Enzymes in Biology and Catalysis

Enzymes in Biology

• Enzymes are biological catalysts - they accelerate the rate of chemical reactions without being consumed
• Most enzymes are globular proteins, with the exception of some RNA molecules
• Enzymes increase reaction rates by 10^20 times compared to uncatalyzed reactions

Catalytic Efficiency of Enzymes

• Enzymes lower the activation energy of a reaction, allowing it to reach equilibrium more rapidly
• Enzymes facilitate various organic reactions like ester hydrolysis, alcohol oxidation, and amide formation
• Enzymes operate under mild pH and temperature conditions, whereas lab-based reactions require harsh conditions
• Carbonic anhydrase, an enzyme involved in removing CO2, combines CO2 with water 36 million times per minute, significantly faster than without the enzyme

Enzyme Specificity

• Enzymes display high specificity for reactions and substrates
• Absolute specificity: catalyzes the reaction of only one substrate
• Relative specificity: catalyzes the reaction of structurally related substrates (e.g., lipases hydrolyze lipids)
• Stereochemical specificity: catalyzes the reaction of only one enantiomer (e.g., D-amino acid oxidase)

Enzyme Regulation

• Enzymes are meticulously regulated to ensure the controlled occurrence of necessary reactions within a cell
• Regulation methods include:
  • Activation of zymogens
  • Allosteric regulation
  • Genetic control

Enzyme Nomenclature

• Early enzymes were named with the suffix "-in," indicative of their protein nature (e.g., pepsin, trypsin)
• The Enzyme Commission (EC) system provides a standardized nomenclature for enzymes
• Enzymes are categorized into six main classes based on the reactions they catalyze
• Each enzyme has a unique, often long, systematic name that describes its substrate, functional group acted on, and type of reaction
• All EC names end in "-ase"
• Common names are often derived by adding "-ase" to the substrate name or a combination of substrate and reaction type

Enzyme Cofactors

• Conjugated proteins require non-protein molecules or metal ions known as prosthetic groups for functionality
• Tightly bound prosthetic groups are integral to the enzyme structure
• Weakly bound components that can be readily separated are called cofactors
• Organic cofactors are termed coenzymes
• Inorganic ions, like Mg²⁺, Zn²⁺, or Fe²⁺, can also act as cofactors
• The protein component of a conjugated protein is called an apoenzyme
• Many organic coenzymes are derived from vitamins
• Some substances naturally present in cells inhibit specific enzymes, providing internal regulation of cell metabolism

Enzyme Inhibition

• Irreversible inhibition occurs when an inhibitor forms a covalent bond with an enzyme, rendering it inactive
• Cyanide ion irreversibly inhibits cytochrome oxidase, halting cell respiration and leading to rapid death
• Heavy metals like mercury and lead bind to —SH groups on enzymes, potentially causing protein denaturation and neurological damage
• Chelating agents are used to treat heavy metal poisoning by binding to metal ions, allowing them to be excreted

Antibiotics as Enzyme Inhibitors

• Antibiotics inhibit essential life processes of certain bacteria
• Sulfa drugs interfere with folic acid synthesis in bacteria
• Penicillins inhibit transpeptidase, an enzyme involved in bacterial cell wall construction

Reversible Inhibition

• Reversible inhibitors bind reversibly to enzymes, establishing an equilibrium between bound and unbound forms
• When an inhibitor binds to an enzyme, the active site is blocked, inhibiting catalysis
• Reversal of inhibition can be achieved by shifting the equilibrium

Competitive Inhibitors

• Competitive inhibitors bind to the enzyme's active site, competing with substrate molecules
• They often resemble the structure of the normal substrate
• Sulfanilamide, a sulfa drug, competitively inhibits the enzyme involved in folic acid synthesis, leading to bacterial death
• Competitive inhibition can be reversed by increasing substrate concentration or decreasing enzyme concentration.

Noncompetitive Inhibitors

• Noncompetitive inhibitors bind to a site distinct from the active site, altering the enzyme's 3D conformation and interfering with substrate binding
• Noncompetitive inhibitors do not resemble substrate structures
• Increasing substrate concentration does not affect noncompetitive inhibition as the inhibitor binds to a separate site

Enzyme Regulation in Cellular Processes

• Enzyme activity is finely controlled to meet changing cellular needs
• Regulation mechanisms include:
  • Activation of zymogens
  • Allosteric regulation
  • Genetic control

Activation of Zymogens

• Zymogens or proenzymes are inactive precursors of enzymes
• Some enzymes are synthesized and stored in inactive forms to prevent damage to cellular structures
• Activation occurs when the zymogen is released and activated at the desired location
• Activation usually involves cleaving one or more peptide bonds
• Digestive enzymes like pepsin, trypsin, and chymotrypsin, as well as blood clotting enzymes, are activated in this manner

Allosteric Regulation

• Modulators, which are compounds that alter enzymes by changing their 3D conformation, can act as activators or inhibitors
• Enzymes with quaternary structures possessing binding sites for modulators are called allosteric enzymes
• Allosteric enzymes are often at key control points in cell processes
• Feedback inhibition occurs when the end product of a reaction sequence inhibits an earlier step, ensuring tight control of product concentration

Genetic Control of Enzyme Synthesis

• The production of all proteins and enzymes is genetically regulated by nucleic acids
• Genetic mechanisms can increase enzyme production
• Enzyme induction occurs when enzymes are synthesized in response to cellular needs
• Genetic control, coupled with allosteric regulation, provides robust control of cellular processes

Enzymes in Clinical Diagnosis

• Certain enzymes are specifically found in tissue cells
• Their presence in the bloodstream indicates tissue damage
• Serum enzyme concentration levels can be used to estimate the extent of damage
• Measuring enzyme concentrations in blood serum is a crucial diagnostic tool, particularly for diseases affecting the heart, liver, pancreas, prostate, and bones

Isoenzymes

• Isoenzymes are slightly different forms of the same enzyme produced by different tissues
• They catalyze the same reaction but differ structurally and have specific locations within the body
• Lactate dehydrogenase (LDH) consists of four subunits, with two types:
  • H subunit found in heart muscle cells
  • M subunit found in skeletal muscle cells
• Different combinations of H and M subunits result in different isoenzymes with tissue-specific functions

Explore the fascinating world of enzymes as biological catalysts that significantly speed up chemical reactions. Learn about their structure, function, and the specific roles they play in biological systems. This quiz covers enzyme efficiency, specificity, and various reactions they facilitate.