《生物化学》课程教学资源（书籍文献）Biochemistry, EIGHTH EDITION 2015, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto, Jr. Lubert Stryer.pdf_P21-P25

Contents xxiii NAD1 is regenerated from the metabolism of pyruvate 462 Fermentations provide usable energy in the absence of oxygen 464 The binding site for NAD1 is similar in many dehydrogenases 465 Fructose is converted into glycolytic intermediates by fructokinase 465 Excessive fructose consumption can lead to pathological conditions 466 Galactose is converted into glucose 6-phosphate 466 Many adults are intolerant of milk because they are deficient in lactase 467 Galactose is highly toxic if the transferase is missing 468 16.2 The Glycolytic Pathway Is Tightly Controlled 469 Glycolysis in muscle is regulated to meet the need for ATP 469 The regulation of glycolysis in the liver illustrates the biochemical versatility of the liver 472 A family of transporters enables glucose to enter and leave animal cells 473 Aerobic glycolysis is a property of rapidly growing cells 474 Cancer and endurance training affect glycolysis in a similar fashion 476 16.3 Glucose Can Be Synthesized from Noncarbohydrate Precursors 476 Gluconeogenesis is not a reversal of glycolysis 478 The conversion of pyruvate into phosphoenolpyruvate begins with the formation of oxaloacetate 478 Oxaloacetate is shuttled into the cytoplasm and converted into phosphoenolpyruvate 480 The conversion of fructose 1,6-bisphosphate into fructose 6-phosphate and orthophosphate is an irreversible step 480 The generation of free glucose is an important control point 481 Six high-transfer-potential phosphoryl groups are spent in synthesizing glucose from pyruvate 481 16.4 Gluconeogenesis and Glycolysis Are Reciprocally Regulated 482 Energy charge determines whether glycolysis or gluconeogenesis will be most active 482 The balance between glycolysis and gluconeogenesis in the liver is sensitive to blood-glucose concentration 483 Substrate cycles amplify metabolic signals and produce heat 485 Lactate and alanine formed by contracting muscle are used by other organs 485 Glycolysis and gluconeogenesis are evolutionarily intertwined 487 CHAPTER 17 The Citric Acid Cycle 495 The citric acid cycle harvests high-energy electrons 496 17.1 The Pyruvate Dehydrogenase Complex Links Glycolysis to the Citric Acid Cycle 497 Mechanism: The synthesis of acetyl coenzyme A from pyruvate requires three enzymes and five coenzymes 498 Flexible linkages allow lipoamide to move between different active sites 500 17.2 The Citric Acid Cycle Oxidizes Two-Carbon Units 501 Citrate synthase forms citrate from oxaloacetate and acetyl coenzyme A 502 Mechanism: The mechanism of citrate synthase prevents undesirable reactions 502 Citrate is isomerized into isocitrate 504 Isocitrate is oxidized and decarboxylated to alphaketoglutarate 504 Succinyl coenzyme A is formed by the oxidative decarboxylation of alpha-ketoglutarate 505 A compound with high phosphoryl-transfer potential is generated from succinyl coenzyme A 505 Mechanism: Succinyl coenzyme A synthetase transforms types of biochemical energy 506 Oxaloacetate is regenerated by the oxidation of succinate 507 The citric acid cycle produces high-transfer-potential electrons, ATP, and CO2 508 17.3 Entry to the Citric Acid Cycle and Metabolism Through It Are Controlled 510 The pyruvate dehydrogenase complex is regulated allosterically and by reversible phosphorylation 511 The citric acid cycle is controlled at several points 512 Defects in the citric acid cycle contribute to the development of cancer 513 17.4 The Citric Acid Cycle Is a Source of Biosynthetic Precursors 514 The citric acid cycle must be capable of being rapidly replenished 514 The disruption of pyruvate metabolism is the cause of beriberi and poisoning by mercury and arsenic 515 The citric acid cycle may have evolved from preexisting pathways 516 17.5 The Glyoxylate Cycle Enables Plants and Bacteria to Grow on Acetate 516 CHAPTER 18 Oxidative Phosphorylation 523 18.1 Eukaryotic Oxidative Phosphorylation Takes Place in Mitochondria 524 Mitochondria are bounded by a double membrane 524 Mitochondria are the result of an endosymbiotic event 525 18.2 Oxidative Phosphorylation Depends on Electron Transfer 526 The electron-transfer potential of an electron is measured as redox potential 526 A 1.14-volt potential difference between NADH and molecular oxygen drives electron transport through the chain and favors the formation of a proton gradient 528 18.3 The Respiratory Chain Consists of Four Complexes: Three Proton Pumps and a Physical Link to the Citric Acid Cycle 529 Iron–sulfur clusters are common components of the electron transport chain 531 CHAPTER 17 The Citric Acid Cycle 495 CHAPTER 18 Oxidative Phosphorylation 523

