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_Notes_Chapters.txt
18/01/2005
Sample Chapters and Art for Lehninger Principles of Biochemistry, Fourth
Edition
The classic introduction to biochemistry.
**********Sample Chapters: Note: The sample chapters here are uncorrected
page proofs. Chapters are being reviewed a final time before
publication.***********
PART I. STRUCTURE AND CATALYSIS
Chapter 1: The Foundations of Biochemistry
Distilled and reorganized from Chapters 1 to 3 of the previous edition,
this overview provides a refresher on the cellular, chemical, physical,
genetic, and evolutionary background to biochemistry, while orienting
students toward what is unique about biochemistry.
Chapter 2: Water
Includes new coverage of the concept of protein-bound water, illustrated
with molecular graphics.
Chapter 3: Amino Acids, Peptides, and Proteins
Adds important new material on genomics and proteomics and their
implications for the study of protein structure, function, and evolution.
Chapter 4: The Three-Dimensional Structure of Proteins
Adds a new box on scurvy.
Chapter 5: Protein Function
Adds a new box on carbon monoxide poisoning.
Chapter 6: Enzymes
Offers a revised presentation of the mechanism of chymotrypsin (the first
reaction mechanism in the book), featuring a two-page figure that takes
students through this particular mechanism, while serving as a step-by-step
guide to interpreting any reaction mechanism. Features new coverage of the
mechanism for lysozyme including the controversial aspects of the mechanism
and currently favored resolution based on work published in 2001.
Chapter 7: Carbohydrates and Glycobiology
Includes new section on polysaccharide conformations. A striking new
discussion of the "sugar code" looks at polysaccharides as informational
molecules, with detailed discussions of lectins, selectins, and
oligosaccharide-bearing hormones. Features new material on structural
heteropolysaccharides and proteoglycans. Covers recent techniques for
carbohydrate analysis.
Chapter 8: Nucleotides and Nucleic Acids
Chapter 9: DNA-Based Information Technologies
Introduces the human genome. Biochemical insights derived from the human
genome are integrated throughout the text. Tracking the emergence of
genomics and proteomics, this chapter establishes DNA technology as a core
topic and a path to understanding metabolism, signaling, and other topics
covered in the middle chapters of this edition. Includes up-to-date
coverage of microarrays, protein chips, comparative genomics, and
techniques in cloning and analysis.
Chapter 10: Lipids
Integrates new topics specific to chloroplasts and archaebacteria. Adds
material on lipids as signal molecules.
Chapter 11: Biological Membranes and Transport
Includes a description of membrane rafts and microdomains within membranes,
and a new box on the use of atomic force microscopy to visualize them.
Looks at the role of caveolins in the formation of membrane caveolae.
Covers the investigation of hop diffusion of membrane lipids using FRAP
(fluorescence recovery after photobleaching). Adds new details to the
discussion of the mechanism of Ca2- ATPase (SERCA pump), revealed by the
recently available high-resolution view of its structure. Explores new
facets of the mechanisms of the K+ selectivity filter, brought to light by
recent high-resolution structures of the K+ channel. Illuminates the
structure, role, and mechanism of aquaporins with important new details.
Describes ABC transporters, with particular attention to the multidrug
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transporter (MDR1). Includes the newly solved structure of the lactose
transporter of E. coli.
Chapter 12: Biosignaling
Updates the previous edition's groundbreaking chapter to chart the
continuing rapid development of signaling research. Includes discussion on
general mechanisms for activation of protein kinases in cascades. Now
covers the roles of membrane rafts and caveolae in signaling pathways,
including the activities of AKAPs (A Kinase Anchoring Proteins) and other
scaffold proteins. Examines the nature and conservation of families of
multivalent protein binding modules, which combine to create many discrete
signaling pathways. Adds a new discussion of signaling in plants and
bacteria, with comparison to mammalian signaling pathways. Features a new
box on visualizing biochemistry with fluorescence resonance energy transfer
(FRET) with green fluorescent protein (GFP).
PART II: BIOENERGETICS AND METABOLISM
Chapter 13: Principles of Bioenergetics
Chapter 14: Glycolysis, Gluconeogenesis, and the Pentose Phosphate Pathway
Now covers gluconeogenesis immediately after glycolysis, discussing their
relatedness, differences, and coordination and setting up the completely
new chapter on metabolic regulation that follows. Adds coverage of the
mechanisms of phosphohexose isomerase and aldolase. Revises the
presentation of the mechanism of glyceraldehyde 3-phosphate dehydrogenase.
New Chapter!
