The Chemical Educator, Vol. 6, No. 1, S1430-4171(01)01455-4, 10.1007/s00897000455a © 2001 Springer-Verlag New York, Inc.

Lehninger Principles of Biochemistry, 3rd edition; By David L. Nelson and Michael M. Cox. Worth Publishers: New York, 2000. ISBN 1-57259-9316. 1255 pp. $116.45.


Reveiwed by, Matthew Fisher, St Vincent College,


For decades, Albert Lehninger’s biochemistry textbooks were universally recognized as classics in the field. In 1982, Lehninger authored Principles of Biochemistry, a complete revision and reorganization of his earlier Biochemistry. Upon Lehninger’s death in the late 1980s, the responsibility of authorship fell to David Nelson and Michael Cox, both of the University of Wisconsin. Their efforts resulted in a second edition of Principles of Biochemistry in 1993 and a brand new third edition published this year.


The third edition of what is now titled Lehninger Principles of Biochemistry largely follows the same format as earlier editions. The first section, “Foundations of Biochemistry” provides an overview of broad themes in biochemistry and includes several chapters that review material students have presumably seen in earlier courses—cell structure and function, chemical bonding and three-dimensional structure, chemical reactivity, and the chemistry of water and aqueous solutions. The second section, “Structure and Catalysis,” starts with the structures of amino acids and proteins, then goes on to cover protein function, enzymes, carbohydrates, nucleotides, nucleic acids, lipids, biological membranes, transport, and signal transduction. “Bioenergetics and Metabolism” is the focus of the third section, and here can be found all the major catabolic and anabolic pathways that are traditionally covered in upper-level biochemistry courses. Finally, the fourth section covers “Information Pathways” such as DNA replication, RNA metabolism, protein synthesis and degradation, as well as an overview of genes, chromosomes, and recombinant DNA technology.


Principles of Biochemistry has always, in my opinion, taken a perspective that is slightly different than other biochemistry textbooks, a perspective that places more emphasis on balancing biological and chemical concepts. A quick glance at similar textbooks in my office showed that only Nelson and Cox include an entire chapter that reviews cell structure and function. While many other biochemistry textbooks place a chapter that reviews thermodynamics early in the text, Principles of Biochemistry instead includes a chapter that reviews important concepts from organic chemistry such as chemical bonding, chemical reactivity, and three-dimensional structure. While thermodynamics is mentioned throughout the first two sections, it is only at the beginning of the section on bioenergetics that a review of concepts such as the First and Second Laws and chemical potential can be found.


Nelson and Cox include topics such as cell-cycle control by protein kinases and apoptosis in this text; these are topics that I see as being closer to what some instructors would cover in a molecular cell biology course. At the same time, the text does not come across as presenting some chemical concepts with the same rigor as some other textbooks. Consequently, I think it would be more understandable for a wider range of students, including those more interested in the biological aspects of biochemistry. None of my comments should be taken as criticisms of Principles of Biochemistry; my point is simply that it takes a particular approach that will be very appropriate for some courses and less so for others.


Several revisions in this edition serve to improve the textbook significantly. What were two separate chapters on amino acids and an overview of proteins/peptides have been combined into a single chapter that reads much more smoothly and succinctly. Boxed supplementary information was a feature of the earlier edition, but the number of boxes has been greatly expanded, from 36 to 52, in the new edition. In addition to expanding the amount of supplementary information, Nelson and Cox have emphasized in these boxes the relevance of biochemistry to medicine, biotechnology, and other areas. More descriptions of experimental techniques have been incorporated. The chapter on carbohydrates has been significantly strengthened by the inclusion of new information on the role of glycoproteins in processes such as cell–cell recognition and adhesion.


Signal transduction now has a chapter to itself, rather than being grouped with hormonal control and integration of metabolism. The material in this chapter is generally quite good, covering several different classes of signal transduction mechanisms: gated ion channels, receptor tyrosine kinases, and G-protein–coupled receptors in both metabolic pathways and sensory pathways such as vision and olfaction.


I have always been impressed with the quality of the problems found at the end of each chapter; the authors have revised some problems for this new edition and added several problems that require students to use Internet resources such as the Protein Data Bank. And it should come as no surprise that the authors have incorporated more recent findings—such as three-dimensional structures of biochemically significant molecules like the potassium ion transporter and the mechanism of ATP synthase—throughout the text where appropriate.


At the same time, the new edition suffers from some of the same weaknesses that I found with its predecessor. I find the presentation of the MWC symmetry and KNF sequential models for allosteric regulation to be much weaker than other texts, in part because Nelson and Cox completely avoid any of the quantitative aspects of MWC theory. Unlike every other biochemistry textbook that I know of, Nelson and Cox continue to fragment their presentation of photosynthesis, with photophosphorylation covered in the same chapter as oxidative phosphorylation and the Calvin cycle reactions covered in a separate chapter with glycogen synthesis and gluconeogenesis. Several other textbooks cover regulation of gene expression in a separate chapter from the one where basic concepts of RNA synthesis and editing are presented. However, Principles of Biochemistry places the chapter on regulation several chapters after the section where RNA synthesis is described. In addition, the organization of the gene regulation chapter is weak, with a section on structural characteristics of domains in DNA binding proteins inserted in the middle of the section that covers how the lac operon works. The same chapter also appears to lack any structural information about TBP and current models for how it might interact with TBP associated factors.


As with many textbooks published today, Principles of Biochemistry is accompanied by a CD-ROM and a Website (Avail. URL: The CD is a special version designed to accompany this particular text of the Understand! Biochemistry software developed by the Mona Group. It consists of an index of terms, a number of minicourses, web links, and 30 quizzes organized by topics. I examined several minicourses—Proteins in Action: Allosteric Enzymes, Catalysis and Regulation; Citric Acid Cycle; and Signal Transduction. The quality of the minicourses varied; that for the Citric Acid Cycle added nothing to the material presented in the text, while the Signal Transduction minicourse did add more detail to concepts presented in the book.


I had mixed feelings about those covering Allosteric Enzymes and Catalysis and Regulation. Sometimes they gave a very nice perspective on the material and made excellent use of structural graphics; at other times I felt some material in these minicourses added nothing to a student’s learning experience or even served to make some concepts more confusing. The quizzes are generally well-designed and focus on important lower-level thinking skills such as defining, explaining, and relating. I was quite pleased to see that the quizzes were structured to provide commentary on student responses so that students who provided incorrect responses could be helped to see where they misunderstood the material. Each of the quizzes provided a student with the opportunity to review or retake a quiz and to have the software provide the correct answer. Overall, I felt that the CD was a nice supplement with some limited applications, and that it marginally enhanced the quality of the textbook.


The Website appears to be in the early stages of development, but there are links for 3‑D structural tutorials and links to Internet sites that can be used to answer some of the end-of-chapter problems. There are also links to sites where RasMol and MDL Chemscape Chime can be downloaded, a section under development that will provide suggestions for using Chime, and Microsoft PowerPoint slides for each chapter that can be downloaded. When I looked at this site at the end of June 2000, there were six 3-D structural tutorials available online. These tutorials utilize the Chime plug-in to guide students through material designed to enhance their understanding of the structural bases of many biochemical phenomena. While much of the Website appears to be under development at this point, I was quite pleased with what I saw and believe that the completed site will be a very useful resource for instructors.


Overall, the third edition of Lehninger Principles of Biochemistry has maintained many of the strengths found in earlier editions while incorporating some very nice improvements along with recent discoveries in biochemistry. This textbook would be an excellent choice for two-semester undergraduate courses, particularly those courses with a broad range of students who are likely to have varying backgrounds in biology and chemistry.