xxiv Contents The high-potential electrons of NADH enter the respiratory chain at NADH-Q oxidoreductase 532 Ubiquinol is the entry point for electrons from FADH2 of flavoproteins 533 Electrons flow from ubiquinol to cytochrome c through Q-cytochrome c oxidoreductase 533 The Q cycle funnels electrons from a two-electron carrier to a one-electron carrier and pumps protons 535 Cytochrome c oxidase catalyzes the reduction of molecular oxygen to water 535 Toxic derivatives of molecular oxygen such as superoxide radicals are scavenged by protective enzymes 538 Electrons can be transferred between groups that are not in contact 540 The conformation of cytochrome c has remained essentially constant for more than a billion years 541 18.4 A Proton Gradient Powers the Synthesis of ATP 541 ATP synthase is composed of a proton-conducting unit and a catalytic unit 543 Proton flow through ATP synthase leads to the release of tightly bound ATP: The binding-change mechanism 544 Rotational catalysis is the world’s smallest molecular motor 546 Proton flow around the c ring powers ATP synthesis 546 ATP synthase and G proteins have several common features 548 18.5 Many Shuttles Allow Movement Across Mitochondrial Membranes 549 Electrons from cytoplasmic NADH enter mitochondria by shuttles 549 The entry of ADP into mitochondria is coupled to the exit of ATP by ATP-ADP translocase 550 Mitochondrial transporters for metabolites have a common tripartite structure 551 18.6 The Regulation of Cellular Respiration Is Governed Primarily by the Need for ATP 552 The complete oxidation of glucose yields about 30 molecules of ATP 552 The rate of oxidative phosphorylation is determined by the need for ATP 553 ATP synthase can be regulated 554 Regulated uncoupling leads to the generation of heat 554 Oxidative phosphorylation can be inhibited at many stages 556 Mitochondrial diseases are being discovered 557 Mitochondria play a key role in apoptosis 557 Power transmission by proton gradients is a central motif of bioenergetics 558 CHAPTER 19 The Light Reactions of Photosynthesis 565 Photosynthesis converts light energy into chemical energy 566 19.1 Photosynthesis Takes Place in Chloroplasts 567 The primary events of photosynthesis take place in thylakoid membranes 567 Chloroplasts arose from an endosymbiotic event 568 19.2 Light Absorption by Chlorophyll Induces Electron Transfer 568 A special pair of chlorophylls initiate charge separation 569 Cyclic electron flow reduces the cytochrome of the reaction center 572 19.3 Two Photosystems Generate a Proton Gradient and NADPH in Oxygenic Photosynthesis 572 Photosystem II transfers electrons from water to plastoquinone and generates a proton gradient 572 Cytochrome bf links photosystem II to photosystem I 575 Photosystem I uses light energy to generate reduced ferredoxin, a powerful reductant 575 Ferredoxin–NADP1 reductase converts NADP1 into NADPH 576 19.4 A Proton Gradient across the Thylakoid Membrane Drives ATP Synthesis 578 The ATP synthase of chloroplasts closely resembles those of mitochondria and prokaryotes 578 The activity of chloroplast ATP synthase is regulated 579 Cyclic electron flow through photosystem I leads to the production of ATP instead of NADPH 580 The absorption of eight photons yields one O2, two NADPH, and three ATP molecules 581 19.5 Accessory Pigments Funnel Energy into Reaction Centers 581 Resonance energy transfer allows energy to move from the site of initial absorbance to the reaction center 582 The components of photosynthesis are highly organized 583 Many herbicides inhibit the light reactions of photosynthesis 584 19.6 The Ability to Convert