Part One

• Fundamental conditions of life

  • Organism must be able to self replicate
  • Organism must be able to catalyze chemical reactions effectively and selectively
• Without catalysis, chemical reactions could not occur on a useful time scale and it could not sustain life
• All reactions that occur in cells are catalyzed by enzymes
• Practical importance of studying enzymes

  • Some diseases, especially inheritable genetic disorders, are the result of a deficiency or even total absence of one or more enzymes
  • Other disease conditions may be caused by excessive activity of an enzyme
  • Measurements of the activities of enzymes in blood plasma, erythrocytes, or tissue samples are important in diagnosing certain illnesses
  • Many drugs act through interactions with enzymes
  • Enzymes are also important practical tools in chemical engineering, food technology, and agriculture
  • Virtually every process studied in a biochemical laboratory involves one or often many enzymes
• Enzymes

  • They are powerful biological catalysts
  • Rate accelerations by enzymes are often far greater than those by synthetic or inorganic catalysts
  • Like all catalysts, enzymes increase reaction rates, lowering reaction activation barriers
  • Enzymes do not affect the equilibria of reactions
• Enzymes

  • They exhibit a very high degree of specificity
  • Each enzyme catalyzes only one chemical reaction, or sometimes a few closely related reactions
  • Reaction activation barriers are thus lowered selectively
• Active sites

  • Specialized pockets where enzymatic reactions occur
  • Similar to ligand binding sites, except that a reaction occurs there - the conversion of a substrate, a molecule that is acted on by an enzyme, to a product
• Catalytic power of enzymes

  • Enzymes bind most tightly to the transition state of the catalyzed reaction, using binding energy to lower the activation barrier
  • Enzyme active sites are organized by evolution to facilitate multiple mechanisms of chemical catalysis simultaneously
• Enzyme regulation

  • Regulatory mechanisms include reversible covalent modification, binding of allosteric modulators, proteolytic activation, noncovalent binding to regulatory proteins, and elaborate regulatory cascades
  • Enzymes are often subject to multiple methods of regulation, which allows for exquisite control of every chemical process that occurs in the cell
• Power of enzyme catalysts

  • Orotidine phosphate decarboxylase, an enzyme involved in the biosynthesis of pyrimidine nucleotides, has a rate of enhancement of 10^17
  • The uncatalyzed reaction has a half life of 78 million years
  • For the enzyme, the reaction occurs in milliseconds
• Enzymes

  • With the exception of a few catalytic RNA molecules, enzymes are proteins
  • Their catalytic activity depends on the integrity of their native protein conformation
  • If an enzyme is denatured or dissociated into its subunits, catalytic activity is usually lost
  • The catalytic activity of each enzyme is intimately linked to the primary, secondary, tertiary, and quaternary protein structure
• Enzyme molecular weights

  From about 12,000 to more than 1 million
• Enzyme cofactors and coenzymes

  • Cofactors are one or more inorganic ions, such as Fe2+, Mg2+, Mn2+, or Zn2+
  • Coenzymes are complex organic or metallorganic molecules that act as transient carriers of functional groups
  • Most coenzymes are derived from vitamins, or organic nutrients required in small amounts in the diet
  • Some enzymes require both a cofactor and a coenzyme to function
• Prosthetic group


  A coenzyme or metal ion that is very tightly or covalently bound to an enzyme
• Holoenzyme

  A complete, catalytically active enzyme together with its bound coenzyme and/or metal ions
• Apoenzyme or apoprotein


  The protein part of a holoenzyme
• Enzyme modifications

  • Some enzymes are modified covalently by phosphorylation, glycosylation, etc.
  • Many of these alterations are involved in the regulation of enzyme activity
• Inorganic ions that serve as cofactors for enzymes

  • Cu2+ for cytochrome oxidase
  • Fe2+ and Fe3+ for cytochrome oxidase, catalase, and peroxidase
  • K+ for pyruvate kinase
  • Mg2+ for hexokinase, glucose 6-phosphatase, and pyruvate kinase
  • Mn2+ for arginase and ribonucleotide reductase
  • Mo for dinitrogenase
  • Ni2+ for urease
  • Zn2+ for carbonic anhydrase, alcohol dehydrogenase, carboxypeptidases A and B
• Coenzymes that serve as transient carriers of specific atoms or functional groups


  • Biocytin transfers CO2 and is a dietary precursor to biotin, or vitamin B7
  • Coenzyme A transfers acyl groups and is a dietary precursor to pantothenic acid, vitamin B5, and other compounds
  • 5'-deoxyadenosylcobalamin, or coenzyme B12, transfers H atoms and alkyl groups and is a dietary precursor to vitamin B12
  • Flavin adenine dinucleotide transfers electrons and is a dietary precursor to riboflavin, vitamin B2
  • Lipoate transfers electrons and acyl groups
  • Nicotinamide adenine dinucleotide transfers anhydride ions and is a dietary precursor to niacin, or vitamin B3
  • Pyridoxal phosphate transfers amino groups and is a dietary precursor to pyridoxine, or vitamin B6
  • Tetrahydrofolate transfers one carbon groups and is a dietary precursor to folate, or vitamin B9
  • Thiamine pyrophosphate transfers aldehydes and is a dietary precursor to thiamine, or vitamin B1
• Enzyme classification

  • Many enzymes have been named by adding the suffix -ase to the name of their substrate or to a word or phrase describing their activity
  • Other enzymes were named by their discoverers for a broad function, before the specific reaction catalyzed was known
  • Other enzymes were named for their source
  • Sometimes the same enzyme has two or more names or two different enzymes have the same name
  • To limit ambiguity, biochemists worldwide have adopted a system for naming and classifying enzymes, dividing them into seven classes based on the type of reaction catalyzed, with each assigned a four part classification number and a systemic name
  • For many enzymes, the trivial name is more frequently used
  • The names of thousands of enzymes is maintained by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology
• Seven classes of enzymes

  • Class 1 - Oxidoreductases, catalyze the transfer of electrons
  • Class 2 - Transferases, catalyze group transfer
  • Class 3 - Hydrolases, catalyze hydrolysis
  • Class 4 - Lyases, catalyze the cleavage of C-C, C-O, C-N, or other bonds by elimination, leaving double bonds or rings, or addition of groups to double bonds
  • Class 5 - Isomerases, catalyze the transfer of groups within molecules to yield isomeric forms
  • Class 6 - Ligases, catalyze the formation of C-C, C-S, C-O, and C-N bonds by condensation reactions coupled to cleavage of ATP or similar cofactors
  • Class 7 - Translocases, catalyze the movement of molecules or ions across membranes or their separation within membranes