Saturday, May 7, 2011

STRUCTURE AND CATALYSIS

The science of biochemistry can be dated to Eduard Buchner’s pioneering discovery. His finding opened a world of chemistry that has inspired researchers for well over a century. Biochemistry is nothing less than the chemistry of life, and, yes, life can be investigated, analyzed, and understood. To begin, every student of biochemistry needs both a language and some fundamentals; these are provided in Part I.
The chapters of Part I are devoted to the structure and function of the major classes of cellular constituents:
water (Chapter 2), amino acids and proteins (Chapters 3 through 6), sugars and polysaccharides
(Chapter 7), nucleotides and nucleic acids (Chapter 8), fatty acids and lipids (Chapter 10), and, finally, membranes and membrane signaling proteins (Chapters 11 and 12). We supplement this discourse on molecules with information about the technologies used to study them. Some of the techniques sections are woven throughout the molecular descriptions, although one entire chapter (Chapter 9) is devoted to an integrated suite of modern advances in biotechnology that have greatly accelerated the pace of discovery.
The molecules found in a cell are a major part of the language of biochemistry; familiarity with them is a
prerequisite for understanding more advanced topics covered in this book and for appreciating the rapidly
growing and exciting literature of biochemistry. We begin with water because its properties affect the structure
and function of all other cellular constituents. For each class of organic molecules, we first consider the
covalent chemistry of the monomeric units (amino acids, monosaccharides, nucleotides, and fatty acids)
and then describe the structure of the macromolecules and supramolecular complexes derived from them. An
overriding theme is that the polymeric macromolecules in living systems, though large, are highly ordered chemical entities, with specific sequences of monomeric subunits giving rise to discrete structures and functions.
This fundamental theme can be broken down into three interrelated principles: (1) the unique structure of each
macromolecule determines its function; (2) noncovalent interactions play a critical role in the structure and thus
the function of macromolecules; and (3) the monomeric subunits in polymeric macromolecules occur in specific sequences, representing a form of information upon which the ordered living state depends.
The relationship between structure and function is especially evident in proteins, which exhibit an extraordinary
diversity of functions. One particular polymeric sequence of amino acids produces a strong, fibrous structure
found in hair and wool; another produces a protein that transports oxygen in the blood; a third binds other
proteins and catalyzes the cleavage of the bonds between their amino acids. Similarly, the special functions of polysaccharides, nucleic acids, and lipids can be understood as a direct manifestation of their chemical structure, with their characteristic monomeric subunits linked in precise functional polymers. Sugars linked together become energy stores, structural fibers, and points of specific molecular recognition; nucleotides strung together in DNA or RNA provide the blueprint for an entire organorganism; and aggregated lipids form membranes. Chapter 12 unifies the discussion of biomolecule function, describing how specific signaling systems regulate the activities of biomolecules—within a cell, within an organ, and among organs—to keep an organism in homeostasis.
As we move from monomeric units to larger and larger polymers, the chemical focus shifts from covalent
bonds to noncovalent interactions. The properties of covalent bonds, both in the monomeric subunits and in the bonds that connect them in polymers, place constraints on the shapes assumed by large molecules. It is the numerous noncovalent interactions, however, that dictate the stable native conformations of large molecules while permitting the flexibility necessary for their biological function. As we shall see, noncovalent interactions are essential to the catalytic power of enzymes, the critical interaction of complementary base pairs in nucleic
acids, the arrangement and properties of lipids in membranes, and the interaction of a hormone or growth factor with its membrane receptor.
The principle that sequences of monomeric subunits are rich in information emerges most fully in the discussion of nucleic acids (Chapter 8). However, proteins and some short polymers of sugars (oligosaccharides)
are also information-rich molecules. The amino acid sequence is a form of information that directs the
folding of the protein into its unique three-dimensional structure, and ultimately determines the function of the
protein. Some oligosaccharides also have unique sequences and three-dimensional structures that are recognized by other macromolecules.
Each class of molecules has a similar structural hierarchy: subunits of fixed structure are connected by bonds of limited flexibility to form macromolecules with three-dimensional structures determined by noncovalent interactions. These macromolecules then interact to form the supramolecular structures and organelles
that allow a cell to carry out its many metabolic functions.

Together, the molecules described in Part I are the stuff of life. We begin with water.
Principles of biochemistry-Lehninger page 45-46
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