Fundamentals of Biochemistry: Life at the Molecular Level

Citation

Voet, D., Voet, J. G., & Pratt, C. W. (2016). Fundamentals of Biochemistry: Life at the Molecular Level (5th ed.). John Wiley & Sons.

Chapter Summary

The book has 28 chapters in five parts and runs to about 1,180 pages. Chapter sections are numbered, and their lettered subsections are phrased as complete statements ("Next-Generation Sequencing Technologies Are Massively Parallel"), so the table of contents doubles as an outline of the argument. Many chapters carry boxed essays in three recurring series: Pathways of Discovery, Perspectives in Biochemistry and Biochemistry in Health and Disease.

Part I: Chapters 1–2: Introduction to the Chemistry of Life; Water

Chapter 1 covers the origin of life, cellular architecture (prokaryotes, eukaryotes and the three domains) and the thermodynamics needed for the rest of the book: the first and second laws, free energy and homeostasis. Chapter 2 treats the physical properties of water (polarity, the hydrophobic effect, osmosis and diffusion) and its chemical properties (ionization, pH and buffers).

Part II: Chapters 3–10: Biomolecules

• 3. Nucleotides, Nucleic Acids, and Genetic Information. Nucleotides, DNA and RNA structure, the function of nucleic acids, sequencing (from chain-terminator to next-generation methods) and the manipulation of DNA by cloning, libraries and PCR.
• 4. Amino Acids. Structure, stereochemistry and derivatives.
• 5. Proteins: Primary Structure. Polypeptide diversity, purification and analysis, protein sequencing (Edman degradation and mass spectrometry) and protein evolution.
• 6. Proteins: Three-Dimensional Structure. Secondary, tertiary and quaternary structure, structure determination by X-ray crystallography, NMR and cryo-electron microscopy, structural bioinformatics, stability, and folding, including chaperones and misfolding diseases.
• 7. Protein Function: Myoglobin and Hemoglobin, Muscle Contraction, and Antibodies. Three examples of how structure produces function: oxygen-binding proteins, muscle and antibodies.
• 8. Carbohydrates. Monosaccharides, polysaccharides and glycoproteins.
• 9. Lipids and Biological Membranes. Lipid classification, bilayers, membrane proteins, and membrane structure and assembly, including the secretory pathway and vesicle fusion.
• 10. Membrane Transport. The thermodynamics of transport, passive-mediated transport (ionophores, porins, channels, aquaporins) and active transport (ATPases and ABC transporters).

Part III: Chapters 11–13: Enzymes

Chapter 11, Enzymatic Catalysis, sets out the general properties of enzymes, activation energy and the main catalytic mechanisms, then applies them in two extended examples, lysozyme and the serine proteases. Chapter 12, Enzyme Kinetics, Inhibition, and Control, covers Michaelis–Menten and bisubstrate kinetics, competitive, uncompetitive and mixed inhibition, allosteric and covalent control, and a closing section on drug design. Chapter 13, Biochemical Signaling, moves from hormones through receptor tyrosine kinases and heterotrimeric G proteins to the phosphoinositide pathway.

Part IV: Chapters 14–22: Metabolism

Chapter 14 (Introduction to Metabolism) introduces pathways, "high-energy" compounds, oxidation–reduction reactions and experimental approaches, including labeled metabolites and systems biology. Chapters 15–19 follow carbohydrate and energy metabolism: Glucose Catabolism; Glycogen Metabolism and Gluconeogenesis; Citric Acid Cycle; Electron Transport and Oxidative Phosphorylation; and Photosynthesis (light reactions, the Calvin cycle and photorespiration). Chapters 20–22 turn to Lipid Metabolism and Amino Acid Metabolism, which both cover breakdown and biosynthesis, and Mammalian Fuel Metabolism: Integration and Regulation, which covers organ specialization, hormonal control, the regulation of energy metabolism and appetite, and disturbances in fuel metabolism.

Part V: Chapters 23–28: Gene Expression and Replication

Nucleotide Metabolism (23) and Nucleic Acid Structure (24) lead into DNA Replication, Repair, and Recombination (25), Transcription and RNA Processing (26), Protein Synthesis (27) and Regulation of Gene Expression (28), which ends with the cell cycle, cancer, apoptosis and development.

Key Concepts

Chapters 1–10: Foundations and biomolecules

• Free energy: the thermodynamic quantity that decides whether a process is spontaneous (Chapter 1).
• Hydrophobic effect: the tendency of nonpolar substances to aggregate in water, a theme in Chapters 2 and 9.
• Protein folding: the pathways, chaperone assistance and misfolding diseases of Chapter 6.
• Cooperativity: the cooperative binding of oxygen by hemoglobin (Chapter 7).
• Fluid mosaic model: the account of membrane structure in Chapter 9.

