The Tour de France is the super bowl event of cycling.

Many suggest one of the most

exciting Tour de Frances in recent history occurred in the year 2006. Floyd Landis held a ten

second lead during stage 15 of the race. Stunningly, Landis watched this ten second lead turn

into an eight minute deficit the next day. However, when stage 17 commenced Landis silenced

the cycling world by transforming that eight minute deficit into a nine minute lead. Upon

establishing this lead Landis held on, and received the title. Unfortunately, this is only the tip of

the iceberg. A drug test came back positive for the performance enhancing drug testosterone.

The Tour de France committee took this evidence seriously, and stripped Floyd Landis of his

2006 title.

Performance-enhancing drugs are chemical substances that give an athlete an edge in

competition. These drugs can affect the body in many ways such as increase in muscle mass,

increase in the blood’s capacity to carry oxygen throughout the body, pain masking, weight

reduction, masking of other illegal substances, and stimulation of the body. Different types of

performance-enhancing drugs include steroids, creatine, human growth hormone, stimulants, and

diuretics. Although there are short term benefits, these drugs are considered to be medically

hazardous.

The majority of the time when an athlete gets busted for using performance-enhancing

drugs, the drug of choice is steroids. These substances are lipids, which imply that they have

hydrophilic heads and hydrophobic heads. Steroids are structurally very rigid. The have a cyclic

hydrocarbon backbone that can contain one to hundreds of hydrocarbon rings. Extending from

the cyclic rings are chains of hydrocarbons containing polar residues. Sometimes these polar

residues are attached directly to the cyclic backbone. The body natural produces many types of

steroids. Some of the steroids produced by the body are androgens, estrogens, glucocorticoids,

and mineralocorticoids.

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 Testosterone is a type of androgen that athletes put into their system to increase their

muscle mass. The effects on the human body from testosterone occur by means of two

mechanisms: androgen receptor activation and the conversion estradiol. Unbound testosterone is

first transported to the cytoplasm of the target cell. At the target cell, binding between

testosterone and the androgen receptor occur3. The testosterone-receptor complex than makes a

conformational change that allows it to pass through the cell’s cytoplasm. Once inside the cell

the complex binds to a specific nucleotide sequence in the DNA. The areas of binding are called

hormone response elements, and these influence the transcription of many genes. It’s important

to note that the free testosterone could have been reduced by 5-alpha reductase which would

have strengthened the bond between the testosterone-receptor complex2.

Testosterone has the rigid steroid structure. It has three six member ring structures and

one five memebred ring structure9. Some of the OH

effects testosterone has on the body is it causes

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a deepening of the voice, increase muscle mass,

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enhanced strength, and enhanced endurance. At O

high levels testosterone can have adverse effects on the body. One of the more serious effects is

that it induces apoptosis (self-destruction of the cells). This process is similar to the process of

Alzheimer’s disease.

A more general type of steroids that athletes take to increase muscle mass is anabolic

steroids10. Testosterone is actually a specific anabolic steroid. This results in the two having

similar structures and physiological effects. A little difference between the two occurs in the

mechanism of activation on muscle mass. Anabolic steroids cause an increase in proteins and

they also reduce the activity of cortisol on muscle tissue. Since muscles are made mostly of

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proteins this effect is very beneficial to the muscle, and it can increase its mass. Cortisol is

involved in the breakdown of muscle tissue. Since anabolic steroids also inhibit cortisol’s

activity another path is opened for increased muscle mass. It is also widely thought that

reduction in muscle breakdown may occur through anabolic steroids inhibiting the action of

other glucocorticoids which promote the breakdown of muscles.

Another type of performance-enhancing drug that athletes use is creatine. Naturally

produced in the kidneys and liver, creatine provides a fuel source for

muscles during intense exercise1. Creatine is formed from three amino

acids: glycine, arganine, and methionine. Creatine is synthesized in a

series of steps that require enzymes to catalyze them. The first step includes arginine and

glycine reacting together in the presence of arginineglycine amidinotransferase which produces

guanidinoacetic acid. The second step converts guanidinoacetic acid to creatine in the presence

of methionine and the enzyme GAMT. The first of these reactions occurs in the kidneys, and the

second reaction occurs in the lungs. The entire mechanism of creatine synthesis is shown below.

One of the side affects of creatine that athletes desire is increase weight gain. However,

after extended use weight gain is primarily due to an increase in water retention of the muscle

rather than an increase in muscle mass. This increase uptake of water by the muscle also

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dehydrates the body. Other possible negative side effects are stomach and muscle cramps,

nausea, vomiting, diarrhea, kidney damage, liver damage, and heart damage. Although there are

many negative side effects creatine is considered to be safe drug if taken in moderation by a

healthy individual.

