ATP Other Nucleotides and Nucleic Acids

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Nucleotides are organic compounds with three principal components—a single or double carbon-nitrogen ring called a nitrogenous base, a monosaccharide, and one or more phosphate groups. One of the best-known nucleotides is ATP (fig. 2.29a), in which the nitrogenous base is a double ring called adenine, the sugar is ribose, and there are three phosphate groups.

Adenosine Triphosphate

Adenosine triphosphate (ATP) is the body's most important energy-transfer molecule. It briefly stores energy gained from exergonic reactions such as glucose oxidation and releases it within seconds for physiological work such as polymerization reactions, muscle contraction, and pumping ions through cell membranes. The second and third phosphate groups of ATP are attached to the rest of the molecule by high-energy covalent bonds traditionally indicated by a wavy line in the molecular formula. Since phosphate groups are negatively charged, they repel each other. It requires a high-energy bond to overcome that repulsive force and hold them together—especially to add the third phosphate group to a chain that already has two negatively charged phosphates. Most energy transfers to and from ATP involve adding or removing that third phosphate.

Enzymes called adenosine triphosphatases (ATPases) are specialized to hydrolyze the third high-energy phos-

Chapter 2 The Chemistry of Life 85

phate bond, producing adenosine diphosphate (ADP) and an inorganic phosphate group (PJ. This reaction releases 7.3 kilocalories of energy for every mole (505 g) of ATP. Most of this energy escapes as heat, but we live on the portion of it that does useful work. We can summarize this as follows:

Heat

Work

The free phosphate groups released by ATP hydrolysis are often added to enzymes or other molecules to activate them. This addition of Pi, called phosphorylation, is carried out by enzymes called kinases (phosphokinases). The phosphorylation of an enzyme is sometimes the "switch" that turns a metabolic pathway on or off.

ATP is a short-lived molecule, usually consumed within 60 seconds of its formation. The entire amount in the body would support life for less than 1 minute if it were not continually replenished. At a moderate rate of physical activity, a full day's supply of ATP would weigh twice as much as you do. Even if you never got out of bed, you would need about 45 kg (99 lb) of ATP to stay alive for a day. The reason cyanide is so lethal is that it halts ATP synthesis.

ATP synthesis is explained in detail in chapter 26, but you will find it necessary to understand the general idea of it before you reach that chapter—especially in understanding muscle physiology (chapter 11). Much of the energy for ATP synthesis comes from glucose oxidation (fig. 2.30). The

Ribose

Triphosphate O O

Figure 2.29 Adenosine Triphosphate (ATP) and Cyclic Adenosine Monophosphate (cAMP). (a) ATP. The last two P~O bonds in ATP, indicated by wavy lines, are high-energy bonds. (b) cAMP.

Saladin: Anatomy & Physiology: The Unity of Form and Function, Third Edition

2. The Chemistry of Life Text

86 Part One Organization of the Body

which releases energy which is used for

ADP + Pi which is used for

which is then available for

Muscle contraction Ciliary beating Active transport Synthesis reactions etc.

Figure 2.30 The Source and Uses of ATP.

first stage in glucose oxidation (fig. 2.31) is the reaction pathway known as glycolysis (gly-COLL-ih-sis). This literally means "sugar splitting," and indeed its major effect is to split the six-carbon glucose molecule into two three-carbon molecules of pyruvic acid. A little ATP is produced in this stage (a net yield of two ATPs per glucose), but most of the chemical energy of the glucose is still in the pyruvic acid.

What happens to pyruvic acid depends on whether or not oxygen is available. If not, pyruvic acid is converted to lactic acid by a pathway called anaerobic29 (AN-err-OH-bic) fermentation. This pathway has two noteworthy disadvantages: First, it does not extract any more energy from pyruvic acid; second, the lactic acid it produces is toxic, so most cells can use anaerobic fermentation only as a temporary measure. The only advantage to this pathway is that it enables glycolysis to continue (for reasons explained in chapter 26) and thus enables a cell to continue producing a small amount of ATP.

If oxygen is available, a more efficient pathway called aerobic respiration occurs. This breaks pyruvic acid down to carbon dioxide and water and generates up to 36 more molecules of ATP for each of the original glucose molecules. The reactions of aerobic respiration are carried out in the cell's mitochondria (described in chapter 3), so mitochondria are regarded as a cell's principal "ATP factories."

an = without + aer = air + obic = pertaining to life

Glycolysis

Anaerobic fermentation

Glucose f

2 ATP

Pyruvic acid

No oxygen available

Lactic acid

Aerobic respiration

Oxygen available

2 ATP

Pyruvic acid

Oxygen available

No oxygen available

Mitochondrion

Anaerobic Fermentation Anatomy

36 ATP

Lactic acid

Figure 2.31 ATP Production. Glycolysis produces pyruvic acid and a net gain of two ATPs. In the absence of oxygen, anaerobic fermentation is necessary to keep glycolysis running and producing a small amount of ATP. In the presence of oxygen, aerobic respiration occurs in the mitochondria and produces a much greater amount of ATP.

Mitochondrion

36 ATP

Figure 2.31 ATP Production. Glycolysis produces pyruvic acid and a net gain of two ATPs. In the absence of oxygen, anaerobic fermentation is necessary to keep glycolysis running and producing a small amount of ATP. In the presence of oxygen, aerobic respiration occurs in the mitochondria and produces a much greater amount of ATP.

Other Nucleotides

Guanosine (GWAH-no-seen) triphosphate (GTP) is another nucleotide involved in energy transfers. In some reactions, it donates phosphate groups to other molecules. In some pathways, it donates its third phosphate group to ADP to regenerate ATP.