Light into Chemical Energy Is Ancient 584 Artificial photosynthetic systems may provide clean, renewable energy 585 CHAPTER 20 The Calvin Cycle and the Pentose Phosphate Pathway 589 20.1 The Calvin Cycle Synthesizes Hexoses from Carbon Dioxide and Water 590 Carbon dioxide reacts with ribulose 1,5-bisphosphate to form two molecules of 3-phosphoglycerate 591 Rubisco activity depends on magnesium and carbamate 592 Rubisco activase is essential for rubisco activity 593 Rubisco also catalyzes a wasteful oxygenase reaction: Catalytic imperfection 593 Hexose phosphates are made from phosphoglycerate, and ribulose 1,5-bisphosphate is regenerated 594 Three ATP and two NADPH molecules are used to bring carbon dioxide to the level of a hexose 597 Starch and sucrose are the major carbohydrate stores in plants 597 20.2 The Activity of the Calvin Cycle Depends on Environmental Conditions 598 CHAPTER 19 The Light Reactions of Photosynthesis 565 CHAPTER 20 The Calvin Cycle and the Pentose Phosphate Pathway 589

Contents xxv Rubisco is activated by light-driven changes in proton and magnesium ion concentrations 598 Thioredoxin plays a key role in regulating the Calvin cycle 599 The C4 pathway of tropical plants accelerates photosynthesis by concentrating carbon dioxide 599 Crassulacean acid metabolism permits growth in arid ecosystems 601 20.3 The Pentose Phosphate Pathway Generates NADPH and Synthesizes Five-Carbon Sugars 601 Two molecules of NADPH are generated in the conversion of glucose 6-phosphate into ribulose 5-phosphate 602 The pentose phosphate pathway and glycolysis are linked by transketolase and transaldolase 602 Mechanism: Transketolase and transaldolase stabilize carbanionic intermediates by different mechanisms 605 20.4 The Metabolism of Glucose 6-Phosphate by the Pentose Phosphate Pathway Is Coordinated with Glycolysis 607 The rate of the pentose phosphate pathway is controlled by the level of NADP1 607 The flow of glucose 6-phosphate depends on the need for NADPH, ribose 5-phosphate, and ATP 608 The pentose phosphate pathway is required for rapid cell growth 610 Through the looking-glass: The Calvin cycle and the pentose phosphate pathway are mirror images 610 20.5 Glucose 6-Phosphate Dehydrogenase Plays a Key Role in Protection Against Reactive Oxygen Species 610 Glucose 6-phosphate dehydrogenase deficiency causes a drug-induced hemolytic anemia 610 A deficiency of glucose 6-phosphate dehydrogenase confers an evolutionary advantage in some circumstances 612 CHAPTER 21 Glycogen Metabolism 617 Glycogen metabolism is the regulated release and storage of glucose 618 21.1 Glycogen Breakdown Requires the Interplay of Several Enzymes 619 Phosphorylase catalyzes the phosphorolytic cleavage of glycogen to release glucose 1-phosphate 619 Mechanism: Pyridoxal phosphate participates in the phosphorolytic cleavage of glycogen 620 A debranching enzyme also is needed for the breakdown of glycogen 621 Phosphoglucomutase converts glucose 1-phosphate into glucose 6-phosphate 622 The liver contains glucose 6-phosphatase, a hydrolytic enzyme absent from muscle 622 21.2 Phosphorylase Is Regulated by Allosteric Interactions and Reversible Phosphorylation 623 Liver phosphorylase produces glucose for use by other tissues 623 Muscle phosphorylase is regulated by the intracellular energy charge 625 Biochemical characteristics of muscle fiber types differ 625 Phosphorylation promotes the conversion of phosphorylase b to phosphorylase a 626 Phosphorylase kinase is activated by phosphorylation and calcium ions 626 21.3 Epinephrine and Glucagon Signal the Need for Glycogen Breakdown 627 G proteins transmit the signal for the initiation of glycogen breakdown 627 Glycogen breakdown must be rapidly turned off when necessary 629 The regulation of glycogen phosphorylase became more sophisticated as the enzyme evolved 629 21.4 Glycogen Is Synthesized and Degraded by Different Pathways 630 UDP-glucose is an activated form of glucose 630 Glycogen synthase catalyzes the transfer of glucose from UDP-glucose to a growing chain 630 A branching enzyme forms a-1,6 linkages 631 Glycogen synthase is the key regulatory enzyme in glycogen synthesis 632 Glycogen is an efficient