Chapters 11–13: Enzymes and signaling

• Catalytic mechanisms: acid–base, covalent, metal-ion and proximity catalysis, and binding of the transition state.
• Michaelis–Menten equation: the standard description of enzyme kinetics in Chapter 12.
• Allosteric control and covalent modification: the two classes of enzyme regulation.
• Second messengers: cAMP, IP3, Ca2+ and DAG in the pathways of Chapter 13.

Chapters 14–22: Metabolism

• Coupled reactions: how "high-energy" compounds such as ATP drive endergonic processes.
• Glycolysis, gluconeogenesis and the citric acid cycle: the central pathways, each presented with its regulation.
• Oxidative phosphorylation: electron transport complexes and ATP synthase driven by the flow of protons.
• Metabolic homeostasis: the regulation of energy metabolism, appetite and body weight in Chapter 22.

Chapters 23–28: Genetic information

• DNA replication, repair and recombination: the mechanisms covered in Chapter 25.
• Genetic code and translation: transfer RNA, ribosomes and posttranslational processing in Chapter 27.
• Regulation of gene expression: prokaryotic and eukaryotic control in Chapter 28.

Critical Analysis

Strengths

• Explicit chemical grounding. The publisher describes the edition as a biochemical foundation "rooted in chemistry", and the headings bear this out: thermodynamics appears in Chapter 1 and again in Chapter 14, and Chapters 11 and 12 work through enzyme mechanisms and kinetics rather than listing enzyme properties.
• Current methods. The table of contents includes next-generation sequencing, mass spectrometry, cryo-electron microscopy, structural bioinformatics and systems biology, and the publisher highlights structural biology and bioinformatics as the edition's focus.
• Human context. The Biochemistry in Health and Disease boxes (for example on lactose intolerance, glycogen storage diseases and telomerase) and the Pathways of Discovery biographies (Franklin, Sanger, Perutz, Banting and Best, among others) give context to the pathways.
• Study apparatus. The publisher's Chapter 1 excerpt shows Key Concepts at the start of each numbered section, sample calculations with companion videos, a Key Terms list with page references, end-of-chapter problems, short online bioinformatics exercises and annotated references.

Limitations

• Length. With 28 chapters and about 1,180 pages, the book contains more than a single semester can cover; instructors and self-learners must choose chapters.
• Chemistry prerequisites. Free energy, pK values, the Nernst equation and reaction mechanisms appear from the early chapters, so the book is harder going for readers whose chemistry is thin.
• Solutions access. Solutions to odd-numbered problems are listed on the Wiley companion site rather than in the book, so work on the other problems needs a study partner or an instructor.
• Weight of metabolism and gene expression. Parts IV and V run from page 442 to the end of the text, which is more than half of the book, so a course that gives equal time to structure and enzymes has to cut.

Where It Fits in the Course

This is a full-length biochemistry text built on chemical principles. Essential Biochemistry (Pratt and Cornely) is described as a concise text for a one-semester first course, and McKee's Biochemistry: The Molecular Basis of Life as an introduction for students with limited chemistry, so either can come before Voet. Miesfeld and McEvoy's Biochemistry ties molecular structure and metabolism to physiology, nutrition and disease and is an alternative with a physiological emphasis.

Lehninger Principles of Biochemistry is described as giving comprehensive coverage of biological molecules, metabolic pathways and cellular processes, so it is the closest alternative as a main text. Kuriyan, Konforti and Wemmer's The Molecules of Life approaches biomolecules through thermodynamics, statistical mechanics and kinetics and suits readers who want that physical depth after a text like this one. From the chemistry shelf, McMurry and Begley's The Organic Chemistry of Biological Pathways is a companion for the reaction mechanisms behind Chapters 14–23.

How to Use This Book

The book is aimed at students in a full-year or demanding one-semester biochemistry course who have completed general and organic chemistry and introductory biology. A practical plan:

• Core: Chapters 3–9 (biomolecules), 11–12 (enzymes), 14–18 (metabolic principles, glycolysis, the citric acid cycle and oxidative phosphorylation) and 25–27 (replication, transcription, translation).
• Selective: Chapters 10, 13, 19, 20–23 and 28 can be assigned according to the course; courses with a separate molecular biology class may skim Chapters 24–28.
• Review: Chapters 1–2 are worth reading even if the material is familiar, since the thermodynamic vocabulary is used throughout.

Read each section's Key Concepts first, work the sample calculations before the problems, and use the Key Terms lists for revision. For Chapter 6, pair the section on structural bioinformatics with the online bioinformatics exercises. The boxed essays are optional but worth sampling, especially where they connect a pathway to a disease.