Enzymes and Their Mechanisms

Enzymes

• Enzymes are biological catalysts that speed up the rate of thermodynamically favorable biological reactions.
• They accelerate reactions without altering the reaction equilibrium, being consumed in the overall reaction, and are required in small quantities.
• Enzymes are highly specific for their substrate, possessing active sites.

Enzyme Structure

• Enzymes are mostly three-dimensional globular proteins with tertiary and quaternary structure.
• Some RNA species enzymes are called Ribozymes.

Active Site

• The active site is a specialized region where a substrate can fit precisely, facilitating chemical reactions.
• The amino acids R-groups (side chains) in the active site contribute to the specific chemical environment that favors the reaction.

Substrate

• The substrate is the molecule that an enzyme reacts with and binds to the active site.
• Enzymes are specific to their substrates, determined by the active site.

Apoenzyme, Coenzyme, Holoenzyme

• Apoenzyme is the protein part of a conjugated enzyme.
• Coenzyme (Cofactor) is the non-protein part of a conjugated enzyme.
• Holoenzyme is the biochemically active conjugated enzyme, consisting of both the protein and non-protein parts.

Enzyme Nomenclature

• Enzymes are named according to the type of reaction they catalyze and/or their substrate.
• The suffix "ase" is often used for enzymes, with a prefix denoting the type of reaction the enzyme catalyzes (e.g., oxidase, hydrolase).

Major Classes of Enzymes

• Oxidoreductases: Catalyze oxidation/reduction reactions, acting on chemical groupings to add or remove hydrogen atoms. Examples: oxidase, reductase, dehydrogenase.
• Transferases: Transfer functional groups (e.g., methyl or phosphate) between donor and acceptor molecules. Examples: transaminases, kinases.
• Hydrolases: Catalyze the hydrolysis of various bonds, adding water across a bond. Examples: lipase, proteases, nucleases, carbohydrases, phosphatases.
• Lyases: Cleave various bonds by means other than hydrolysis and oxidation, adding or removing water, ammonia, or carbon dioxide across double bonds. Examples: dehydratases, decarboxylases, deaminases, hydratase.
• Isomerases: Catalyze isomerization changes within a single molecule. Examples: mutase reactions, racemases.
• Ligases: Join two molecules with covalent bonds, catalyzing reactions where two chemical groups are joined (or ligated) using energy from ATP. Examples: synthetases, carboxylases.

Factors Affecting Enzyme Activity

• Temperature: Increased temperature generally increases enzyme kinetics due to more collisions and increased reaction rate.
• pH: Most enzymes are active over a narrow pH range, with optimal activity at a specific pH (pHOPT). Changes in pH can lead to denaturation and loss of function.
• Substrate Concentration: Increased substrate concentration increases reaction rate until a saturation point is reached where the reaction rate remains constant despite further substrate increase.
• Enzyme Concentration: Increased enzyme concentration increases reaction rate, with a greater enzyme concentration resulting in a higher reaction rate.

Enzyme Inhibition

• Inhibition: A substance that slows down or stops the normal catalytic function of an enzyme.
• Types of Inhibition:
  • Reversible Competitive Inhibition: Inhibitor binds reversibly to the active site, competing with the substrate. Increasing substrate concentration can overcome inhibition.
  • Reversible Non-competitive Inhibition: Inhibitor binds to a site other than the active site, changing the enzyme's conformation and reducing its activity. Increased substrate concentration cannot overcome inhibition.
  • Irreversible Inhibition: Inhibitor binds irreversibly to the enzyme, permanently inactivating it.

Medical Applications of Enzymes

• Lactate dehydrogenase (LDH): Increased levels in the blood indicate myocardial infarction (heart attack).
• Tissue plasminogen activator (TPA): Activates plasminogen, which dissolves blood clots. Used in the treatment of MI.

Enzymes as Therapeutic Agents (Drugs)

• Streptokinase: Clot lysis in myocardial infarction, trauma, and bleeding.
• Asparaginase: Acute lymphocytic leukemia.
• Adenosine deaminase: Severe combined immunodeficiency syndrome (SCID).

Enzymes as Drug Targets

• Dihydrofolate reductase: Antifolates such as methotrexate (cancer) and pyrimethamine (protozoa, malaria).
• Xanthine oxidase: Allopurinol (hyperuricemia, gout).
• Thymidylate synthase: 5-Fluorouracil & 5-fluorodeoxyuridine (cancer).
• Glycopeptide transpeptidase: Antibiotics, penicillin.
• HIV-Reverse transcriptase: 3′-azido-2′,3′-dideoxythymidine (AZT).
• HIV & SARS proteases: Ritonavir, saquinavir (clinical trial phase).

