Contents xxvii Porphyrins are synthesized from glycine and succinyl The synthesis of purine nucleotides is controlled by coenzyme A 728 feedback inhibition at several sites 751 Porphyrins accumulate in some inherited disorders of The synthesis of deoxyribonucleotides is porphyrin metabolism 730 controlled by the regulation of ribonucleotide reductase 752 Chapter 25 Nucleotide Biosynthesis 735 25.5 Disruptions in Nucleotide Metabolism Can Cause Pathological Conditions 752 Nucleotides can be synthesized by de novo or The loss of adenosine deaminase activity results salvage pathways 736 in severe combined immunodeficiency 752 25.1 The Pyrimidine Ring Is Assembled de Gout is induced by high serum levels of urate 753 Novo or Recovered by Salvage Pathways 737 Lesch-Nyhan syndrome is a dramatic consequence Bicarbonate and other oxygenated carbon compounds of mutations in a salvage-pathway enzyme 754 are activated by phosphorylation 737 Folic acid deficiency promotes birth defects such The side chain of glutamine can be hydrolyzed to as spina bifida 755 generate ammonia 737 Intermediates can move between active sites by channeling 737 Chapter 26 The Biosynthesis of Membrane Orotate acquires a ribose ring from PRPP to Lipids and Steroids 759 form a pyrimidine nucleotide and is converted 26.1 Phosphatidate Is a Common Intermediate into uridylate 738 in the Synthesis of Phospholipids and Nucleotide mono-,di-,and triphosphates are Triacylglycerols 760 interconvertible 739 CTP is formed by amination of UTP The synthesis of phospholipids requires an activated 739 intermediate 761 Salvage pathways recycle pyrimidine bases 740 Sphingolipids are synthesized from ceramide 763 25.2 Purine Bases Can Be Synthesized de Gangliosides are carbohydrate-rich sphingolipids Novo or Recycled by Salvage Pathways 740 that contain acidic sugars 764 The purine ring system is assembled on ribose Sphingolipids confer diversity on lipid structure and phosphate 740 function 765 The purine ring is assembled by successive steps of Respiratory distress syndrome and Tay-Sachs disease activation by phosphorylation followed by result from the disruption of lipid metabolism 765 displacement 741 Phosphatiditic acid phosphatase is a key regulatory AMP and GMP are formed from IMP 743 enzyme in lipid metabolism 766 Enzymes of the purine synthesis pathway associate 26.2 Cholesterol Is Synthesized from Acetyl with one another in vivo 744 Coenzyme A in Three Stages 767 Salvage pathways economize intracellular energy The synthesis of mevalonate,which is activated as expenditure 744 isopentenyl pyrophosphate,initiates the synthesis of 25.3 Deoxyribonucleotides Are Synthesized cholesterol 767 by the Reduction of Ribonucleotides Through Squalene(C30)is synthesized from six molecules of a Radical Mechanism 745 isopentenyl pyrophosphate(Cs) 768 Mechanism:A tyrosyl radical is critical to the action Squalene cyclizes to form cholesterol 769 of ribonucleotide reductase 745 26.3 The Complex Regulation of Stable radicals other than tyrosyl radical are Cholesterol Biosynthesis Takes Place at employed by other ribonucleotide reductases 747 Several Levels 770 Thymidylate is formed by the methylation of deoxyuridylate 748 Lipoproteins transport cholesterol and triacylglycerols throughout the organism 773 Dihydrofolate reductase catalyzes the regeneration of tetrahydrofolate,a one-carbon carrier 749 The blood levels of certain lipoproteins can serve diagnostic purposes 774 Several valuable anticancer drugs block the synthesis Low-density lipoproteins play a central role in of thymidylate 749 cholesterol metabolism 775 25.4 Key Steps in Nucleotide Biosynthesis Are The absence of the LDL receptor leads to Regulated by Feedback Inhibition 750 hypercholesterolemia and atherosclerosis 776 Pyrimidine biosynthesis is regulated by aspartate Mutations in the LDL receptor prevent LDL release transcarbamoylase 751 and result in receptor destruction 777
Contents xxvii Porphyrins are synthesized from glycine and succinyl coenzyme A 728 Porphyrins accumulate in some inherited disorders of porphyrin metabolism 730 Chapter 25 Nucleotide Biosynthesis 735 Nucleotides can be synthesized by de novo or salvage pathways 736 25.1 The Pyrimidine Ring Is Assembled de Novo or Recovered by Salvage Pathways 737 Bicarbonate and other oxygenated carbon compounds are activated by phosphorylation 737 The side chain of glutamine can be hydrolyzed to generate ammonia 737 Intermediates can move between active sites by channeling 737 Orotate acquires a ribose ring from PRPP to form a pyrimidine nucleotide and is converted into uridylate 738 Nucleotide mono-, di-, and triphosphates are interconvertible 739 CTP is formed by amination of UTP 739 Salvage pathways recycle pyrimidine bases 740 25.2 Purine Bases Can Be Synthesized de Novo or Recycled by Salvage Pathways 740 The purine ring system is assembled on ribose phosphate 740 The purine ring is assembled by successive steps of activation by phosphorylation