storage form of glucose 632 21.5 Glycogen Breakdown and Synthesis Are Reciprocally Regulated 632 Protein phosphatase 1 reverses the regulatory effects of kinases on glycogen metabolism 633 Insulin stimulates glycogen synthesis by inactivating glycogen synthase kinase 635 Glycogen metabolism in the liver regulates the blood-glucose level 635 A biochemical understanding of glycogen-storage diseases is possible 637 CHAPTER 22 Fatty Acid Metabolism 643 Fatty acid degradation and synthesis mirror each other in their chemical reactions 644 22.1 Triacylglycerols Are Highly Concentrated Energy Stores 645 Dietary lipids are digested by pancreatic lipases 645 Dietary lipids are transported in chylomicrons 646 22.2 The Use of Fatty Acids as Fuel Requires Three Stages of Processing 647 Triacylglycerols are hydrolyzed by hormonestimulated lipases 647 Free fatty acids and glycerol are released into the blood 648 Fatty acids are linked to coenzyme A before they are oxidized 648 Carnitine carries long-chain activated fatty acids into the mitochondrial matrix 649 Acetyl CoA, NADH, and FADH2 are generated in each round of fatty acid oxidation 650 CHAPTER 21 Glycogen Metabolism 617 CHAPTER 22 Fatty Acid Metabolism 643

xxvi Contents 1b6oebioEApnodpmmiaeyied 652 23.2 Protein Tumover Is Tightly Regulated 22.3 Unsaturated and Odd-Chain Fatty Acids The tags pr ed proteins 685 Require Additional Steps for Degradation 652 and ther 686 652 prokaryotic counterparts Protein degradationcan be used to regulate biological 687 thiolysis step 654 23.3 The First Step in Amino Acid Degradation Vitamin B2 containsa corrin ring and a cobalt atom 654 Is the Removal of Nitrogen 687 Fatty acids are also oxidized in on ofh 687 Ketone bodies are formed from acetylCoA when fat intermediates in aminotransferases 689 predominates 65 Aspartate aminotransferase is an archetypal pyridoxal- are a m fueli ne t nas 690 4。 a diagnostic function 691 661 22.4 Fatty Acids Are Synthesized by Fatty Acid 601 Synthase 661 e and threonine can be dire ectly dean 692 raded by different to the liver ced and de里i 692 661 23.4 Ammonium lon Is Converted into Urea in Most Terrestrial Vertebrates 693 662 are attached to an The urea cycle begins with the formation of carbamoyl 693 Carb yme for urea sythe tase isthe key regulatory 694 662 Carbamoyl phosphate 694 complex in anir 696 ated to 666 ymes in other metabolic pathway 696 607 DPH for fatty acid synthesis Jrea is not the only means of disposing of excess nitrogen 23.5 Carbon Atoms of Degraded Amino Acids 22.5The ation and Unsaturation of Fatty Acids Emerge as Major Metabolic Intermediates 698 668 Membrane-bound enzymes generate unsaturated fatty acids 668 699 coderiv ompolyure 669 etate is an entry point into metabolism for theme:Polyketide and nonri aspartate and asparagine 700 670 700 Succinyl coenzyme A is a point of entry for several 670 onpolar amino acid 701 reulated by ondition 671 701 Acetyl CoA carboxylase is regulated by a variety of The branched-chain amin hormones cetate,or propionyl 701 or the degradation of CHAPTER 23 Protein Turnover and romatic amino acids 703 Amino Acid Catabolism 681 Can Disrupt 705 23.1 Proteins are Degraded to Amino Acids 682 Phenvlketonuria is one of the most digestion of dietary proter ns begins in the stomach disorders 706 68 2

xxvi Contents The complete oxidation of palmitate yields 106 molecules of ATP 652 22.3 Unsaturated and Odd-Chain Fatty Acids Require Additional Steps for Degradation 652 An isomerase and a reductase are required for the oxidation of unsaturated fatty acids 652 Odd-chain fatty acids yield propionyl CoA in the final thiolysis step 654 Vitamin B12 contains a corrin ring and a cobalt atom 654 Mechanism: Methylmalonyl CoA mutase catalyzes a rearrangement to form succinyl CoA 655 Fatty acids are also oxidized in peroxisomes 656 Ketone bodies are formed from acetyl CoA when fat breakdown predominates 657 Ketone bodies are a major fuel in some tissues 658 Animals cannot convert fatty acids into glucose 660 Some fatty acids may contribute to the development of pathological conditions 661 22.4 Fatty Acids Are Synthesized by Fatty Acid Synthase 661 Fatty acids are synthesized and degraded by