Cyclic adenosine monophosphate (cAMP) (see fig. 2.29b) is a nucleotide formed by the removal of both the second and third phosphate groups from ATP. In some cases, when a hormone or other chemical signal ("first messenger") binds to a cell surface, it triggers an internal reaction that converts ATP to cAMP. The cAMP then acts as a "second messenger" to activate metabolic effects within the cell.

Nucleic Acids

Nucleic (new-CLAY-ic) acids are polymers of nucleotides. The largest of them, deoxyribonucleic acid (DNA), is typically 100 million to 1 billion nucleotides long. It constitutes our genes, gives instructions for synthesizing all of

Saladin: Anatomy & I 2. The Chemistry of Life I Text I I © The McGraw-Hill

Physiology: The Unity of Companies, 2003 Form and Function, Third Edition the body's proteins, and transfers hereditary information from cell to cell when cells divide and from generation to generation when organisms reproduce. Three forms of ribonucleic acid (RNA), which range from 70 to 10,000 nucleotides long, carry out those instructions and synthesize the proteins, assembling amino acids in the right order to produce each protein "described" by the DNA. The detailed structure of DNA and RNA and the mechanisms of protein synthesis and heredity are described in chapter 4.

Before You Go On

Answer the following questions to test your understanding of the preceding section:

16. Which reaction—dehydration synthesis or hydrolysis—converts a polymer to its monomers? Which one converts monomers to a polymer? Explain your answer.

17. What is the chemical name of blood sugar? What carbohydrate is polymerized to form starch and glycogen?

18. What is the main chemical similarity between carbohydrates and lipids? What are the main differences between them?

19. Explain the statement, All proteins are polypeptides but not all polypeptides are proteins.

20. Which is more likely to be changed by heating a protein, its primary structure or its tertiary structure? Explain.

21. Use the lock and key analogy to explain why excessively acidic body fluids (acidosis) could destroy enzyme function.

22. How does ATP change structure in the process of releasing energy?

23. What advantage and disadvantage does anaerobic fermentation have compared to aerobic respiration?

24. How is DNA related to nucleotides?

Insight 2.5 Clinical Application

Anabolic-Androgenic Steroids

The sex hormone testosterone stimulates muscular growth and aggressive behavior, especially in males. In Nazi Germany, testosterone was given to SS troops in an effort to make them more aggressive, but with no proven success. In the 1950s, pharmaceutical companies developed compounds related to testosterone, called anabolic-androgenic30 steroids, to treat anemia, breast cancer, osteoporosis, and some mus-

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cle diseases, and to prevent the shrinkage of muscles in immobilized patients. By the early 1960s, athletes were using anabolic-androgenic steroids to stimulate muscle growth, accelerate the repair of tissues damaged in training or competition, and stimulate the aggressiveness needed to excel in some contact sports such as football and boxing.

The doses used by athletes, however, are 10 to 1,000 times higher than the doses prescribed for medical purposes, and they can have devastating effects on one's health. They raise cholesterol levels, which promotes fatty degeneration of the arteries (atherosclerosis). This can lead to coronary artery disease, heart and kidney failure, and stroke. Deteriorating blood circulation also sometimes results in gangrene, which may require amputation of the extremities. As the liver attempts to dispose of the high concentration of steroids, liver cancer and other liver diseases may ensue. In addition, steroids suppress the immune system, so the user is more subject to infection and cancer. They cause a premature end to bone elongation, so people who use anabolic steroids in adolescence may never attain normal adult height.

Anabolic-androgenic steroids have the same effect on the brain as natural testosterone. Thus, when steroid levels are high, the brain and pituitary gland stop producing the hormones that stimulate sperm production and testosterone secretion. In men, this leads to atrophy of the testes, impotence (inability to achieve or maintain an erection), low sperm count, and infertility. Ironically, anabolic-androgenic steroids have feminizing effects on men and masculinizing effects on women. Men may develop enlarged breasts (gynecomastia), while in some female users the breasts and uterus atrophy, the clitoris enlarges, and ovulation and menstruation become irregular. Female users may develop excessive facial and body hair and a deeper voice, and both sexes show an increased tendency toward baldness.

Especially in men, steroid abuse can be linked to severe emotional disorders. The steroids themselves stimulate heightened aggressiveness and unpredictable mood swings, so the abuser may vacillate between depression and violence. It surely doesn't help matters that impotence, shrinkage of the testes, infertility, and enlargement of the breasts are so incongruous with the self-image of a male athlete who abuses steroids.

Partly because of the well documented adverse health effects, the use of anabolic-androgenic steroids has been condemned by the American Medical Association and American College of Sports Medicine and banned by the International Olympic Committee, National Football League, and National Collegiate Athletic Association. But in spite of such warnings and bans, many athletes continue to use steroids and related performance-enhancing drugs, which remain available through unscrupulous coaches, physicians, Internet sources, and foreign mailorder suppliers. By some estimates, as many as 80% of weight lifters, 30% of college and professional athletes, and 20% of male high-school athletes now use anabolic-androgenic steroids. The National Institutes of Health finds increasing usage among high school students in recent years, and increasing denial that anabolic-androgenic steroids present a significant health hazard.

30andro = male + genic = producing

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Responses

  • piera
    Why does excessive acidic body fluids ( acidosis) destroy enzyme function?
    9 years ago
  • Lily
    How does acidosis destory enzyme funciton?
    9 years ago
  • jan-erik
    Why acidosis can destroy an enzyme's function vs lock and key analogy?
    8 years ago
  • milla
    Why excessively acidic body fluids (acidosis) could destroy enzyme function.?
    8 years ago
  • hyiab
    Why excessively acidic body fluids could destroy enzyme function lock and key analogy?
    5 years ago

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