Human growth hormone (HGH) is a peptide hormone that has a molecular weight of

22,124 daltons. The structure is composed of four helices which allow the growth hormone to

functionally interact with the GH receptor. The effects of HGH on the human body are very

similar to those observed in anabolic steroids. HGH increases the strength of an individual by

increasing that persons muscle mass. Other functions of HGH include growth stimulation in

children, increase protein synthesis, reduction of glucose uptake by liver, anti-age effects,

promotion of lipolysis, and stimulation of the immune system. Extended use of HGH can result

in thickening of the jaw, fingers, and toes. Also stemming from prolonged exposure of the

growth hormone HGH is increase nerve pressure, muscle weakness, reduced sexual function, and

in some cases diabetes.

Drugs that temporarily increase an individual’s alertness and awareness is known as a

stimulant. A few examples of stimulants include amphetamine,

NH 2
methylphenidate, and ephedra. The structure of amphetamine

consists of benzene ring with a two membered carbon chain

containing an amine7. Amphetamines increase concentration,

alterness, self-confidence, decreases appetite, and provides a sense of energy by acting on an

individual’s nervous system. However, this sense of energy the athlete feels is just an illusion.

The athlete’s judgment becomes distorted enough by the drug that he believes he is actually

performing better than he is in actuality. Short term effects of amphetamines include headaches,

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weight loss, hallucinations, heart rhythm abnormalities, heart attacks, and increased blood

pressure. Long term effects include uncontrollable movement of the face, nerve damage,

paranoid delusions, tremors, anxiety, irregular heartbeat, and insomnia.

Methylphenidate is a prescription stimulant to treat people with attention deficit

hyperactivity disorder8. Its main role is to increase a person’s ability to

O O
foucs on tasks. How exactly does the molecule achieve this effect?
H
Many postulate that methylphenidate causes a dopamine imbalance in N

the brain. This occurs because methylphenidate not only facilitates the

release of dopamine at the synapse, but it is also a dopamine receptor inhibitor. Without having

the ability to bind to the receptors dopamine is left unbound and free. Side effects of

methylphenidate include insomnia, mood changes, hallucinations, stomach aches, headaches,

diarrhea, and psychosis.

Ephedra is a plant that has been known for many years because of its biochemical effects

on the body. Its uses date back to as far as 2,000 years by the Chinese to

treat/cure asthma, hay fever, and the common cold11. The main two

substituents of ephedra are ephedrine and pseudoephedrine. These alkaloids

cross the blood-brain barrier and mimic the “flight or fight” response of the

central nervous system4. Once in the brain the molecule stimulates the release of norepinephrine

as well as α and β adrenergic receptors. The β-2 receptors provide positive results by opening

airways which allows air to enter the lungs. However, some receptors are activated that have

negative effects on the body. β-1 receptors increase the heart rate and force of contraction, and

the α-1 receptors increase blood pressure and decrease circulation to the renal system and other

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parts of the body. Side effects of ephedra include nausea, kidney stones, tremors, dry mouth,

dizziness, and increased urination.

A diuretic is a drug that increases the frequency of urination. This increase in urination

results in a large loss of water. By losing enough water (without being dehydrated) one becomes

lighter, which could be a desirable trait for an athlete. There are several types of diuretics, these

include high ceiling loop diuretics, low ceiling diuretics, thiazides, potassium-sparing diuretics,

and osmotic diuretics. All diuretics increase the rate of urination, but the only difference is the

way in which they accomplish this task. A major side effect of diuretics is dehydration

Two major instruments used to detect the presence of a performance enhancing drug in

the body are gas-liquid chromatography (GC) and mass spectroscopy. A gas chromatograph

separates chemicals in a complex sample. For any chromatographic technique two phases exist,

a mobile and stationary phase. The stationary phase in gas-liquid chromatography consists of a

nonvolatile liquid. The mobile phase is the liquid being injected into the instrument. Upon

injection of the mobile phase, the components vaporize and are carried into the column by the

carrier gas, where separation occurs. The compounds in the mobile phase partition themselves

between the gas and liquid phases, in an equilibrium that depends on temperature, the rate of gas

flow, and the solubility of the components in the liquid phase. The partitioning of a substance

between the liquid and gas phases depends on its attraction for the liquid phase and its vapor

pressure. Volatile compounds tend to spend most of the time in the gas phase. This results in

lower-boiling-point compounds traveling through a GC column faster than higher-boiling

compounds5.

Mass spectrometry is another technique used to detect performance-enhancing drugs.