followed by displacement 741 AMP and GMP are formed from IMP 743 Enzymes of the purine synthesis pathway associate with one another in vivo 744 Salvage pathways economize intracellular energy expenditure 744 25.3 Deoxyribonucleotides Are Synthesized by the Reduction of Ribonucleotides Through a Radical Mechanism 745 Mechanism: A tyrosyl radical is critical to the action of ribonucleotide reductase 745 Stable radicals other than tyrosyl radical are employed by other ribonucleotide reductases 747 Thymidylate is formed by the methylation of deoxyuridylate 748 Dihydrofolate reductase catalyzes the regeneration of tetrahydrofolate, a one-carbon carrier 749 Several valuable anticancer drugs block the synthesis of thymidylate 749 25.4 Key Steps in Nucleotide Biosynthesis Are Regulated by Feedback Inhibition 750 Pyrimidine biosynthesis is regulated by aspartate transcarbamoylase 751 The synthesis of purine nucleotides is controlled by feedback inhibition at several sites 751 The synthesis of deoxyribonucleotides is controlled by the regulation of ribonucleotide reductase 752 25.5 Disruptions in Nucleotide Metabolism Can Cause Pathological Conditions 752 The loss of adenosine deaminase activity results in severe combined immunodeficiency 752 Gout is induced by high serum levels of urate 753 Lesch–Nyhan syndrome is a dramatic consequence of mutations in a salvage-pathway enzyme 754 Folic acid deficiency promotes birth defects such as spina bifida 755 Chapter 26 The Biosynthesis of Membrane Lipids and Steroids 759 26.1 Phosphatidate Is a Common Intermediate in the Synthesis of Phospholipids and Triacylglycerols 760 The synthesis of phospholipids requires an activated intermediate 761 Sphingolipids are synthesized from ceramide 763 Gangliosides are carbohydrate-rich sphingolipids that contain acidic sugars 764 Sphingolipids confer diversity on lipid structure and function 765 Respiratory distress syndrome and Tay–Sachs disease result from the disruption of lipid metabolism 765 Phosphatiditic acid phosphatase is a key regulatory enzyme in lipid metabolism 766 26.2 Cholesterol Is Synthesized from Acetyl Coenzyme A in Three Stages 767 The synthesis of mevalonate, which is activated as isopentenyl pyrophosphate, initiates the synthesis of cholesterol 767 Squalene (C30) is synthesized from six molecules of isopentenyl pyrophosphate (C5) 768 Squalene cyclizes to form cholesterol 769 26.3 The Complex Regulation of Cholesterol Biosynthesis Takes Place at Several Levels 770 Lipoproteins transport cholesterol and triacylglycerols throughout the organism 773 The blood levels of certain lipoproteins can serve diagnostic purposes 774 Low-density lipoproteins play a central role in cholesterol metabolism 775 The absence of the LDL receptor leads to hypercholesterolemia and atherosclerosis 776 Mutations in the LDL receptor prevent LDL release and result in receptor destruction 777
xxviii Contents HDL appears to protect against arteriosclerosis 778 Metabolic adaptations in prolonged starvation The clinical management of cholesterol levels can be minimize protein degradation 808 understood at a biochemical level 779 27.6 Ethanol Alters Energy Metabolism in 26.4 Important Derivatives of Cholesterol the Liver 810 Include Bile Salts and Steroid Hormones 779 Ethanol metabolism leads to an excess of NADH 810 Letters identify the steroid rings and numbers Excess ethanol consumption disrupts vitamin identify the carbon atoms 781 metabolism 812 Steroids are hydroxylated by cytochrome P450 monooxygenases that use NADPH and O2 781 Chapter 28 DNA Replication,Repair,and The cytochrome P450 system is widespread and Recombination 819 performs a protective function 782 28.1 DNA Replication Proceeds by the Pregnenolone,a precursor of many other steroids,is Polymerization of Deoxyribonucleoside formed from cholesterol by cleavage of its side chain 783 Triphosphates Along a Template 820 Progesterone and corticosteroids are synthesized from pregnenolone 783 DNA polymerases require a template and a primer 820 Androgens and estrogens are synthesized from All DNA polymerases have structural features in common 821 pregnenolone 784 Vitamin D is derived from cholesterol by the Two bound metal ions participate in the ring-splitting activity of light 785 polymerase reaction 821 The specificity of replication is dictated by Chapter 27 The Integration of Metabolism 791 complementarity of shape between bases 822 27.1 Caloric Homeostasis Is a Means of An RNA primer synthesized by primase enables DNA synthesis to begin 823 Regulating Body Weight 792 One strand of DNA is made continuously,whereas 27.2 The Brain Plays a Key Role in Caloric the other strand is synthesized in fragments 823 Homeostasis 794 DNA ligase joins ends of DNA in duplex regions 824 Signals from the gastrointestinal tract induce feelings The separation of DNA strands requires specific of satiety 794 helicases and ATP hydrolysis 824 Leptin and insulin regulate long-term control 28.2 DNA