Chapter 15: Principles of Metabolic Regulation, Illustrated with Glucose
and Glycogen Metabolism
Brings together the concepts and principles of metabolic regulation in one
chapter. Concludes with the latest conceptual approaches to the regulation
of metabolism, including metabolic control analysis and contemporary
methods for studying and predicting the flux through metabolic pathways.
Chapter 16: The Citric Acid Cycle
Expands and updates the presentation of the mechanism for pyruvate
carboxylase. Adds coverage of the mechanisms of isocitrate dehydrogenase
and citrate synthase.
Chapter 17: Fatty Acid Catabolism
Updates coverage of trifunctional protein. New section on the role of
perilipin phosphorylation in the control of fat mobilization. New
discussion of the role of acetyl-CoA in the integration of fatty acid
oxidation and synthesis. Updates coverage of the medical consequences of
genetic defects in fatty acyl CoA dehydrogenases. Takes a fresh look at
medical issues related to peroxisomes.
Chapter 18: Amino Acid Oxidation and the Production of Urea
Integrates the latest on regulation of reactions throughout the chapter,
with new material on genetic defects in urea cycle enzymes, and updated
information on the regulatory function of N-acetylglutamate synthase.
Reorganizes coverage of amino acid degradation to focus on the big picture.
Adds new material on the relative importance of several degradative
pathways. Includes a new description of the interplay of the pyridoxal
phosphate and tetrahydrofolate cofactors in serine and glycine metabolism.
Chapter 19: Oxidative Phosphorylation and Photophosphorylation
Adds a prominent new section on the roles of mitochondria in apoptosis and
oxidative stress. Now covers the role of IF1 in the inhibition of ATP
synthase during ischemia. Includes revelatory details on the light-
dependent pathways of electron transfer in photosynthesis, based on newly
available molecular structures.
Chapter 20: Carbohydrate Biosynthesis in Plants and Bacteria
Reorganizes the coverage of photosynthesis and the C4 and CAM pathways.
Adds a major new section on the synthesis of cellulose and bacterial
peptidoglycan.
Chapter 21: Lipid Biosynthesis
Features an important new section on glyceroneogenesis and the
triacylglycerol cycle between adipose tissue and liver, including their
roles in fatty acid metabolism (especially during starvation) and the
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emergence of thiazolidinediones as regulators of glyceroneogenesis in the
treatment of type II diabetes. Includes a timely new discussion on the
regulation of cholesterol metabolism at the genetic level, with
consideration of sterol regulatory element-binding proteins (SREBPs).
Chapter 22: Biosynthesis of Amino Acids, Nucleotides, and Related Molecules
Adds material on the regulation of nitrogen metabolism at the level of
transcription. Significantly expands coverage of synthesis and degradation
of heme.
Chapter 23: Integration and Hormonal Regulation of Mammalian Metabolism
Reorganized presentation leads students through the complex interactions of
integrated metabolism step by step. Features extensively revised coverage
of insulin and glucagon metabolism that includes the integration of
carbohydrate and fat metabolism. New discussion of the role of AMP-
dependent protein kinase in metabolic integration. Updates coverage of the
fast-moving field of obesity, regulation of body mass, and the leptin and
adiponectin regulatory systems. Adds a discussion of Ghrelin and PYY3-36 as
regulators of short-term eating behavior. Covers the effects of diet on the
regulation of gene expression, considering the role of peroxisome
proliferator-activated receptors (PPARs)
PART III. INFORMATION PATHWAYS
Chapter 24: Genes and Chromosomes
Integrates important new material on the structure of chromosomes,
including the roles of SMC proteins and cohesins, the features of
chromosomal DNA, and the organization of genes in DNA.
Chapter 25: DNA Metabolism
Adds a section on the "replication factories" of bacterial DNA. Includes
latest perspectives on DNA recombination and repair.
Chapter 26: RNA Metabolism
Updates coverage on mechanisms of mRNA processing. Adds a subsection on the
5' cap of eukaryotic mRNAs. Adds important new information about the
structure of bacterial RNA polymerase and its mechanism of action.
Chapter 27: Protein Metabolism
Includes a presentation and analysis of the long-awaited structure of the
ribosome--one of the most important updates in this new edition. Adds a new
box on the evolutionary significance of ribozyme-catalyzed peptide
synthesis.
Chapter 28: Regulation of Gene Expression
Adds a new section on RNA interference (RNAi), including the medical
potential of gene silencing.