different pathways 661 The formation of malonyl CoA is the committed step in fatty acid synthesis 662 Intermediates in fatty acid synthesis are attached to an acyl carrier protein 662 Fatty acid synthesis consists of a series of condensation, reduction, dehydration, and reduction reactions 662 Fatty acids are synthesized by a multifunctional enzyme complex in animals 664 The synthesis of palmitate requires 8 molecules of acetyl CoA, 14 molecules of NADPH, and 7 molecules of ATP 666 Citrate carries acetyl groups from mitochondria to the cytoplasm for fatty acid synthesis 666 Several sources supply NADPH for fatty acid synthesis 667 Fatty acid metabolism is altered in tumor cells 667 22.5 The Elongation and Unsaturation of Fatty Acids are Accomplished by Accessory Enzyme Systems 668 Membrane-bound enzymes generate unsaturated fatty acids 668 Eicosanoid hormones are derived from polyunsaturated fatty acids 669 Variations on a theme: Polyketide and nonribosomal peptide synthetases resemble fatty acid synthase 670 22.6 Acetyl CoA Carboxylase Plays a Key Role in Controlling Fatty Acid Metabolism 670 Acetyl CoA carboxylase is regulated by conditions in the cell 671 Acetyl CoA carboxylase is regulated by a variety of hormones 671 CHAPTER 23 Protein Turnover and Amino Acid Catabolism 681 23.1 Proteins are Degraded to Amino Acids 682 The digestion of dietary proteins begins in the stomach and is completed in the intestine 682 Cellular proteins are degraded at different rates 682 23.2 Protein Turnover Is Tightly Regulated 683 Ubiquitin tags proteins for destruction 683 The proteasome digests the ubiquitin-tagged proteins 685 The ubiquitin pathway and the proteasome have prokaryotic counterparts 686 Protein degradation can be used to regulate biological function 687 23.3 The First Step in Amino Acid Degradation Is the Removal of Nitrogen 687 Alpha-amino groups are converted into ammonium ions by the oxidative deamination of glutamate 687 Mechanism: Pyridoxal phosphate forms Schiff-base intermediates in aminotransferases 689 Aspartate aminotransferase is an archetypal pyridoxaldependent transaminase 690 Blood levels of aminotransferases serve a diagnostic function 691 Pyridoxal phosphate enzymes catalyze a wide array of reactions 691 Serine and threonine can be directly deaminated 692 Peripheral tissues transport nitrogen to the liver 692 23.4 Ammonium Ion Is Converted into Urea in Most Terrestrial Vertebrates 693 The urea cycle begins with the formation of carbamoyl phosphate 693 Carbamoyl phosphate synthetase is the key regulatory enzyme for urea synthesis 694 Carbamoyl phosphate reacts with ornithine to begin the urea cycle 694 The urea cycle is linked to gluconeogenesis 696 Urea-cycle enzymes are evolutionarily related to enzymes in other metabolic pathways 696 Inherited defects of the urea cycle cause hyperammonemia and can lead to brain damage 697 Urea is not the only means of disposing of excess nitrogen 698 23.5 Carbon Atoms of Degraded Amino Acids Emerge as Major Metabolic Intermediates 698 Pyruvate is an entry point into metabolism for a number of amino acids 699 Oxaloacetate is an entry point into metabolism for aspartate and asparagine 700 Alpha-ketoglutarate is an entry point into metabolism for five-carbon amino acids 700 Succinyl coenzyme A is a point of entry for several nonpolar amino acids 701 Methionine degradation requires the formation of a key methyl donor, S-adenosylmethionine 701 The branched-chain amino acids yield acetyl CoA, acetoacetate, or propionyl CoA 701 Oxygenases are required for the degradation of aromatic amino acids 703 23.6 Inborn Errors of Metabolism Can Disrupt Amino Acid Degradation 705 Phenylketonuria is one of the most common metabolic disorders 706 Determining the basis of the neurological symptoms of phenylketonuria is an active area of research 706 CHAPTER 23 Protein Turnover and Amino Acid Catabolism 681