Unwinding and Supercoiling Are over caloric homeostasis 795 Controlled by Topoisomerases 825 Leptin is one of several hormones secreted by The linking number of DNA,a topological property. adipose tissue 796 determines the degree of supercoiling 826 Leptin resistance may be a contributing factor Topoisomerases prepare the double helix for to obesity 797 unwinding 828 Dieting is used to combat obesity 797 Type I topoisomerases relax supercoiled structures 828 27.3 Diabetes Is a Common Metabolic Disease Type II topoisomerases can introduce negative Often Resulting from Obesity 798 supercoils through coupling to ATP hydrolysis 829 Insulin initiates a complex signal-transduction 28.3 DNA Replication Is Highly Coordinated 831 pathway in muscle 798 Metabolic syndrome often precedes type 2 diabetes DNA replication requires highly processive polymerases 831 800 The leading and lagging strands are synthesized Excess fatty acids in muscle modify metabolism 800 in a coordinated fashion 832 Insulin resistance in muscle facilitates pancreatic failure 801 DNA replication in Escherichia coli begins at a Metabolic derangements in type 1 diabetes result from unique site 834 insulin insufficiency and glucagon excess 802 DNA synthesis in eukaryotes is initiated at multiple sites 835 27.4 Exercise Beneficially Alters the Telomeres are unique structures at the ends of Biochemistry of Cells 803 linear chromosomes 836 Mitochondrial biogenesis is stimulated by muscular activity 804 Telomeres are replicated by telomerase,a specialized Fuel choice during exercise is determined by the polymerase that carries its own RNA template 837 intensity and duration of activity 805 28.4 Many Types of DNA Damage Can Be 27.5 Food Intake and Starvation Induce Repaired 837 Metabolic Changes 806 Errors can arise in DNA replication 837 The starved-fed cycle is the physiological response Bases can be damaged by oxidizing agents,alkylating to a fast 807 agents,and light 838
xxviii Contents HDL appears to protect against arteriosclerosis 778 The clinical management of cholesterol levels can be understood at a biochemical level 779 26.4 Important Derivatives of Cholesterol Include Bile Salts and Steroid Hormones 779 Letters identify the steroid rings and numbers identify the carbon atoms 781 Steroids are hydroxylated by cytochrome P450 monooxygenases that use NADPH and O2 781 The cytochrome P450 system is widespread and performs a protective function 782 Pregnenolone, a precursor of many other steroids, is formed from cholesterol by cleavage of its side chain 783 Progesterone and corticosteroids are synthesized from pregnenolone 783 Androgens and estrogens are synthesized from pregnenolone 784 Vitamin D is derived from cholesterol by the ring-splitting activity of light 785 Chapter 27 The Integration of Metabolism 791 27.1 Caloric Homeostasis Is a Means of Regulating Body Weight 792 27.2 The Brain Plays a Key Role in Caloric Homeostasis 794 Signals from the gastrointestinal tract induce feelings of satiety 794 Leptin and insulin regulate long-term control over caloric homeostasis 795 Leptin is one of several hormones secreted by adipose tissue 796 Leptin resistance may be a contributing factor to obesity 797 Dieting is used to combat obesity 797 27.3 Diabetes Is a Common Metabolic Disease Often Resulting from Obesity 798 Insulin initiates a complex signal-transduction pathway in muscle 798 Metabolic syndrome often precedes type 2 diabetes 800 Excess fatty acids in muscle modify metabolism 800 Insulin resistance in muscle facilitates pancreatic failure 801 Metabolic derangements in type 1 diabetes result from insulin insufficiency and glucagon excess 802 27.4 Exercise Beneficially Alters the Biochemistry of Cells 803 Mitochondrial biogenesis is stimulated by muscular activity 804 Fuel choice during exercise is determined by the intensity and duration of activity 805 27.5 Food Intake and Starvation Induce Metabolic Changes 806 The starved–fed cycle is the physiological response to a fast 807 Metabolic adaptations in prolonged starvation minimize protein degradation 808 27.6 Ethanol Alters Energy Metabolism in the Liver 810 Ethanol metabolism leads to an excess of NADH 810 Excess ethanol consumption disrupts vitamin metabolism 812 Chapter 28 DNA Replication, Repair, and Recombination 819 28.1 DNA Replication Proceeds by the Polymerization of Deoxyribonucleoside Triphosphates Along a Template 820 DNA polymerases require a template and a primer 820 All DNA polymerases have structural features in common 821 Two bound metal ions participate in the polymerase reaction 821 The specificity of replication is dictated by complementarity of shape between bases 822 An RNA primer synthesized by primase enables DNA synthesis to begin 823 One strand of DNA is made continuously, whereas the other strand is synthesized in fragments 823 DNA ligase joins ends of DNA in duplex regions 824 The separation of DNA strands requires specific helicases and ATP hydrolysis 824 28.2 DNA Unwinding and Supercoiling Are Controlled by Topoisomerases 825 The linking number of DNA, a topological property, determines the degree of supercoiling 826 Topoisomerases prepare the double helix for unwinding 828 Type I topoisomerases relax supercoiled structures 828 Type II topoisomerases can introduce negative supercoils through coupling to ATP hydrolysis 829 28.3 DNA Replication Is Highly Coordinated 831 DNA replication requires highly processive polymerases 831 The leading and lagging strands are synthesized in a coordinated fashion 832 DNA replication in Escherichia coli begins at a unique site 834 DNA synthesis in eukaryotes is initiated at multiple sites 835 Telomeres are unique structures at the ends of linear chromosomes 836 Telomeres are replicated by telomerase, a specialized polymerase that carries its own RNA template 837 28.4 Many Types of DNA Damage Can Be Repaired 837 Errors can arise in DNA replication 837 Bases can be damaged by oxidizing agents, alkylating agents, and light 838
Contents xxix DNA damage can be detected and repaired by a Enhancer sequences can stimulate transcription at variety of systems 839 start sites thousands of bases away 868 The presence of thymine instead of uracil in DNA 29.3 The Transcription Products of Eukaryotic permits the repair of deaminated cytosine 841 Polymerases Are Processed 869 Some genetic diseases are caused by the expansion RNA polymerase I produces three ribosomal RNAs 869 of repeats of three nucleotides 842 RNA polymerase III produces transfer RNA 870 Many cancers are caused by the defective repair of DNA 842 The product of RNA polymerase II,the pre-mRNA transcript,acquires a 5'cap and a 3'poly(A)tail 870 Many potential carcinogens can be detected by their Small regulatory RNAs are cleaved from larger mutagenic action on bacteria 843 precursors 872 28.5 DNA Recombination Plays Important Roles RNA editing changes the proteins encoded by mRNA 872 in Replication,Repair,and Other Processes 844 Sequences at the ends of introns specify splice sites RecA can initiate recombination by promoting strand in mRNA precursors 873 invasion 844 Splicing consists of two sequential transesterification Some recombination reactions proceed through reactions 874 Holliday-junction intermediates 845 Small nuclear RNAs in spliceosomes catalyze the splicing of mRNA precursors 875 Chapter 29 RNA Synthesis and Processing 851 Transcription and processing of mRNA are coupled 877 Mutations that affect pre-mRNA splicing cause disease 877 RNA synthesis comprises three stages:Initiation Most human pre-mRNAS can be spliced in alternative elongation,and termination 852 ways to yield different proteins 878 29.1 RNA Polymerases Catalyze Transcription 853 29.4 The Discovery of Catalytic RNA Was RNA chains are formed de novo and grow in the Revealing in Regard to Both Mechanism and 5'-to-3'direction 854 Evolution 879 RNA polymerases backtrack and correct errors 856 RNA polymerase binds to promoter sites on the DNA template to initiate transcription 856 Chapter 30 Protein Synthesis 887 Sigma subunits of RNA polymerase recognize promoter sites 857 30.1 Protein Synthesis Requires the Translation of Nucleotide Sequences into Amino Acid RNA polymerases must unwind the template Sequences 888 double helix for transcription to take place 858 Elongation takes place at transcription bubbles The synthesis of long proteins requires a low error frequency 888 that move along the DNA template 858 889 Sequences within the newly transcribed RNA signal Transfer RNA molecules have a common design termination 859 Some transfer RNA molecules recognize more than one codon because of wobble in base-pairing 891 Some messenger RNAs directly sense metabolite concentrations 860 30.2 Aminoacyl Transfer RNA Synthetases The rho protein helps to terminate the transcription Read the Genetic Code 893 of some genes 860 Amino acids are first activated by adenylation 893 Some antibiotics inhibit transcription 861 Aminoacyl-tRNA synthetases have highly discriminating Precursors of transfer and ribosomal RNA are amino acid activation sites 894 cleaved and chemically modified after transcription Proofreading by aminoacyl-tRNA synthetases increases in prokaryotes 863 the fidelity of protein synthesis 895 29.2 Transcription in Eukaryotes Is Highly Synthetases recognize various features of transfer RNA Regulated 864 molecules 896 Three types of RNA polymerase synthesize RNA in Aminoacyl-tRNA synthetases can be divided into two eukaryotic cells 865 classes 897 Three common elements can be found in the RNA 30.3 The Ribosome Is the Site of Protein polymerase II promoter region 866 Synthesis 897 The TFIID protein complex initiates the assembly of Ribosomal RNAs(5S,16S,and 23S rRNA)play a central the active transcription complex 867 role in protein synthesis 898 Multiple transcription factors interact with eukaryotic Ribosomes have three tRNA-binding sites that bridge promoters 868 the 30s and 50s subunits 900
