8885dc06190-2371/27/047:13 AM Page191mac76mac76:385 6.1 An Introduction to Enzymes 191 not only in medicine but in the chemical industry, food structure and chemical mechanism of many of them, and processing, and agriculture a general understanding of how enzymes work. e begin with descriptions of the properties of en- zymes and the principles underlying their catalytic Most Enzymes Are Proteins power, then introduce enzyme kinetics, a discipline that provides much of the framework for any discussion of with the exception of a small group of catalytic rNa nzymes. Specific examples of enzyme mechanisms are molecules(Chapter 26), all enzymes are proteins. Their then provided, illustrating principles introduced earlier catalytic activity depends on the integrity of their na- tive protein conformation. If an enzyme is denatured ol in the chapter. We end with a discussion of how enzyme dissociated into its subunits, catalytic activity is usually activity is regulated lost. If an enzyme is broken down into its component amino acids, its catalytic activity is always destroyed 6.1 An Introduction to Enzymes Thus the primary, secondary, tertiary, and quaternary structures of protein enzymes are essential to their cat Much of the history of biochemistry is the history of en- alytic activity zyme research. Biological catalysis was first recognized Enzymes, like other proteins, have molecular and described in the late 1700s. in studies on the di- weights ranging from about 12,000 to more than I mil- gestion of meat by secretions of the stomach, and re- lion. Some enzymes require no chemical groups for search continued in the 1800s with examinations of the activity other than their amino acid residues. Others conversion of starch to sugar by saliva and various plant require an additional chemical component called a extracts In the 1850s. Louis pasteur concluded that fer- cofactor--either one or more inorganic ions, such as mentation of sugar into alcohol by yeast is catalyzed by Fe, Mg, Mn-t, or Zn (Table 6-1), or a complex ferments. He postulated that these ferments were in- organic or metalloorganic molecule called a coenzyme separable from the structure of living yeast cells; this (Table 6-2). Some enzymes require both a coenzyme view, called vitalism, prevailed for decades. Then in 1897 Eduard Buchner discovered that yeast extracts could ferment sugar to alcohol, proving that fermentation was TABLE 6-1 Some Inorganic Elements That promoted by molecules that continued to function when Serve as Cofactors for Enzymes removed from cells. Frederick W. Kuhne called these molecules enzymes. As vitalistic notions of life were Cytochrome oxidase disproved, the isolation of new enzymes and the inves Fe or Fe Cytochrome oxidase, catalase, peroxidase tigation of their properties advanced the science of Pyruvate kinase biochemistry. Hexokinase, glucose 6-phosphatase, The isolation and crystallization of urease by James Sumner in 1926 provided a breakthrough in early enzyme Arginase, ribonucleotide reductase studies. Sumner found that urease crystals consisted Dinitrogenase entirely of protein, and he postulated that all enzymes Urease are proteins. In the absence of other examples, this Se Glutathione peroxidase idea remained controversial for some time. Only in the Carbonic anhydrase, alcohol 1930s was Sumner's conclusion widely accepted, after dehydrogenase, carboxypeptidases John Northrop and Moses Kunitz crystallized pepsin, A and B trypsin, and other digestive enzymes and found them also to be proteins. During this period L.B. S. Haldane wrote a treatise entitled Enzymes. Although the molecular nature of enzymes was not yet fully appreciated Haldane made the remarkable suggestion that weak bonding interactions between an enzyme and its substrate might be used to catalyze a reaction. This insight lies at the heart of our current under- Since the latter part of the twentieth century, research on enzymes has been intensive. It has led to the purification of Eduard Buchner, James Sumner 1. B S. Haldane thousands of enzymes, elucidation of the 1860-1917 1887-1955 1892-1964not only in medicine but in the chemical industry, food processing, and agriculture. We begin with descriptions of the properties of en￾zymes and the principles underlying their catalytic power, then introduce enzyme kinetics, a discipline that provides much of the framework for any discussion of enzymes. Specific examples of enzyme mechanisms are then provided, illustrating principles introduced earlier in the chapter. We end with a discussion of how enzyme activity is regulated. 6.1 An Introduction to Enzymes Much of the history of biochemistry is the history of en￾zyme research. Biological catalysis was first recognized and described in the late 1700s, in studies on the di￾gestion of meat by secretions of the stomach, and re￾search continued in the 1800s with examinations of the conversion of starch to sugar by saliva and various plant extracts. In the 1850s, Louis Pasteur concluded that fer￾mentation of sugar into alcohol by yeast is catalyzed by “ferments.” He postulated that these ferments were in￾separable from the structure of living yeast cells; this view, called vitalism, prevailed for decades. Then in 1897 Eduard Buchner discovered that yeast extracts could ferment sugar to alcohol, proving that fermentation was promoted by molecules that continued to function when removed from cells. Frederick W. Kühne called these molecules enzymes. As vitalistic notions of life were disproved, the isolation of new enzymes and the inves￾tigation of their properties advanced the science of biochemistry. The isolation and crystallization of urease by James Sumner in 1926 provided a breakthrough in early enzyme studies. Sumner found that urease crystals consisted entirely of protein, and he postulated that all enzymes are proteins. In the absence of other examples, this idea remained controversial for some time. Only in the 1930s was Sumner’s conclusion widely accepted, after John Northrop and Moses Kunitz crystallized pepsin, trypsin, and other digestive enzymes and found them also to be proteins. During this period, J. B. S. Haldane wrote a treatise entitled Enzymes. Although the molecular nature of enzymes was not yet fully appreciated, Haldane made the remarkable suggestion that weak bonding interactions between an enzyme and its substrate might be used to catalyze a reaction. This insight lies at the heart of our current under￾standing of enzymatic catalysis. Since the latter part of the twentieth century, research on enzymes has been intensive. It has led to the purification of thousands of enzymes, elucidation of the structure and chemical mechanism of many of them, and a general understanding of how enzymes work. Most Enzymes Are Proteins With the exception of a small group of catalytic RNA molecules (Chapter 26), all enzymes are proteins. Their catalytic activity depends on the integrity of their na￾tive protein conformation. If an enzyme is denatured or dissociated into its subunits, catalytic activity is usually lost. If an enzyme is broken down into its component amino acids, its catalytic activity is always destroyed. Thus the primary, secondary, tertiary, and quaternary structures of protein enzymes are essential to their cat￾alytic activity. Enzymes, like other proteins, have molecular weights ranging from about 12,000 to more than 1 mil￾lion. Some enzymes require no chemical groups for activity other than their amino acid residues. Others require an additional chemical component called a cofactor—either one or more inorganic ions, such as Fe2
, Mg2
, Mn2
, or Zn2
(Table 6–1), or a complex organic or metalloorganic molecule called a coenzyme (Table 6–2). Some enzymes require both a coenzyme 6.1 An Introduction to Enzymes 191 Cu2
Cytochrome oxidase Fe2
or Fe3
Cytochrome oxidase, catalase, peroxidase K
Pyruvate kinase Mg2
Hexokinase, glucose 6-phosphatase, pyruvate kinase Mn2
Arginase, ribonucleotide reductase Mo Dinitrogenase Ni2
Urease Se Glutathione peroxidase Zn2
Carbonic anhydrase, alcohol dehydrogenase, carboxypeptidases A and B TABLE 6–1 Some Inorganic Elements That Serve as Cofactors for Enzymes Eduard Buchner, 1860–1917 James Sumner, 1887–1955 J. B. S. Haldane, 1892–1964 8885d_c06_190-237 1/27/04 7:13 AM Page 191 mac76 mac76:385_reb: