Harpers Illustrated Biochemistry 30th Edition
Understand the importance of the ability of cell-free extracts of yeast to ferment sugars, an observation that enabled discovery of the intermediates of fermentation, glycolysis, and other metabolic pathways.
■ Appreciate the scope of biochemistry and its central role in the life sciences, and that biochemistry and medicine are intimately related disciplines.
■ Appreciate that biochemistry integrates knowledge of the chemical processes in living cells with strategies to maintain health, understand disease, identify potential therapies, and enhance our understanding of the origins of life on earth.
■ Describe how genetic approaches have been critical for elucidating many areas of biochemistry, and how the Human Genome Project has furthered advances in numerous aspects of biology and medicine.
Biochemistry and medicine enjoy a mutually cooperative relationship. Biochemical studies have illuminated many aspects of health and disease, and the study of various aspects of health and disease has opened up new areas of biochemistry. The medical relevance of biochemistry both in normal and abnormal situations is emphasized throughout this book. Biochemistry makes significant contributions to the fields of cell biology, physiology, immunology, microbiology, pharmacology, and toxicology, as well as the fields of inflammation, cell injury, and cancer. These close relationships emphasize that life, as we know it, depends on biochemical reactions and processes.
The knowledge that yeast can convert the sugars to ethyl alcohol predates recorded history. It was not, however, until the earliest years of the 20th century that this process led directly to the science of biochemistry. Despite his insightful investigations of brewing and wine making, the great French microbiologist Louis Pasteur maintained that the process of fermentation could only occur in intact cells. His error was shown in 1899 by the brothers Büchner, who discovered that fermentation can indeed occur in cell-free extracts. This revelation resulted from storage of a yeast extract in a crock of concentrated sugar solution added as a preservative. Overnight, the contents of the crock fermented, spilled over the laboratory bench and floor, and dramatically demonstrated that fermentation can proceed in the absence of an intact cell.
This discovery made possible a rapid and highly productive series of investigations in the early years of the 20th century that initiated the science of biochemistry. These investigations revealed the vital role of inorganic phosphate, ADP, ATP, and NAD(H), and ultimately identified the phosphorylated sugars and the chemical reactions and enzymes (Gk “in yeast”) that convert glucose to pyruvate (glycolysis) or to ethanol and CO2 (fermentation). Subsequent research in the 1930s and 1940s identified the intermediates of the citric acid cycle and of urea biosynthesis, and provided insight into the essential roles of certain vitamin-derived cofactors or “coenzymes” such as thiamin pyrophosphate, riboflavin, and ultimately coenzyme A, coenzyme Q, and cobamide coenzymes. The 1950s revealed how complex carbohydrates are synthesized from, and broken down to simple sugars, and delineated the pathways for biosynthesis of pentoses and the breakdown of amino acids and lipids.
Animal models, perfused intact organs, tissue slices, cell homogenates and their subfractions, and purified enzymes all were used to isolate and identify metabolites and enzymes. These advances were made possible by the development in the late 1930s and early 1940s of techniques such as analytical ultracentrifugation, paper and other forms of chromatography, and the post-World War II availability of radioisotopes, principally 14C, 3H and 32P, as “tracers” to identify the intermediates in complex pathways such as that leading to the biosynthesis of cholesterol and other isoprenoids and the pathways of amino acid biosynthesis and catabolism. X-ray crystallography was then used to solve the three-dimensional structure, first of myoglobin, and subsequently of numerous proteins, polynucleotides, enzymes, and viruses including that of the common cold. Genetic advances that followed the realization that DNA was a double helix include the polymerase chain reaction, and transgenic animals or those with gene knockouts. The methods used to prepare, analyze, purify, and identify metabolites and the activities of natural and recombinant enzymes and their threedimensional structures are discussed in the following chapters.
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