Título del gráfico
CAPITULO 4: CURSO DE FORMACIÓN/CAPACITACION DOCENTE
4.2. Modalidad de estudios
The complex pattern of enzymatic reactions that constitutes metabolism cannot be explained entirely in terms of physico-chemical laws or chance happenings. Although some enzymes appear to function automatically, the activity of others is rigidly controlled. In the former case, suppose that the function of an enzyme is to convert A to B. If B is removed by conversion into another compound, the enzyme tends to restore the origi-nal ratio of B to A. Since many enzymes act reversibly, either synthesis or degradation may result. For example, an excess of an intermediate in the Krebs cycle would contribute to glycogen
synthesis; a depletion of such a metabolite would lead to glyco-gen breakdown. This automatic compensation (equilibration) is not, however, suffi cient to explain regulation of metabolism.
Mechanisms exist for critically regulating enzymes in both quantity and activity. In bacteria, genes leading to synthesis of an enzyme are switched on or off, depending on the presence or absence of a substrate molecule. In this way the quantity of an enzyme is controlled. It is a relatively imprecise process.
Mechanisms that alter activity of enzymes can quickly and fi nely adjust metabolic pathways to changing conditions in a cell.
The presence or increase in concentration of some molecules can alter the shape (conformation) of particular enzymes, thus activat-ing or inhibitactivat-ing the enzyme ( Figure 4.19 ). For example, phos-phofructokinase, which catalyzes phosphorylation of glucose-6-phosphate to fructose-1,6-bisphosphate (see Figure 4.15 ), is inhibited by high concentrations of ATP or citric acid. Their presence means that a sufficient amount of precursors has reached the Krebs cycle and additional glucose is not needed.
In some cases, the fi nal end product of a particular metabolic pathway inhibits the fi rst enzyme in the pathway. This method is termed feedback inhibition.
As well as being subject to alteration in physical shape, many enzymes exist in both an active and an inactive form.
These forms may be chemically different. For example, one com-mon way to activate or inactivate an enzyme is to add a phos-phate group to the molecule, thus changing its conformational shape and either exposing or blocking the enzyme’s active site.
Enzymes that degrade glycogen (phosphorylase) and synthesize it (synthase) are both found in active and inactive forms. Condi-tions that activate phosphorylase tend to inactivate synthase and vice versa.
Figure 4.19
Enzyme regulation. A, The active site of an enzyme may only loosely fi t its substrate in the absence of an activator. B, With the regulatory site of the enzyme occupied by an activator, the enzyme binds the substrate, and the site becomes catalytically active.
Substrate
Activator
A B
Regulatory site
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w w w . m h h e . c o m / h i c k m a n i p z 1 4 e CHAPTER 4 Cellular Metabolism 73
Living systems are subject to the same laws of thermodynamics that govern nonliving systems. The fi rst law states that energy cannot be destroyed, although it may change form. The second law states that the structure of systems proceeds toward total randomness, or increasing entropy, as energy is dissipated. Solar energy trapped by photosynthesis as chemical bond energy is passed through the food chain where it is used for biosynthesis, active transport, and motion, before fi nally being dissipated as heat. Living organisms are able to decrease their entropy and to maintain high internal order because the biosphere is an open system from which energy can be cap-tured and used. Energy available for use in biochemical reactions is termed “free energy.”
Enzymes are usually proteins, often associated with nonprotein cofactors, that vastly accelerate rates of chemical reactions in living systems. An enzyme acts by temporarily binding its reactant (sub-strate) onto an active site in a highly specifi c fi t. In this confi guration, internal activation energy barriers are lowered enough to modify the substrate, and the enzyme is restored to its original form.
Cells use the energy stored in chemical bonds of organic fuels by degrading fuels through a series of enzymatically controlled steps. This bond energy is transferred to ATP and packaged in the form of “high-energy” phosphate bonds. ATP is produced as it is required in cells to power various synthetic, secretory, and mechani-cal processes.
Glucose is an important source of energy for cells. In aero-bic metabolism (respiration), the 6-carbon glucose is split into two 3-carbon molecules of pyruvic acid. Pyruvic acid is decarboxylated to form 2-carbon acetyl-CoA, a strategic intermediate that enters the Krebs cycle. Acetyl-CoA can also be derived from breakdown of fat.
In the Krebs cycle, acetyl-CoA is oxidized in a series of reactions to carbon dioxide, yielding, in the course of the reactions, energized electrons that are passed to electron acceptor molecules (NAD ⫹ and FAD). In the fi nal stage, the energized electrons are passed along
an electron transport chain consisting of a series of electron carriers located in the inner membranes of mitochondria. A hydrogen gradi-ent is produced as electrons are passed from carrier to carrier and fi nally to oxygen, and ATP is generated as the hydrogen ions fl ow down their electrochemical gradient through ATP synthase mole-cules located in the inner mitochondrial membrane. A net total of 36 molecules of ATP may be generated from one molecule of glucose.
In the absence of oxygen (anaerobic glycolysis), glucose is degraded to two 3-carbon molecules of lactic acid, yielding two mol-ecules of ATP. Although anaerobic glycolysis is vastly less effi cient than aerobic metabolism, it provides essential energy for muscle contraction when heavy energy expenditure outstrips the oxygen-delivery system of an animal; it also is the only source of energy generation for microorganisms living in oxygen-free environments.
Triglycerides (neutral fats) are especially rich depots of meta-bolic energy because the fatty acids of which they are composed are highly reduced and free of water. Fatty acids are degraded by sequential removal of 2-carbon units, which enter the Krebs cycle through acetyl-CoA.
Amino acids in excess of requirements for synthesis of proteins and other biomolecules are used as fuel. They are degraded by deam-ination or transamdeam-ination to yield ammonia and carbon skeletons.
The latter enter the Krebs cycle to be oxidized. Ammonia is a highly toxic waste product that aquatic animals quickly expel, often through respiratory surfaces. Terrestrial animals, however, convert ammonia into much less toxic compounds, urea or uric acid, for disposal.
Integration of metabolic pathways is fi nely regulated by mecha-nisms that control both amount and activity of enzymes. The quan-tity of some enzymes is regulated by certain molecules that switch on or off enzyme synthesis. Enzyme activity may be altered by the presence or absence of metabolites that cause conformational changes in enzymes and thus improve or diminish their effective-ness as catalysts.
S U M M A R Y
R E V I E W Q U E S T I O N S
State the fi rst and second laws of thermodynamics.
Living systems may appear to violate the second law of thermodynamics because living things maintain a high degree of organization despite a universal trend toward increasing disorganization. What is the explanation for this apparent paradox?
Explain what is meant by “free energy” in a system. Will a reaction that proceeds spontaneously have a positive or negative change in free energy?
Many biochemical reactions proceed slowly unless the energy barrier to the reaction is lowered. How is this accomplished in living systems?
What happens in the formation of an enzyme-substrate complex that favors the disruption of substrate bonds?
What is meant by a “high-energy bond,” and why might the production of molecules with such bonds be useful to living organisms?
Although ATP supplies energy to an endergonic reaction, why is it not considered a fuel?
1.
2.
3.
4.
5.
6.
What is an oxidation-reduction reaction and why are such reactions considered so important in cellular metabolism?
Give an example of a fi nal electron acceptor found in aerobic and anaerobic organisms. Why is aerobic metabolism more effi cient than anaerobic metabolism?
Why must glucose be “primed” with a high-energy phosphate bond before it can be degraded in the glycolytic pathway?
What happens to the electrons removed during the oxidation of triose phosphates during glycolysis?
Why is acetyl-CoA considered a “strategic intermediate” in respiration?
Why are oxygen atoms important in oxidative
phosphorylation? What are the consequences if they are absent for a short period of time in tissues that routinely use oxidative phosphorylation to produce useful energy?
Explain how animals can generate ATP without oxygen. Given that anaerobic glycolysis is much less effi cient than oxidative phosphorylation, why has anaerobic glycolysis not been discarded during animal evolution?
