《生物化学》课程教学资源（书籍文献）经典教材 Lehninger Principles of Biochemistry, SIXTH EDITION, David L. Nelson, Michael M. Cox

2 The Foundations of Biochemistru FIGURE 1-2 Diverse living fo tures.Birds b asts plants a am DN acid).They the sam (e) romThe Gardenof Eden,byJan van Kessel the Younger (1621679) FIGURE 1-1 Som harasteristics of living matter.(a)Mi compkahyandorganzatomareapparentinthscolortedimgeoah smingasnmalerbdteBologcalreprodtcionocaurswihnearpeicc e range of spec chemical fr .Fo ach elity clarity,in this book we sometimes risk certain general a billion identical"daughte n24 hours.Each ations,which,though not perfect,remai se gene some extremely complex;yet each bacterium is a alizations.which can prove illuminating Biochemistry describes in molecular terms the stru tures,mechan e of the chemicalproce h progeny of a vertebrate animal share a striking lectively as the molecular logic of life.Although bio A capacity to change over time by gradual evolu try,its ultimate concem is with the wonder of life itself nge th ve give an o The of tenoibcemicph arching principle diversity of life fomms,superficiallyv of evolution-how life emerged and evolved into the (Fig.1-2)bu organisms we toda As you rea organisms is refected at the molecular level in the to this chanter at inte similarity of gene sequences and protein structures this background material. Despite the nd the funds 1.1 Cellular Foundations and are multicellula

2 The Foundations of Biochemistry to college dormitories, is matched by a correspondingly wide range of specific biochemical adaptations, achieved within a common chemical framework. For the sake of clarity, in this book we sometimes risk certain general￾izations, which, though not perfect, remain useful; we also frequently point out the exceptions to these gener￾alizations, which can prove illuminating. Biochemistry describes in molecular terms the struc￾tures, mechanisms, and chemical processes shared by all organisms and provides organizing principles that under￾lie life in all its diverse forms, principles we refer to col￾lectively as the molecular logic of life. Although bio￾chemistry provides important insights and practical applications in medicine, agriculture, nutrition, and indus￾try, its ultimate concern is with the wonder of life itself. In this introductory chapter we give an overview of the cellular, chemical, physical, and genetic back￾grounds to biochemistry and the overarching principle of evolution—how life emerged and evolved into the diversity of organisms we see today. As you read through the book, you may find it helpful to refer back to this chapter at intervals to refresh your memory of this background material. 1.1 Cellular Foundations The unity and diversity of organisms become apparent even at the cellular level. The smallest organisms consist of single cells and are microscopic. Larger, multicellular a billion identical “daughter” cells in 24 hours. Each cell contains thousands of different molecules, some extremely complex; yet each bacterium is a faithful copy of the original, its construction directed entirely from information contained in the genetic material of the original cell. On a larger scale, the progeny of a vertebrate animal share a striking resemblance to their parents, also the result of their inheritance of parental genes. A capacity to change over time by gradual evolu￾tion. Organisms change their inherited life strategies, in very small steps, to survive in new circumstances. The result of eons of evolution is an enormous diversity of life forms, superficially very different (Fig. 1–2) but fundamentally related through their shared ancestry. This fundamental unity of living organisms is reflected at the molecular level in the similarity of gene sequences and protein structures. Despite these common properties, and the funda￾mental unity of life they reveal, it is difficult to make generalizations about living organisms. Earth has an enormous diversity of organisms. The range of habitats, from hot springs to Arctic tundra, from animal intestines FIGURE 1–2 Diverse living organisms share common chemical fea￾tures. Birds, beasts, plants, and soil microorganisms share with humans the same basic structural units (cells) and the same kinds of macromol￾ecules (DNA, RNA, proteins) made up of the same kinds of monomeric subunits (nucleotides, amino acids). They utilize the same pathways for synthesis of cellular components, share the same genetic code, and derive from the same evolutionary ancestors. Shown here is a detail from “TheGarden of Eden,” by Jan van Kessel the Younger(1626“1679). FIGURE 1–1 Some characteristics of living matter. (a) Microscopic complexity and organization are apparent in this colorized image of a thin section of a secretory cell from the pancreas, viewed with the electron microscope. (b) A prairie falcon acquires nutrients and energy by con￾suming a smaller bird. (c) Biological reproduction occurs with near-perfect fidelity. (b) (c) (a)