Contents xxix DNA damage can be detected and repaired by a variety of systems 839 The presence of thymine instead of uracil in DNA permits the repair of deaminated cytosine 841 Some genetic diseases are caused by the expansion of repeats of three nucleotides 842 Many cancers are caused by the defective repair of DNA 842 Many potential carcinogens can be detected by their mutagenic action on bacteria 843 28.5 DNA Recombination Plays Important Roles in Replication, Repair, and Other Processes 844 RecA can initiate recombination by promoting strand invasion 844 Some recombination reactions proceed through Holliday-junction intermediates 845 Chapter 29 RNA Synthesis and Processing 851 RNA synthesis comprises three stages: Initiation, elongation, and termination 852 29.1 RNA Polymerases Catalyze Transcription 853 RNA chains are formed de novo and grow in the 59-to-39 direction 854 RNA polymerases backtrack and correct errors 856 RNA polymerase binds to promoter sites on the DNA template to initiate transcription 856 Sigma subunits of RNA polymerase recognize promoter sites 857 RNA polymerases must unwind the template double helix for transcription to take place 858 Elongation takes place at transcription bubbles that move along the DNA template 858 Sequences within the newly transcribed RNA signal termination 859 Some messenger RNAs directly sense metabolite concentrations 860 The rho protein helps to terminate the transcription of some genes 860 Some antibiotics inhibit transcription 861 Precursors of transfer and ribosomal RNA are cleaved and chemically modified after transcription in prokaryotes 863 29.2 Transcription in Eukaryotes Is Highly Regulated 864 Three types of RNA polymerase synthesize RNA in eukaryotic cells 865 Three common elements can be found in the RNA polymerase II promoter region 866 The TFIID protein complex initiates the assembly of the active transcription complex 867 Multiple transcription factors interact with eukaryotic promoters 868 Enhancer sequences can stimulate transcription at start sites thousands of bases away 868 29.3 The Transcription Products of Eukaryotic Polymerases Are Processed 869 RNA polymerase I produces three ribosomal RNAs 869 RNA polymerase III produces transfer RNA 870 The product of RNA polymerase II, the pre-mRNA transcript, acquires a 59 cap and a 39 poly(A) tail 870 Small regulatory RNAs are cleaved from larger precursors 872 RNA editing changes the proteins encoded by mRNA 872 Sequences at the ends of introns specify splice sites in mRNA precursors 873 Splicing consists of two sequential transesterification reactions 874 Small nuclear RNAs in spliceosomes catalyze the splicing of mRNA precursors 875 Transcription and processing of mRNA are coupled 877 Mutations that affect pre-mRNA splicing cause disease 877 Most human pre-mRNAS can be spliced in alternative ways to yield different proteins 878 29.4 The Discovery of Catalytic RNA Was Revealing in Regard to Both Mechanism and Evolution 879 Chapter 30 Protein Synthesis 887 30.1 Protein Synthesis Requires the Translation of Nucleotide Sequences into Amino Acid Sequences 888 The synthesis of long proteins requires a low error frequency 888 Transfer RNA molecules have a common design 889 Some transfer RNA molecules recognize more than one codon because of wobble in base-pairing 891 30.2 Aminoacyl Transfer RNA Synthetases Read the Genetic Code 893 Amino acids are first activated by adenylation 893 Aminoacyl-tRNA synthetases have highly discriminating amino acid activation sites 894 Proofreading by aminoacyl-tRNA synthetases increases the fidelity of protein synthesis 895 Synthetases recognize various features of transfer RNA molecules 896 Aminoacyl-tRNA synthetases can be divided into two classes 897 30.3 The Ribosome Is the Site of Protein Synthesis 897 Ribosomal RNAs (5S, 16S, and 23S rRNA) play a central role in protein synthesis 898 Ribosomes have three tRNA-binding sites that bridge the 30s and 50s subunits 900
XXX Contents The start signal is usually AUG preceded by several 31.3 Regulatory Circuits Can Result in Switching bases that pair with 16S rRNA 900 Between Patterns of Gene Expression 928 Bacterial protein synthesis is initiated by Lambda repressor regulates its own expression 928 formylmethionyl transfer RNA 901 A circuit based on lambda repressor and Cro form Formylmethionyl-tRNAris placed in the P site of a genetic switch 929 the ribosome in the formation of the 70S Many prokaryotic cells release chemical signals that initiation complex 902 regulate gene expression in other cells 929 Elongation factors deliver aminoacyl-tRNA to the 902 Biofilms are complex communities of prokaryotes 930 ribosome Peptidyl transferase catalyzes peptide-bond 31.4 Gene Expression Can Be Controlled at synthesis 903 Posttranscriptional Levels 931 The formation of a peptide bond is followed by the Attenuation is a prokaryotic mechanism for regulating GTP-driven translocation of tRNAs and mRNA 904 transcription through the