diet are called “essential fatty acids.” Maintaining the correct balance between omega-3 and omega-6 fatty acids may help reduce the risk of cardiovascular disease such as high cholesterol, high blood pressure, heart attack, and stroke. Other studies have suggested that fatty acids might have a positive influence on many diseases such as diabetes, arthritis, and several types of cancer.

Nucleic Acids

Nucleic acids are most often associated with the large, important molecules they can form by joining together: DNA and RNA. However, nucleic acids have other

important functions within the cell. They make up parts of coenzymes (molecules that carry material between enzymes), mediate and control various reactions, and store energy. When nucleic acids join with other base chemicals in a long chain, they form DNA or RNA. The specific sequence they form carries genetic information capable of replicating itself. DNA is often thought of as a set of instructions for making an organism. All of the necessary instructions are encoded in the way that the nucleic acids line up.

Cellular Respiration

Though many biochemists still study individual molecules, one of the most important features of modern biochemistry is the study of biochemical systems within the body or individual cells. Biochemical reactions often occur in a series, with the product of one step being used as material for the next. Many of these reactions are part of a cell's metabolism, which is vital for sustaining life.

Cellular respiration is the process by which cells obtain fuel, release its energy, and remove waste products. Almost all aerobic (oxygen-using) organisms, from yeast to humans, use the same reactions to fuel their life processes. One of these important reactions is glycolysis, which occurs in both plant and animal cells. Glycolysis transforms glucose, a relatively simple carbohydrate, into a molecule called pyruvate and a small amount of adenosine triphosphate (ATP), a high-energy molecule used by cells. Because this pathway is used by so many different kinds of life, it is considered one of the most ancient; it was probably present in a very distant common ancestor of most living things.

In aerobic cells, a process known as the citric acid cycle or the Krebs cycle uses the pyruvate from glycolysis to produce more energy. It is the final system that changes lipids, carbohydrates, and fatty acids into energy for the cell. There are eight steps in the citric acid cycle, each providing products that are used in the next step. The final step provides a molecule that contains the right amount of carbon to start the cycle all over again. Enzymes within a cell's mitochondria catalyze each step, allowing the release of more energy. The citric acid cycle also produces molecules that are the raw material for a number of other biochemical processes.

Plant cells use biochemical systems to generate energy, too. Many plants generate their energy from the sun, a process known as photosynthesis. This complex biochemical system produces chemical energy from photons, the subatomic particles that make up light.

Modern Cultural Connections

Much of this increased knowledge about biochemicals and biochemical systems has been put to use in the field of medicine. Because enzymes are well understood, specific blood tests have been developed to detect abnormal enzyme levels that indicate disease. Liver enzyme tests

can determine how well the liver is working or how far liver disease may have progressed. Cardiac enzyme tests can confirm whether a patient has had a heart attack and how severe it might have been. Drug developers use biochemical research to design compounds that address the specific causes of diseases, rather than blindly searching vast numbers of chemicals for one that works.

As our knowledge of biochemistry has increased, doctors and researchers have become more able to address the causes of disease rather than simply treating the symptoms. Research continues into more obscure and complex biochemicals, yielding new medicines, antioxidants, and antibiotics. The ability to understand and develop these new molecules grew directly from the understanding of the most basic biomolecules. Recognizing that the chemistry of life can be studied objectively has led to the science of biochemistry as we recognize it today.

Primary Source Connection

In 2006, a blood doping scandal in cycling known as Operación Puerto (Operation Mountain Pass) became public, disqualifying several well-known cyclists before the start of the Tour de France. Investigators located a lab in Spain and a doctor who was providing cyclists with banned substances and stocking blood samples from several riders.

That same summer, American cyclist Floyd Landis staged one of the most impressive come-from-behind victories in the history of cycling to win the Tour de France. Cycling officials charged Landis of doping after Tour officials asserted that one of Landis's blood sample—taken after the tough mountain stage where he regained the lead—tested positive for high levels of testosterone.

As of May 2007, blood doping scandals continue to mar professional cycling. Operación Puerto implicated several of the top riders in the sport, forcing some into early retirement. Prominent riders were once again caught doping during the 2007 Tour de France, and former Tour champion Landis was stripped of his win after being found guilty of using banned performance enhancing substances. Several riders face legal prosecution in their home countries or the possibility of being stripped of past victories.

While blood doping has become a problem in many sports, professional cycling has garnered much of the spotlight for doping scandals in recent years. As tests for various doping products have become better, more accurate, and more thorough, more riders are being caught blood doping and using illegal performance-enhancing substances.

The following article about the doping scandals was written by Jerome Pugmire, a sports writer for the Associated Press.

TOUR DE FRANCE FACES LONG RIDE BACK AFTER DOPING SCANDALS

PARIS (AP)—Cyclists who have admitted using banned drugs say the Tour de France may need years to recover from the stigma of cheating, denial and lying that devastated the 2007 race.

[2006's] Tour was bad enough, with Floyd Landis' positive test coming days after the race. This time, doping rocked the 104-year-old institution to its core.

“I thought this year would have been better,” former rider Frankie Andreu said. “Obviously it wasn't. So I'm not confident that even next year will be better.”

French Sports Minister Roselyne Bachelot promised on Monday that the 2008 Tour will be “clean and renovated,” likely with tougher doping sanctions, unannounced hotel room searches and other measures.