Contents xxvii Part III SYNTHESIZING THE MOLECULES OF LIFE CHAPTER 24 The Biosynthesis of Amino Acids 713 Amino acid synthesis requires solutions to three key biochemical problems 714 24.1 Nitrogen Fixation: Microorganisms Use ATP and a Powerful Reductant to Reduce Atmospheric Nitrogen to Ammonia 714 The iron–molybdenum cofactor of nitrogenase binds and reduces atmospheric nitrogen 715 Ammonium ion is assimilated into an amino acid through glutamate and glutamine 717 24.2 Amino Acids Are Made from Intermediates of the Citric Acid Cycle and Other Major Pathways 719 Human beings can synthesize some amino acids but must obtain others from their diet 719 Aspartate, alanine, and glutamate are formed by the addition of an amino group to an alpha-ketoacid 720 A common step determines the chirality of all amino acids 721 The formation of asparagine from aspartate requires an adenylated intermediate 721 Glutamate is the precursor of glutamine, proline, and arginine 722 3-Phosphoglycerate is the precursor of serine, cysteine, and glycine 722 Tetrahydrofolate carries activated one-carbon units at several oxidation levels 723 S-Adenosylmethionine is the major donor of methyl groups 724 Cysteine is synthesized from serine and homocysteine 726 High homocysteine levels correlate with vascular disease 726 Shikimate and chorismate are intermediates in the biosynthesis of aromatic amino acids 727 Tryptophan synthase illustrates substrate channeling in enzymatic catalysis 729 24.3 Feedback Inhibition Regulates Amino Acid Biosynthesis 730 Branched pathways require sophisticated regulation 731 The sensitivity of glutamine synthetase to allosteric regulation is altered by covalent modification 732 24.4 Amino Acids Are Precursors of Many Biomolecules 734 Glutathione, a gamma-glutamyl peptide, serves as a sulfhydryl buffer and an antioxidant 734 Nitric oxide, a short-lived signal molecule, is formed from arginine 735 Porphyrins are synthesized from glycine and succinyl coenzyme A 736 Porphyrins accumulate in some inherited disorders of porphyrin metabolism 737 CHAPTER 25 Nucleotide Biosynthesis 743 Nucleotides can be synthesized by de novo or salvage pathways 744 25.1 The Pyrimidine Ring Is Assembled de Novo or Recovered by Salvage Pathways 744 Bicarbonate and other oxygenated carbon compounds are activated by phosphorylation 745 The side chain of glutamine can be hydrolyzed to generate ammonia 745 Intermediates can move between active sites by channeling 745 Orotate acquires a ribose ring from PRPP to form a pyrimidine nucleotide and is converted into uridylate 746 Nucleotide mono-, di-, and triphosphates are interconvertible 747 CTP is formed by amination of UTP 747 Salvage pathways recycle pyrimidine bases 748 25.2 Purine Bases Can Be Synthesized de Novo or Recycled by Salvage Pathways 748 The purine ring system is assembled on ribose phosphate 749 The purine ring is assembled by successive steps of activation by phosphorylation followed by displacement 749 AMP and GMP are formed from IMP 751 Enzymes of the purine synthesis pathway associate with one another in vivo 752 Salvage pathways economize intracellular energy expenditure 752 25.3 Deoxyribonucleotides Are Synthesized by the Reduction of Ribonucleotides Through a Radical Mechanism 753 Mechanism: A tyrosyl radical is critical to the action of ribonucleotide reductase 753 Stable radicals other than tyrosyl radical are employed by other ribonucleotide reductases 755 Thymidylate is formed by the methylation of deoxyuridylate 755 Dihydrofolate reductase catalyzes the regeneration of tetrahydrofolate, a one-carbon carrier 756 Several valuable anticancer drugs block the synthesis of thymidylate 757 25.4 Key Steps in Nucleotide Biosynthesis Are Regulated by Feedback Inhibition 758 Pyrimidine biosynthesis is regulated by aspartate transcarbamoylase 758 The synthesis of purine nucleotides is controlled by feedback inhibition at several sites 758 The synthesis of deoxyribonucleotides is controlled by the regulation of ribonucleotide reductase 759 25.5 Disruptions in Nucleotide Metabolism Can Cause Pathological Conditions 760 The loss of adenosine deaminase activity results in severe combined immunodeficiency 760 Gout is induced by high serum levels of urate 761 Lesch–Nyhan syndrome is a dramatic consequence of mutations in a salvage-pathway enzyme 761 Folic acid deficiency promotes birth defects such as spina bifida 762 CHAPTER 24 The Biosynthesis of Amino Acids 713 CHAPTER 25 Nucleotide Biosynthesis 743