modulation of nascent RNA secondary structure 931 Protein synthesis is terminated by release factors that read stop codons 906 30.4 Eukaryotic Protein Synthesis Differs Chapter 32 The Control of Gene Expression 937 from Prokaryotic Protein Synthesis Primarily in Eukaryotes in Translation Initiation 907 32.1 Eukaryotic DNA Is Organized into Mutations in initiation factor 2 cause a curious Chromatin 938 pathological condition 908 Nucleosomes are complexes of DNA and histones 939 30.5 A Variety of Antibiotics and Toxins Can DNA wraps around histone octamers to form Inhibit Protein Synthesis 909 nucleosomes 939 Some antibiotics inhibit protein synthesis 909 32.2 Transcription Factors Bind DNA and Diphtheria toxin blocks protein synthesis in eukaryotes Regulate Transcription Initiation 941 by inhibiting translocation 910 A range of DNA-binding structures are employed Ricin fatally modifies 28S ribosomal RNA 911 by eukaryotic DNA-binding proteins 941 30.6 Ribosomes Bound to the Endoplasmic Activation domains interact with other proteins 942 Reticulum Manufacture Secretory and Multiple transcription factors interact with eukaryotic Membrane Proteins 911 regulatory regions 943 Signal sequences mark proteins for translocation across Enhancers can stimulate transcription in specific the endoplasmic reticulum membrane 911 cell types 943 Transport vesicles carry cargo proteins to their final Induced pluripotent stem cells can be generated by destination 913 introducing four transcription factors into differentiated cells 944 32.3 The Control of Gene Expression Can Chapter 31 The Control of Gene Expression Require Chromatin Remodeling 944 in Prokaryotes 921 The methylation of DNA can alter patterns of gene 31.1 Many DNA-Binding Proteins Recognize expression 945 Specific DNA Sequences 922 Steroids and related hydrophobic molecules pass The helix-turn-helix motif is common to many through membranes and bind to DNA-binding receptors 946 prokaryotic DNA-binding proteins 923 Nuclear hormone receptors regulate transcription by 31.2 Prokaryotic DNA-Binding Proteins Bind recruiting coactivators to the transcription complex 946 Specifically to Regulatory Sites in Operons 923 Steroid-hormone receptors are targets for drugs 948 An operon consists of regulatory elements and Chromatin structure is modulated through covalent protein-encoding genes 924 modifications of histone tails 949 The lac repressor protein in the absence of lactose Histone deacetylases contribute to transcriptional binds to the operator and blocks transcription 925 repression 950 Ligand binding can induce structural changes in 32.4 Eukaryotic Gene Expression Can Be regulatory proteins 926 Controlled at Posttranscriptional Levels 951 The operon is a common regulatory unit in Genes associated with iron metabolism are prokaryotes 926 translationally regulated in animals 951 Transcription can be stimulated by proteins that Small RNAs regulate the expression of many contact RNA polymerase 927 eukaryotic genes 953
xxx Contents The start signal is usually AUG preceded by several bases that pair with 16S rRNA 900 Bacterial protein synthesis is initiated by formylmethionyl transfer RNA 901 Formylmethionyl-tRNAf is placed in the P site of the ribosome in the formation of the 70S initiation complex 902 Elongation factors deliver aminoacyl-tRNA to the ribosome 902 Peptidyl transferase catalyzes peptide-bond synthesis 903 The formation of a peptide bond is followed by the GTP-driven translocation of tRNAs and mRNA 904 Protein synthesis is terminated by release factors that read stop codons 906 30.4 Eukaryotic Protein Synthesis Differs from Prokaryotic Protein Synthesis Primarily in Translation Initiation 907 Mutations in initiation factor 2 cause a curious pathological condition 908 30.5 A Variety of Antibiotics and Toxins Can Inhibit Protein Synthesis 909 Some antibiotics inhibit protein synthesis 909 Diphtheria toxin blocks protein synthesis in eukaryotes by inhibiting translocation 910 Ricin fatally modifies 28S ribosomal RNA 911 30.6 Ribosomes Bound to the Endoplasmic Reticulum Manufacture Secretory and Membrane Proteins 911 Signal sequences mark proteins for translocation across the endoplasmic reticulum membrane 911 Transport vesicles carry cargo proteins to their final destination 913 Chapter 31 The Control of Gene Expression in Prokaryotes 921 31.1 Many DNA-Binding Proteins Recognize Specific DNA Sequences 922 The helix-turn-helix motif is common to many prokaryotic DNA-binding proteins 923 31.2 Prokaryotic DNA-Binding Proteins Bind Specifically to Regulatory Sites in Operons 923 An operon consists of regulatory elements and protein-encoding genes 924 The lac repressor protein in the absence of lactose binds to the operator and blocks transcription 925 Ligand binding can induce structural changes in regulatory proteins 926 The operon is a common regulatory unit in prokaryotes 926 Transcription can be stimulated by proteins that contact RNA polymerase 927 31.3 