Mass spectrometry involves energy transfer from energetic electrons. Ionization of molecules is

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produced by this energy, and a mass spectrometer records the masses of these ions. This

technique is so sensitive that microgram quantities of analyte can be detected by the instrument.

One of the main uses of this instrument is to determine the molecular weights and formulas of

various compounds6.

Unfortunately, not only has the performance-enhancing drug epidemic hit the

professional athletes, but it also has infected many teen athletes. Teens are driven to take these

drugs by competitive pressure, body image issues, desire to emulate star athletes, and an easy

access to athletic success without work. In a 2004 study, the National Institute on Drug Abuse

found that 3.4 percent of high school seniors admitted to taking steroids. Other studies have

estimated that 1 million teenagers use the drugs. These users risk stunting their long-term growth

and other physical problems, while the depressive side effects of steroid use have been linked to

a number of teen suicides in recent years.

Reference:

1. Berg, Jeremy M., Lubert Stryer, and John L. Tymoczko. Biochemistry.

Boston: W. H. Freeman & Company, 2006. 417.

2. Berg, Jeremy M., Lubert Stryer, and John L. Tymoczko. Biochemistry.

Boston: W. H. Freeman & Company, 2006. 754.

3. Campbell, Neil A., Jane B. Reece, and Lisa A. Urry. Biology. Boston:

Benjamin-Cummings Company, 2004. 947.

4. Campbell, Neil A., Jane B. Reece, and Lisa A. Urry. Biology. Boston:

Benjamin-Cummings Company, 2004. 1015.

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5. Mohrig, Jerry R., Christina N. Hammond, and Paul F. Schatz. Techniques in

Organic Chemsitry. Boston: W. H. Freeman & Company, 2006. 190-91.

6. Mohrig, Jerry R., Christina N. Hammond, and Paul F. Schatz. Techniques in

Organic Chemsitry. Boston: W. H. Freeman & Company, 2006. 341-342.

7. Smith, Janice G. Organic Chemistry. New York: McGraw-Hill Companies,

The, 2004. 186.

8. Smith, Janice G. Organic Chemistry. New York: McGraw-Hill Companies,

The, 2004. 187.

9. Smith, Janice G. Organic Chemistry. New York: McGraw-Hill Companies,

The, 2004. 963.

10. Smith, Janice G. Organic Chemistry. New York: McGraw-Hill Companies,

The, 2004. 960-964.

11. Zumdahl, Steven S., and Susan A. Zumdahl. Chemistry. Boston:

Houghton Mifflin College Division, 2002. 679.

Literature Search

I began my search for hunting down information by going on the search engine google.

Once I was on google I began typing in various components closely related to performance

enhancing drugs. Some of the words/phrases typed into google were biochemical effects of

performance enhancing drugs, testosterone, creatine, performance enhancing drugs in sports

today, and a wide array of other words/phrases were also typed into the search engine.

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 After browsing website after website I quickly began to grasp background knowledge of

my topic of research. However, this background knowledge of the biochemical effects of

performance enhancing drugs on the body was not sufficient enough so I hit the books. The

search for more knowledge began at the library. Unfortunately, I found that I was spending to

many hours at the library without getting the results I desired. Without luck at the library I

decided to try to find articles off of scifinder. This to yielded fruitless results. I later went back

to the library, and found a couple of sources.

Although I finally found a source other than websites it still was not enough. Desperate I

began browsing through all my science textbooks that I saved since freshman year. This is

where the majority of my sources came from. I found the structural features of three of the

selected performance enhancing drugs (testosterone, amphetamine, and methylphenidate) in my

organic chemistry book from sophomore year. Information on ephedra was found in both my

biochemistry book from this year, and my general chemistry book from freshman year. Gas-

liquid chromatography and mass spectroscopy were both located the organic techniques textbook

I got for organic lab last year. Steroid binding as well as other information was found in my

biology book from freshman year.

Even though I was finally finding information pertaining to the biochemical effects

performance enhancing drugs have on the human body there was still an integral piece missing.

The effects that each of these individual drugs have on the human body was not located in any of

the textbooks from my home collection, and I had trouble finding this information at the library

as well. It was at this point when I decided to find the side effects of each individual drug by

means of the internet. I typed in side effects at moderate and extreme amounts of the following

drugs: testosterone, anabolic steroids, creatine, amphetamine, methylphenidate, human growth

hormone (HGH), ephedra, and diuretics. I found all the necessary information about side effects

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this way, but I was unfortunately able to site any of this information due to it being taking from

the internet. The picture of the ephedra and biosynthesis of creatine was grabbed off the internet,

and all of the structural drawings were created in chem.draw

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