1.1 Cellular Foundations organisms contain many different types of cells,which concentrated solution containing enzymes and the RNA most complex organisms share certain fundamental 'aeadndeoin2ftoegmoanemoeolea7 are as properties,which can be seen at the biochemical level. Cells Are the Structural and Functional Units of All Living Organisms All cells have,for at least some part of their life,either a nucleus,in v Cells of all kinds share certain structural features a nucleo (Fig. The plasma m brane dennes the perpn and stored.with proteins.The nucleod.in bacteria and archaea,is not separated from the cytoplasm tough,pliable,hydrophobic barrier with nuclear envelopes make up the large domain Eukarya (Greek "nucl (G recognized as comprising two very distinct groups:the domains Bacteria and Archaea,described below athare not ntynko membrane not covale Cellular Dimensions Are Limited by Diffusion ded eye made lipid and protein molecules are inserted into its 2 um long (see the inside back cover for information on (fission)occurs without loss of membrane integrity. t by the plasma mem- minimum number of each type of biomolecule required by the cell.The smallest cells, certain bacteria kno vn as particles with specific functions s.These particulate com eria ave a 20nm in its longest dimension,soa few ribosomes takeu a substantial of the and degradation)sediment when cytoplasm is centrifuge ules at150,000 e cyt consuming reac medium through its plasma membrane.The cel is small,and the ratio of its surface area to its volume is s Cytoplas asm is eas -Plasm ell size 50 however,surface-to-volume ratio decreases unti than ciffusion can su sible as cell siz ing a theoretical upper limit on the size of cells.Oxyge Bacterial cell Animal cell is only or e of many low me FIGRE1-3 The universal features of living cells.All cells have its interior.and the sme surface-to-volume arument applies to each of them as well. i dofinnd a tha in th sup and centrif There Are Three Distinct Domains of Life All living organisms fall into one of three large groups asts)and large particles (),which by this ce nd can be rec ene origin progen

1.1 Cellular Foundations 3 concentrated solution containing enzymes and the RNA molecules that encode them; the components (amino acids and nucleotides) from which these macromolecules are assembled; hundreds of small organic molecules called metabolites, intermediates in biosynthetic and degrada￾tive pathways; coenzymes, compounds essential to many enzyme-catalyzed reactions; and inorganic ions. All cells have, for at least some part of their life, either a nucleoid or a nucleus, in which the genome—the complete set of genes, composed of DNA—is replicated and stored, with its associated proteins. The nucleoid, in bacteria and archaea, is not separated from the cytoplasm by a membrane; the nucleus, in eukaryotes, is enclosed within a double membrane, the nuclear envelope. Cells with nuclear envelopes make up the large domain Eukarya (Greek eu, “true,” and karyon, “nucleus”). Microorgan￾isms without nuclear membranes, formerly grouped together as prokaryotes (Greek pro, “before”), are now recognized as comprising two very distinct groups: the domains Bacteria and Archaea, described below. Cellular Dimensions Are Limited by Diffusion Most cells are microscopic, invisible to the unaided eye. Animal and plant cells are typically 5 to 100 mm in diam￾eter, and many unicellular microorganisms are only 1 to 2 mm long (see the inside back cover for information on units and their abbreviations). What limits the dimen￾sions of a cell? The lower limit is probably set by the minimum number of each type of biomolecule required by the cell. The smallest cells, certain bacteria known as mycoplasmas, are 300 nm in diameter and have a volume of about 10214 mL. A single bacterial ribosome is about 20 nm in its longest dimension, so a few ribosomes take up a substantial fraction of the volume in a mycoplasmal cell. The upper limit of cell size is probably set by the rate of diffusion of solute molecules in aqueous systems. For example, a bacterial cell that depends on oxygen￾consuming reactions for energy extraction must obtain molecular oxygen by diffusion from the surrounding medium through its plasma membrane. The cell is so small, and the ratio of its surface area to its volume is so large, that every part of its cytoplasm is easily reached by O2 diffusing into the cell. With increasing cell size, however, surface-to-volume ratio decreases, until metabolism consumes O2 faster than diffusion can sup￾ply it. Metabolism that requires O2 thus becomes impos￾sible as cell size increases beyond a certain point, plac￾ing a theoretical upper limit on the size of cells. Oxygen is only one of many low molecular weight species that must diffuse from outside the cell to various regions of its interior, and the same surface-to-volume argument applies to each of them as well. There Are Three Distinct Domains of Life All living organisms fall into one of three large groups (domains) that define three branches of the evolution￾ary tree of life originating from a common progenitor organisms contain many different types of cells, which vary in size, shape, and specialized function. Despite these obvious differences, all cells of the simplest and most complex organisms share certain fundamental properties, which can be seen at the biochemical level. Cells Are the Structural and Functional Units of All Living Organisms Cells of all kinds share certain structural features (Fig. 1–3). The plasma membrane defines the periph￾ery of the cell, separating its contents from the sur￾roundings. It is composed of lipid and protein molecules that form a thin, tough, pliable, hydrophobic barrier around the cell. The membrane is a barrier to the free passage of inorganic ions and most other charged or polar compounds. Transport proteins in the plasma membrane allow the passage of certain ions and mole￾cules; receptor proteins transmit signals into the cell; and membrane enzymes participate in some reaction pathways. Because the individual lipids and proteins of the plasma membrane are not covalently linked, the entire structure is remarkably flexible, allowing changes in the shape and size of the cell. As a cell grows, newly made lipid and protein molecules are inserted into its plasma membrane; cell division produces two cells, each with its own membrane. This growth and cell division (fission) occurs without loss of membrane integrity. The internal volume enclosed by the plasma mem￾brane, the cytoplasm (Fig. 1–3), is composed of an aqueous solution, the cytosol, and a variety of suspended particles with specific functions. These particulate com￾ponents (membranous organelles such as mitochondria and chloroplasts; supramolecular structures such as ribo￾somes and proteasomes, the sites of protein synthesis and degradation) sediment when cytoplasm is centrifuged at 150,000 g (g is the gravitational force of Earth). What remains as the supernatant fluid is the cytosol, a highly FIGURE 1–3 The universal features of living cells. All cells have a nucleus or nucleoid containing their DNA, a plasma membrane, and cytoplasm. The cytosol is defined as that portion of the cytoplasm that remains in the supernatant after gentle breakage of the plasma membrane and centrifu￾gation of the resulting extract at 150,000 g for 1 hour. Eukaryotic cells contain a variety of membrane-bounded organelles (mitochondria, chloro￾plasts) and large particles (ribosomes, for example), which are sedimented by this centrifugation and can be recovered from the pellet. Nelson/Cox Lehninger Biochemistry, 6e ISBN13: 1-4292-3414-8 Figure #1.03 Permanent figure # 104 1st pass 1 mm Bacterial cell Animal cell Cytoplasm Plasma membrane Ribosomes Nucleus Nucleoid Nuclear membrane Membrane-bounded organelles 50 mm

The Foundations of Biochemistru Eukarya Bacteria Archae Halophil Microsporidia nonads Last universal on ancestor FIGURE 1-4 Phyl of life.Phylogenetic rela dfrom similaritie ecies of the acid sequences of the oELaheciernalprotanh the rence between two sequences.Phylogenetic trees can (e) ad cate grounds:Bacteria and Archaea Bacteria inhabit soils (Greektrop"nourishment")trap and use sunlight,and chemotrophs denv domain b Car Woese in the 19s0s.inhabit extreme HS-to S(elemental sulfur),Sto 4 for example.Phototrophs and chemotrophs furt r t can synthe tion.All eukaryotic organisms.which make up the thir those that require some preformed organic nutrients made omain,Eukarya.vo cukarvotes are therefore more by other organisms (heterotrophs).We can describe an s are on by ese term are chemoheterotrophs.Even ier distinctions can be by their habitats.In aerobi hade,and many organisms can obta n energy and carbor dent organisms derive from the transfer of eleo trons from fuel molecules to oxygen within the cell Bacterial and Archaeal Cells Share Common Features ments obtain energy by transferring electrons to nitrate but Differ in Important Ways (forming N),sulfate (forming H),or CO(forming The best-studied bacterium,Escherichia coli,is a usu CH).M inal trac on and a little less than m in diameter.but othe bacteria may be spherical or rod-shaped.It has a pro membr c a an inn Organisms Differ Widely in Their Sources of Energy Between the inner and outer membranes is a thin but and Biosynthetic Precursors nla e and the lay

4 The Foundations of Biochemistry material (as summarized in Fig. 1–5). There are two broad categories based on energy sources: phototrophs (Greek trophe¯, “nourishment”) trap and use sunlight, and chemotrophs derive their energy from oxidation of a chemical fuel. Some chemotrophs oxidize inorganic fuels— HS2 to S0 (elemental sulfur), S0 to to or to for example. Phototrophs and chemotrophs may be further divided into those that can synthesize all of their biomolecules directly from CO2 (autotrophs) and those that require some preformed organic nutrients made by other organisms (heterotrophs). We can describe an organism’s mode of nutrition by combining these terms. For example, cyanobacteria are photoautotrophs; humans are chemoheterotrophs. Even finer distinctions can be made, and many organisms can obtain energy and carbon from more than one source under different environmental or developmental conditions. Bacterial and Archaeal Cells Share Common Features but Differ in Important Ways The best-studied bacterium, Escherichia coli, is a usu￾ally harmless inhabitant of the human intestinal tract. The E. coli cell (Fig. 1–6a) is an ovoid about 2 mm long and a little less than 1 mm in diameter, but other bacteria may be spherical or rod-shaped. It has a pro￾tective outer membrane and an inner plasma mem￾brane that encloses the cytoplasm and the nucleoid. Between the inner and outer membranes is a thin but strong layer of a high molecular weight polymer (pepti￾doglycan) that gives the cell its shape and rigidity. The plasma membrane and the layers outside it constitute (Fig. 1–4). Two large groups of single-celled microor￾ganisms can be distinguished on genetic and biochemical grounds: Bacteria and Archaea. Bacteria inhabit soils, surface waters, and the tissues of other living or decaying organisms. Many of the Archaea, recognized as a distinct domain by Carl Woese in the 1980s, inhabit extreme environments—salt lakes, hot springs, highly acidic bogs, and the ocean depths. The available evidence suggests that the Archaea and Bacteria diverged early in evolu￾tion. All eukaryotic organisms, which make up the third domain, Eukarya, evolved from the same branch that gave rise to the Archaea; eukaryotes are therefore more closely related to archaea than to bacteria. Within the domains of Archaea and Bacteria are subgroups distinguished by their habitats. In aerobic habitats with a plentiful supply of oxygen, some resi￾dent organisms derive energy from the transfer of elec￾trons from fuel molecules to oxygen within the cell. Other environments are anaerobic, virtually devoid of oxygen, and microorganisms adapted to these environ￾ments obtain energy by transferring electrons to nitrate (forming N2), sulfate (forming H2S), or CO2 (forming CH4). Many organisms that have evolved in anaerobic environments are obligate anaerobes: they die when exposed to oxygen. Others are facultative anaerobes, able to live with or without oxygen. Organisms Differ Widely in Their Sources of Energy and Biosynthetic Precursors We can classify organisms according to how they obtain the energy and carbon they need for synthesizing cellular FIGURE 1–4 Phylogeny of the three domains of life. Phylogenetic rela￾tionships are often illustrated by a “family tree” of this type. The basis for this tree is the similarity in nucleotide sequences of the ribosomal RNAs of each group; the more similar the sequence, the closer the loca￾tion of the branches, with the distance between branches representing the degree of difference between two sequences. Phylogenetic trees can also be constructed from similarities across species of the amino acid sequences of a single protein. For example, sequences of the protein GroEL (a bacterial protein that assists in protein folding) were compared to generate the tree in Figure 3“35. The tree in Figure 3“36 is a “consensus” tree, which uses several comparisons such as these to derive the best estimates of evolutionary relatedness among a group of organisms. Proteobacteria (Purple bacteria) Cyanobacteria Flavobacteria Thermotogales Pyrodictium Thermoproteus Thermococcus Methanococcus Methanosarcina Halophiles Microsporidia Flagellates Trichomonads Plants Ciliates Fungi Diplomonads Animals Slime molds Entamoebae Archaea Last universal common ancestor Gram￾positive bacteria Bacteria Eukarya Green nonsulfur bacteria Methanobacterium

1.1 Cellular Foundations 5 All organisms Energy source Chemical Phototrophs Carbon source Organic compounds Organic Chemoheterotrophs Photoautotrophs Photo lelectron acce UseH,? an compo FIGURE 1-5 All poundsand their source by proteins.Archaeal plasma membranes have a similar of each of,different enzymes,perhaps 1,000 中心 organic compounds of molecular weight less than 1,000 specializat ons of their ce am's st layer of peptidoglycan outside their plasma membrane tance to toxins and antibiotics in the environment.In but lack an outer membrane.Gram-negative bacteria aton and and proteins called porins that provide transmembrane a similar collection of biomolecules,but each species has organism to organism,but they,too,have a layer of

1.1 Cellular Foundations 5 The cytoplasm of E. coli contains about 15,000 ribosomes, various numbers (10 to thousands) of copies of each of 1,000 or so different enzymes, perhaps 1,000 organic compounds of molecular weight less than 1,000 (metabolites and cofactors), and a variety of inorganic ions. The nucleoid contains a single, circular molecule of DNA, and the cytoplasm (like that of most bacteria) contains one or more smaller, circular segments of DNA called plasmids. In nature, some plasmids confer resis￾tance to toxins and antibiotics in the environment. In the laboratory, these DNA segments are especially ame￾nable to experimental manipulation and are powerful tools for genetic engineering (see Chapter 9). Other species of bacteria, as well as archaea, contain a similar collection of biomolecules, but each species has physical and metabolic specializations related to its envi￾ronmental niche and nutritional sources. Cyanobacteria, for example, have internal membranes specialized to trap energy from light (see Fig. 19–67). Many archaea live in extreme environments and have biochemical the cell envelope. The plasma membranes of bacteria consist of a thin bilayer of lipid molecules penetrated by proteins. Archaeal plasma membranes have a similar architecture, but the lipids can be strikingly different from those of bacteria (see Fig. 10–12). Bacteria and archaea have group-specific specializations of their cell envelopes (Fig. 1–6b–d). Some bacteria, called gram￾positive because they are colored by Gram’s stain (introduced by Hans Peter Gram in 1882), have a thick layer of peptidoglycan outside their plasma membrane but lack an outer membrane. Gram-negative bacteria have an outer membrane composed of a lipid bilayer into which are inserted complex lipopolysaccharides and proteins called porins that provide transmembrane channels for low molecular weight compounds and ions to diffuse across this outer membrane. The structures outside the plasma membrane of archaea differ from organism to organism, but they, too, have a layer of peptidoglycan or protein that confers rigidity on their cell envelopes. FIGURE 1–5  All organisms can be classified according to their source of energy (sunlight or oxidizable chemical compounds) and their source of carbon for the synthesis of cellular material. Nelson/Cox Principles of Biochemistry, 6e ISBN13: 1-4292-3414-8 Figure 01.05 Permanent figure # 106 ISBN13: 1-4292-3414-8 02-26-2012 03-13-2012 CO2 Organic compounds CO2 Organic compounds All organisms Chemical Light Energy source Chemotrophs Phototrophs Chemoheterotrophs Final electron acceptor All animals; most fungi, protists, bacteria Fermentative bacteria such as Lactococcus lactis and… …Pseudomonas denitrificans, for example Use H2O to reduce CO2? Chemoautotrophs Hydrogen-, sulfur-, iron-, nitrogen-, and carbon monoxide￾oxidizing bacteria Green nonsulfur bacteria, purple nonsulfur bacteria Oxygenic photosynthesis (plants, algae, cyanobacteria) Anoxygenic photosynthetic bacteria (green and purple bacteria) Photoautotrophs Photoheterotrophs Carbon source Carbon source O2 Yes No Not O2 Organic compounds Inorganic compounds

The Foundations of Biochemistru sfneeanrhn (b)Gram-positive bacteria olid lave Cytopla e)Gram-negati LPS Periplasm ipoprotein (d)Meth extremely heat-tolerant archae peptaetuto lasma mem Cytoplasm FIGURE 1-6 s tural fea s of ba brane (b)The ce e of gra ranemdeotphophoiphndpote s.is impermeant to both large es.Between the inner and outer gidity,but retain Gram'sstain(d)Archaeal membranes vary in on the outer surface and phospholipids on the inner surface.This oute protein shell (solid laver).or both. structure gave the first hints that Bacteria and Archaea otes are the nucleus and a variety of membrane-enclosed The e organelles to each other and to some solid substrate beneath or at ulum and Golgi complexes,which play central roles in some bact the synthesis and proces mes.filled with digestiv between neighboring cells enzymes to degrade unneeded cellular debris.In addi on to Eukaryotic Cells Have a Variety of Membranous plasts (in which sunlight drives the synthesis of ATP in Organelles,Which Can Be Isolated for Study 171 s）Fig.1 oen高aras】

6 The Foundations of Biochemistry adaptations to survive in extremes of temperature, pres￾sure, or salt concentration. Differences in ribosomal structure gave the first hints that Bacteria and Archaea constituted separate domains. Most bacteria (including E. coli) exist as individual cells, but often associate in biofilms or mats, in which large numbers of cells adhere to each other and to some solid substrate beneath or at an aqueous surface. Cells of some bacterial species (the myxobacteria, for example) show simple social behavior, forming many-celled aggregates in response to signals between neighboring cells. Eukaryotic Cells Have a Variety of Membranous Organelles, Which Can Be Isolated for Study Typical eukaryotic cells (Fig. 1–7) are much larger than bacteria—commonly 5 to 100 mm in diameter, with cell volumes a thousand to a million times larger than those of bacteria. The distinguishing characteristics of eukary￾otes are the nucleus and a variety of membrane-enclosed organelles with specific functions. These organelles include mitochondria, the site of most of the energy￾extracting reactions of the cell; the endoplasmic retic￾ulum and Golgi complexes, which play central roles in the synthesis and processing of lipids and membrane proteins; peroxisomes, in which very long-chain fatty acids are oxidized; and lysosomes, filled with digestive enzymes to degrade unneeded cellular debris. In addi￾tion to these, plant cells also contain vacuoles (which store large quantities of organic acids) and chloro￾plasts (in which sunlight drives the synthesis of ATP in the process of photosynthesis) (Fig. 1–7). Also present in the cytoplasm of many cells are granules or droplets containing stored nutrients such as starch and fat. FIGURE 1–6 Some common structural features of bacterial and archaeal cells. (a) This correct-scale drawing of E. coli serves to illustrate some common features. (b) The cell envelope of gram-positive bacteria is a single membrane with a thick, rigid layer of peptidoglycan on its outside surface. A variety of polysaccharides and other complex polymers are interwoven with the peptidoglycan, and surrounding the whole is a porous “solid layer” composed of glycoproteins. (c) E. coli is gram-negative and has a double membrane. Its outer membrane has a lipopolysaccharide (LPS) on the outer surface and phospholipids on the inner surface. This outer membrane is studded with protein channels (porins) that allow small molecules, but not proteins, to diffuse through. The inner (plasma) mem￾brane, made of phospholipids and proteins, is impermeant to both large and small molecules. Between the inner and outer membranes, in the periplasm, is a thin layer of peptidoglycan, which gives the cell shape and rigidity, but does not retain Gram's stain. (d) Archaeal membranes vary in structure and composition, but all have a single membrane surrounded by an outer layer that includes either a peptidoglycanlike structure, a porous protein shell (solid layer), or both. Nelson/Cox Lehninger Biochemistry, 6e ISBN13: 1-4292-3414-8 Figure #1.6a Permanent figure #108 2nd pass Ribosomes Bacterial and archaeal ribosomes are smaller than eukaryotic ribosomes, but serve the same function— protein synthesis from an RNA message. Nucleoid Contains one or several long, circular DNA molecules. Pili Provide points of adhesion to surface of other cells. Flagella Propel cell through its surroundings. Cell envelope structures differ. (a) (b) Gram-positive bacteria Solid layer Glycoprotein Polysaccharide Lipoprotein Peptidoglycan Plasma membrane Cytoplasm Porin Lipoprotein Lipoprotein Periplasm Peptidoglycan Plasma membrane LPS Outer membrane Cytoplasm Solid layer Glycoprotein Pseudo￾peptidoglycan Plasma membrane Cytoplasm (c) Gram-negative bacteria (shown at left) (d) Methanothermus, an extremely heat-tolerant archaeon