3
1
THE FOUNDATIONS
OF BIOCHEMISTRY
1.1 Cellular Foundations
3
1.2 Chemical Foundations
12
1.3 Physical Foundations
21
1.4 Genetic Foundations
28
1.5 Evolutionary Foundations
31
life arose—simple microorganisms with the ability to ex-
tract energy from organic compounds or from sunlight,
which they used to make a vast array of more complex
biomolecules
from the simple elements and compounds
on the Earth’s surface.
Biochemistry asks how the remarkable properties
of living organisms arise from the thousands of differ-
ent lifeless biomolecules. When these molecules are iso-
lated and examined individually, they conform to all the
physical and chemical laws that describe the behavior
of inanimate matter—as do all the processes occurring
in living organisms. The study of biochemistry shows
how the collections of inanimate molecules that consti-
tute living organisms interact to maintain and perpetu-
ate life animated solely by the physical and chemical
laws that govern the nonliving universe.
Yet organisms possess extraordinary attributes,
properties that distinguish them from other collections
of matter. What are these distinguishing features of liv-
ing organisms?
With the cell, biology discovered its atom ...To
characterize life, it was henceforth essential to study the
cell and analyze its structure: to single out the common
denominators, necessary for the life of every cell;
alternatively, to identify differences associated with the
performance of special functions.
—François Jacob,
La logique du vivant: une histoire de l’hérédité
(The Logic of Life: A History of Heredity),
1970
We must, however, acknowledge, as it seems to me, that
man with all his noble qualities . . . still bears in his
bodily frame the indelible stamp of his lowly origin.
—Charles Darwin,
The Descent of Man,
1871
A high degree of chemical complexity and
microscopic organization.
Thousands of differ-
ent molecules make up a cell’s intricate internal
structures (Fig. 1–1a). Each has its characteristic
sequence of subunits, its unique three-dimensional
structure, and its highly specific selection of
binding partners in the cell.
Systems for extracting, transforming, and
using energy from the environment
(Fig.
1–1b), enabling organisms to build and maintain
their intricate structures and to do mechanical,
chemical, osmotic, and electrical work. Inanimate
matter tends, rather, to decay toward a more
disordered state, to come to equilibrium with its
surroundings.
as a cataclysmic eruption of hot, energy-rich sub-
atomic particles. Within seconds, the simplest elements
(hydrogen and helium) were formed. As the universe
expanded and cooled, material condensed under the in-
fluence of gravity to form stars. Some stars became
enormous and then exploded as supernovae, releasing
the energy needed to fuse simpler atomic nuclei into the
more complex elements. Thus were produced, over bil-
lions of years, the Earth itself and the chemical elements
found on the Earth today. About four billion years ago,
1
chapter
F
ifteen to twenty billion years ago, the universe arose
2
Chapter 1 The Foundations of Biochemistry
(a)
This is true not only of macroscopic structures,
such as leaves and stems or hearts and lungs, but
also of microscopic intracellular structures and indi-
vidual chemical compounds. The interplay among
the chemical components of a living organism is dy-
namic; changes in one component cause coordinat-
ing or compensating changes in another, with the
whole ensemble displaying a character beyond that
of its individual parts. The collection of molecules
carries out a program, the end result of which is
reproduction of the program and self-perpetuation
of that collection of molecules—in short, life.
A history of evolutionary change.
Organisms
change their inherited life strategies 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.
(b)
Despite these common properties, and the funda-
mental unity of life they reveal, very few generalizations
about living organisms are absolutely correct for every
organism under every condition; there is enormous di-
versity. The range of habitats in which organisms live,
from hot springs to Arctic tundra, from animal intestines
to college dormitories, is matched by a correspondingly
wide range of specific biochemical adaptations, achieved
(c)
FIGURE 1–1
Some characteristics of living matter. (a)
Microscopic
complexity and organization are apparent in this colorized thin sec-
tion of vertebrate muscle tissue, viewed with the electron microscope.
(b)
A prairie falcon acquires nutrients by consuming a smaller bird.
(c)
Biological reproduction occurs with near-perfect fidelity.
A capacity for precise self-replication and
self-assembly
(Fig. 1–1c). A single bacterial cell
placed in a sterile nutrient medium can give rise
to 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
within the genetic material of the original cell.
Mechanisms for sensing and responding to
alterations in their surroundings,
constantly
adjusting to these changes by adapting their
internal chemistry.
Defined functions for each of their compo-
nents and regulated interactions among them.
FIGURE 1–2
Diverse living organisms share common chemical fea-
tures.
Birds, beasts, plants, and soil microorganisms share with hu-
mans the same basic structural units (cells) and the same kinds of
macromolecules (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 “The Garden of Eden,” by Jan van Kessel the Younger
(1626–1679).
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