Regulatory Circuits Can Result in Switching Between Patterns of Gene Expression 928 Lambda repressor regulates its own expression 928 A circuit based on lambda repressor and Cro form a genetic switch 929 Many prokaryotic cells release chemical signals that regulate gene expression in other cells 929 Biofilms are complex communities of prokaryotes 930 31.4 Gene Expression Can Be Controlled at Posttranscriptional Levels 931 Attenuation is a prokaryotic mechanism for regulating transcription through the modulation of nascent RNA secondary structure 931 Chapter 32 The Control of Gene Expression in Eukaryotes 937 32.1 Eukaryotic DNA Is Organized into Chromatin 938 Nucleosomes are complexes of DNA and histones 939 DNA wraps around histone octamers to form nucleosomes 939 32.2 Transcription Factors Bind DNA and Regulate Transcription Initiation 941 A range of DNA-binding structures are employed by eukaryotic DNA-binding proteins 941 Activation domains interact with other proteins 942 Multiple transcription factors interact with eukaryotic regulatory regions 943 Enhancers can stimulate transcription in specific cell types 943 Induced pluripotent stem cells can be generated by introducing four transcription factors into differentiated cells 944 32.3 The Control of Gene Expression Can Require Chromatin Remodeling 944 The methylation of DNA can alter patterns of gene expression 945 Steroids and related hydrophobic molecules pass through membranes and bind to DNA-binding receptors 946 Nuclear hormone receptors regulate transcription by recruiting coactivators to the transcription complex 946 Steroid-hormone receptors are targets for drugs 948 Chromatin structure is modulated through covalent modifications of histone tails 949 Histone deacetylases contribute to transcriptional repression 950 32.4 Eukaryotic Gene Expression Can Be Controlled at Posttranscriptional Levels 951 Genes associated with iron metabolism are translationally regulated in animals 951 Small RNAs regulate the expression of many eukaryotic genes 953
Contents xxxi Part IV RESPONDING TO 34.1 Antibodies Possess Distinct ENVIRONMENTAL CHANGES Antigen-Binding and Effector Units 981 34.2 Antibodies Bind Specific Molecules Chapter 33 Sensory Systems 957 Through Hypervariable Loops 983 33.1 A Wide Variety of Organic Compounds The immunoglobulin fold consists of a beta-sandwich framework with hypervariable loops 984 Are Detected by Olfaction 958 X-ray analyses have revealed how antibodies Olfaction is mediated by an enormous family of bind antigens 984 seven-transmembrane-helix receptors 958 Large antigens bind antibodies with numerous Odorants are decoded by a combinatorial mechanism 960 interactions 986 33.2 Taste Is a Combination of Senses That 34.3 Diversity Is Generated by Gene Function by Different Mechanisms 962 Rearrangements 987 Sequencing of the human genome led to the discovery of a large family of 7TM bitter receptors J(joining)genes and D(diversity)genes increase 963 antibody diversity 987 A heterodimeric 7TM receptor responds to sweet More than 10 antibodies can be formed by compounds 964 combinatorial association and somatic mutation 988 Umami,the taste of glutamate and aspartate,is The oligomerization of antibodies expressed on the mediated by a heterodimeric receptor related to surfaces of immature B cells triggers antibody secretion 989 the sweet receptor 965 Different classes of antibodies are formed by Salty tastes are detected primarily by the passage of the hopping of VH genes 990 sodium ions through channels 965 Sour tastes arise from the effects of hydrogen 34.4 Major-Histocompatibility-Complex ions(acids)on channels 965 Proteins Present Peptide Antigens on Cell Surfaces for Recognition by T-Cell Receptors 99 33.3 Photoreceptor Molecules in the Eye Detect Visible Light Peptides presented by MHC proteins occupy a deep 966 groove flanked by alpha helices 992 Rhodopsin,a specialized 7TM receptor,absorbs visible light T-cell receptors are antibody-like proteins 966 containing variable and constant regions 994 Light absorption induces a specific isomerization of bound 11-cis-retinal 967 CD8 on cytotoxic T cells acts in concert with T-cell receptors 994 Light-induced lowering of the calcium level Helper T cells stimulate cells that display foreign coordinates recovery 968 peptides bound to class II MHC proteins 996 Color vision is mediated by three cone receptors Helper T cells rely on the T-cell receptor and CD4 to that are homologs of rhodopsin 969 recognize foreign peptides on antigen-presenting cells 996 Rearrangements in the genes for the green and 998 red pigments lead to“color blindness'” 970 MHC proteins are highly diverse Human immunodeficiency viruses subvert the 33.4 Hearing Depends on the Speedy immune system by destroying helper T cells 999 Detection of Mechanical Stimuli 971 34.5 The Immune System Contributes to the Hair cells use a connected bundle of stereocilia to Prevention and the Development of Human detect tiny