Patrice Clerc, head of Amaury Sport Organization that organizes the Tour, said next year's race will be the first step in rebuilding high-level cycling.

“The 2008 Tour will not be like the 2007 Tour,” Clerc said. “I commit myself to that.”

This time, fan favorite Alexandre Vinokourov, race leader Michael Rasmussen and Italian rider Cristian Moreni were all cited for doping or, in Rasmussen's case, for lying about his whereabouts while skipping tests.

German rider Patrik Sinkewitz also tested positive, except his test was from before the race and revealed during it.

“It's going to take five and 10 years until we have faith in the riders,” Britain's David Millar said. “That's such a shame for the younger guys who are coming through and deserve it now because they're getting put in the same bracket.”

Cynicism among some fans was clear.

“Tour of Transfusion,” read one roadside banner.

Many now look to the new guard of young riders to stand up against doping. But will 24-year-olds like Tour winner Alberto Contador, Linus Gerdemann and Markus Fothen speak their minds?

Gerdemann, who won an Alpine stage on July 14, already has.

“We have to go that way, otherwise cycling is dead,” Gerdemann said. “Everyone has to understand that this is the new way, and there are no other possibilities.”

That won the approval of Millar, who like Andreu, used the performance enhancer EPO.

“It's going to take awhile to earn the trust,” Andreu told The Associated Press.

After Sinkewitz's positive test for testosterone, two German television stations ended their coverage.

“It's important that riders have an opinion and say it,” Fothen said. “So much silence. In the past was a generation that did things that were not good. Now we are a new generation. I can speak loud.”

Andreu, a former teammate of seven-time Tour winner Lance Armstrong, wants Fothen to keep talking.

“It could be a generational thing because the guys grew up racing in the ‘90s fell into maybe taking stuff in order to perform,” said Andreu, who admitted taking EPO in 1999.

Credit Agricole sporting director Roger Legeay says it will take more than youth.

“In 1998 they said we'd see a new generation,” Legeay said. “In 2004 we'd see a new generation … so history repeats itself. Today we really have all the means at our disposal. Urine tests, medical records, DNA, random tests.”

After clinching his Tour title at Saturday's time trial, Contador said he would take a DNA test, but only if asked.

“I'm innocent and I don't have to prove anything to anyone,” Contador said. “Who should I have give my blood to? You?”

Contador never tested positive and there is no evidence tying him to blood-doping. Yet the fact he had to face questions reflects the current climate of suspicion.

One rider at this race, Germany's Erik Zabel, previously admitted taking EPO in 1996. Unlike Millar and Andreu, he has said hardly anything about doping.

“I said to him that we talk about it, that we should do an interview together,” Millar said. “He's got to talk more about it. We can't just admit it and bury it.”

The old guard like Zabel will soon be gone. Vinokourov and Landis may yet never ride the Tour again.

Millar accepts that fans may not start believing any time soon.

“They have every right not to,” Millar said. “We expect a lot of our grand champions, and even when they do make mistakes, they don't face up to them. It's unfortunate, it's kind of a tragic twist.”

Andreu remembers clearly the pressures to use banned drugs.

“You always wondered what the next guy was doing,” Andreu said. “If you're trying to win the Tour de France and you think everybody else is doing stuff it becomes an arms race. And it might be a mysterious arms race because you never know, but you don't want to be caught out. So it becomes a game.”

Jerome Pugmire

pugmire, jerome. “tour de france faces long ride back after doping scandals.” associated press newswire (july 30, 2007).

See Also Biology: Cell Biology; Biology: Genetics, DNA, and the Genetic Code; Biology: Sociobiology; Chemistry: Organic Chemistry.

bibliography

Books

Berg, Jeremy M., John L. Tymoczko, and Lubert Stryer. Biochemistry. 5th ed. New York: W.H. Freeman, 2001.

Periodicals

Miller, Stanley L. “Production of Amino Acids under Possible Primitive Earth Conditions.” Science 117 (May 15, 1953).

Pugmire, Jerome. “Tour de France Faces Long Ride Back after Doping Scandals.” Associated Press Newswire (July 30, 2007).

Web Sites

Indiana State University School of Medicine. “Biochemistry of Nucleic Acids.” http://www.indstate.edu/thcme/mwking/nucleic-acids.html (accessed January 24, 2008).

Lipid Library. “About Lipids.” December 15, 2007. http://www.lipidlibrary.co.uk/lipids.html (accessed January 24, 2008).

Nobel Foundation. “Cell-Free Fermentation.” http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1907/buchner-lecture.pdf (accessed January 24, 2008).

United States National Library of Medicine. National Institutes of Health. MedLine Plus. “Carbohydrates.” January 22, 2008. http://www.nlm.nih.gov/medlineplus/carbohydrates.html (accessed January 24, 2008).

University of Akron. Department of Chemistry. “Carbohydrates.” http://ull.chemistry.uakron.edu/genobc/Chapter_17/ (accessed January 24, 2008).

University of Maryland Medical Center. “Omega-3 Fatty Acids.” May 1, 2007. http://www.umm.edu/altmed/articles/omega-3-000316.htm#Uses (accessed January 24, 2008).

University of Texas Institute for Cellular and Molecular Biology “Glycolysis.” July 18, 1998. http://biotech.icmb.utexas.edu/glycolysis/glycohome.html (accessed January 24, 2008).

Kenneth T. LaPensee