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Why are animal fats sometimes called “the king of fuels”? What is the signifi cance of acetyl-CoA to lipid metabolism?
The breakdown of amino acids yields two products: ammonia and carbon skeletons. What happens to these products?
14.
15.
Explain the relationship between the amount of water in an animal’s environment and the kind of nitrogenous waste it produces.
Explain three ways that enzymes may be regulated in cells.
16.
17.
S E L E C T E D R E F E R E N C E S
Alberts, B., D. Bray, K. Hopkin, A. Johnson, J. Lewis, M. Raff, K. Roberts, and P. Walter. 2003. Essential cell biology, ed. 2. New York, Garland Science Publishing. Provides a more in-depth and well-written description of cellular metabolism.
Berg, J., J. Tymoczko, and L. Stryer. 2002. Biochemistry, ed. 5. San Francisco, W. H. Freeman & Company. One of the best undergraduate biochemistry texts.
Lodish, H., A. Berk, S. L. Zipursky, P. Matsudaira, D. Baltimore, and J. Darnell. 2000. Molecular cell biology, ed. 4. San Francisco, W. H.
Freeman & Company. Chapter 16 is a comprehensive, well-illustrated treatment of energy metabolism.
Wolfe, S. L. 1995. Introduction to cell and molecular biology. Belmont, CA.
Thomson Brooks/Cole Publishers. Covers the same topics as Wolfe’s big book, but in less detail.
O N L I N E L E A R N I N G C E N T E R
Visit www.mhhe.com/hickmanipz14e for chapter quizzing, key term fl ash cards, web links, and more!
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P A R T T W O
2
Genetics: A Review Organic Evolution The Reproductive Process Principles of Development 5
6 7 8
Continuity and Evolution of Animal Life
A female Cardinalis cardinalis (left) and a female Cardinalis sinuatus (right).
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of the coded instructions in genes. The genetic material (deoxyribo-nucleic acid, DNA) is composed of nitrogenous bases arranged on a chemical chain of sugar-phosphate units. The genetic code lies in the linear order or sequence of bases in the DNA strand.
Because the DNA molecules replicate and pass from generation to generation, genetic variations can persist and spread in a popula-tion. Such molecular alterations, called mutations, are the ultimate source of biological variation and the raw material of evolution.
5
Genetics: A Review
A Code for All Life
The principle of hereditary transmission is a central tenet of life on earth: all organisms inherit a structural and functional organization from their progenitors. What is inherited by an offspring is not an exact copy of the parent but a set of coded instructions that a devel-oping organism uses to construct a body resembling its parents.
These instructions are in the form of genes, the fundamental units of inheritance. One of the great triumphs of modern biology was the discovery in 1953 by James Watson and Francis Crick of the nature
The site of Gregor Mendel’s experimental garden, Brno, Czech Republic.
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w w w . m h h e . c o m / h i c k m a n i p z 1 4 e CHAPTER 5 Genetics: A Review 77
A
basic principle of modern evolutionary theory is that organ-isms attain their diversity through hereditary modifi cations of populations. All known lineages of plants and animals are related by descent from common ancestral populations.Heredity establishes the continuity of living forms. Although off-spring and parents in a particular generation may look different, there is nonetheless a genetic continuity that runs from generation to genera-tion for any species of plant or animal. An offspring inherits from its parents a set of coded information (genes), which a fertilized egg uses, together with environmental factors, to guide its development into an adult bearing unique physical characteristics. Each generation passes to the next the instructions required for maintaining continuity of life.
The gene is the unit entity of inheritance, the germinal basis for every characteristic that appears in an organism. The study of what genes are, how they are transmitted, and how they work is the sci-ence of genetics. It is a scisci-ence that reveals the underlying causes of resemblance, as seen in the remarkable fi delity of reproduction, and of variation, the working material for organic evolution. All liv-ing forms use the same information storage, transfer, and translation system, which explains the stability of all life and reveals its descent from a common ancestral form. This is one of the most important unifying concepts of biology.