motions 971 Diseases 1000 Mechanosensory channels have been identified in Drosophila and vertebrates 972 T cells are subjected to positive and negative selection in the thymus 1000 33.5 Touch Includes the Sensing of Pressure, Autoimmune diseases result from the generation Temperature,and Other Factors 973 of immune responses against self-antigens 1001 Studies of capsaicin reveal a receptor for sensing The immune system plays a role in cancer prevention 1001 high temperatures and other painful stimuli 973 Vaccines are a powerful means to prevent and More sensory systems remain to be studied 974 eradicate disease 1002 Chapter 34 The Immune System 977 Chapter 35 Molecular Motors 1007 Innate immunity is an evolutionarily ancient 35.1 Most Molecular-Motor Proteins Are defense system 978 Members of the P-Loop NTPase Superfamily 1008 The adaptive immune system responds by using Molecular motors are generally oligomeric proteins the principles of evolution 979 with an ATPase core and an extended structure 1008
Contents xxxi Part IV RESPONDING TO ENVIRONMENTAL CHANGES Chapter 33 Sensory Systems 957 33.1 A Wide Variety of Organic Compounds Are Detected by Olfaction 958 Olfaction is mediated by an enormous family of seven-transmembrane-helix receptors 958 Odorants are decoded by a combinatorial mechanism 960 33.2 Taste Is a Combination of Senses That Function by Different Mechanisms 962 Sequencing of the human genome led to the discovery of a large family of 7TM bitter receptors 963 A heterodimeric 7TM receptor responds to sweet compounds 964 Umami, the taste of glutamate and aspartate, is mediated by a heterodimeric receptor related to the sweet receptor 965 Salty tastes are detected primarily by the passage of sodium ions through channels 965 Sour tastes arise from the effects of hydrogen ions (acids) on channels 965 33.3 Photoreceptor Molecules in the Eye Detect Visible Light 966 Rhodopsin, a specialized 7TM receptor, absorbs visible light 966 Light absorption induces a specific isomerization of bound 11-cis-retinal 967 Light-induced lowering of the calcium level coordinates recovery 968 Color vision is mediated by three cone receptors that are homologs of rhodopsin 969 Rearrangements in the genes for the green and red pigments lead to “color blindness” 970 33.4 Hearing Depends on the Speedy Detection of Mechanical Stimuli 971 Hair cells use a connected bundle of stereocilia to detect tiny motions 971 Mechanosensory channels have been identified in Drosophila and vertebrates 972 33.5 Touch Includes the Sensing of Pressure, Temperature, and Other Factors 973 Studies of capsaicin reveal a receptor for sensing high temperatures and other painful stimuli 973 More sensory systems remain to be studied 974 Chapter 34 The Immune System 977 Innate immunity is an evolutionarily ancient defense system 978 The adaptive immune system responds by using the principles of evolution 979 34.1 Antibodies Possess Distinct Antigen-Binding and Effector Units 981 34.2 Antibodies Bind Specific Molecules Through Hypervariable Loops 983 The immunoglobulin fold consists of a beta-sandwich framework with hypervariable loops 984 X-ray analyses have revealed how antibodies bind antigens 984 Large antigens bind antibodies with numerous interactions 986 34.3 Diversity Is Generated by Gene Rearrangements 987 J (joining) genes and D (diversity) genes increase antibody diversity 987 More than 108 antibodies can be formed by combinatorial association and somatic mutation 988 The oligomerization of antibodies expressed on the surfaces of immature B cells triggers antibody secretion 989 Different classes of antibodies are formed by the hopping of VH genes 990 34.4 Major-Histocompatibility-Complex Proteins Present Peptide Antigens on Cell Surfaces for Recognition by T-Cell Receptors 991 Peptides presented by MHC proteins occupy a deep groove flanked by alpha helices 992 T-cell receptors are antibody-like proteins containing variable and constant regions 994 CD8 on cytotoxic T cells acts in concert with T-cell receptors 994 Helper T cells stimulate cells that display foreign peptides bound to class II MHC proteins 996 Helper T cells rely on the T-cell receptor and CD4 to recognize foreign peptides on antigen-presenting cells 996 MHC proteins are highly diverse 998 Human immunodeficiency viruses subvert the immune system by destroying helper T cells 999 34.5 The Immune System Contributes to the Prevention and the Development of Human Diseases 1000 T cells are subjected to positive and negative selection in the thymus 1000 Autoimmune diseases result from the generation of immune responses against self-antigens 1001 The immune system plays a role in cancer prevention 1001 Vaccines are a powerful means to prevent and eradicate disease 1002 Chapter 35 Molecular Motors 1007 35.1 Most Molecular-Motor Proteins Are Members of the P-Loop NTPase Superfamily 1008 Molecular motors are generally oligomeric proteins with an ATPase core and an extended structure 1008