Michaelis-Menten Equation

• Describes the relationship between the rate of an enzyme-catalyzed reaction and the substrate concentration.

Km and Vmax Values

• Km: A measure of an enzyme's affinity for its substrate. Lower Km indicates a higher affinity, and higher Km indicates a lower affinity.
• Vmax: The maximum rate of an enzyme-catalyzed reaction. It is determined by the enzyme's turnover number (substrate molecules converted to product per unit time).

Lineweaver-Burke Plot for Competitive Inhibition

• Competitive inhibitors do not change the Vmax of enzyme reactions.
• They increase the apparent Km value because they bind reversibly to the active site.
• Increasing substrate concentration can overcome their inhibition.
• Unchanged Vmax and increased Km reflect the effects of competitive inhibition.

What are Enzymes?

• Enzymes are biocatalysts that accelerate the rate of thermodynamically favorable biological reactions.
• Their catalytic power can be thousands to millions of times faster than non-catalyzed reactions.

Importance of Enzymes

• Enzymes are essential for virtually all biological processes.
• They act as catalysts, speeding up reactions without being consumed in the process.

Activation Energy

• It's the minimum amount of energy required for a reaction to occur.
• Enzymes lower activation energy, making reactions proceed faster.

Properties of Enzymes

• Most enzymes are three-dimensional globular proteins.
• Some special RNA species act as enzymes and are called Ribozymes.

General Properties of Enzymes

• Enzymes accelerate reactions but don't alter the reaction equilibrium.
• They are not consumed during reactions.
• They are required in small quantities.
• Enzymes exhibit high catalytic power.
• They show specificity for their substrates.
• Enzymes possess active sites.

Active Site

• It's a specialized region on an enzyme where the substrate binds.
• Provides optimal conditions for substrate conversion.

Substrate

• The molecule that an enzyme reacts with.
• Binds to the active site of an enzyme.
• Enzymes are specific to their substrates.

Enzyme Structure

• Enzymes can be simple proteins or conjugated proteins.
• Conjugated enzymes consist of an apoenzyme (protein part) and a coenzyme (non-protein part).

Enzyme Nomenclature

• Enzymes are named according to the type of reaction they catalyze or their substrate.
• Many digestive enzymes have the suffix "-in" (e.g., pepsin, trypsin).
• Most other enzymes have the suffix "-ase" (e.g., lactase, amylase, lipase).

Six Major Classes of Enzymes

• Oxidoreductases: Catalyze oxidation-reduction reactions.
• Transferases: Transfer functional groups between molecules.
• Hydrolases: Catalyze the hydrolysis of various bonds.
• Lyases: Cleave bonds by means other than hydrolysis and oxidation.
• Isomerases: Catalyze isomerization within a single molecule.
• Ligases: Join two molecules with covalent bonds.

Enzyme-Substrate Complex

• When a substrate binds to an enzyme's active site, a temporary Enzyme-Substrate Complex forms.
• This complex facilitates the chemical reaction.

Lock & Key Model

• Proposes that the active site of an enzyme has a rigid shape complementary to the substrate.
• Similar to a key fitting into a lock.

Induced Fit Model

• Recognizes that enzymes are flexible and can change shape upon substrate binding.
• The active site adjusts its shape to accommodate the substrate.

Specificity of Enzymes

• Enzymes display various levels of specificity for their substrates:
• Absolute Specificity: Enzyme acts on only one specific substrate.
• Group Specificity: Enzyme acts on similar substrates with a specific functional group.
• Linkage Specificity: Enzyme acts on a specific type of chemical bond, regardless of the rest of the molecule.
• Stereochemical Specificity: Enzyme distinguishes between stereoisomers (e.g. L-amino acids vs. D-amino acids).

Factors Affecting Enzymes

• Temperature: Enzyme activity generally increases with temperature until an optimal point is reached. Beyond that, heat denatures the enzyme and reduces activity.
• pH: Each enzyme has an optimal pH range. Small changes in pH can lead to denaturation and loss of activity.
• Substrate Concentration: Enzyme activity increases with substrate concentration until saturation is reached. At saturation, further increases in substrate concentration have no effect.
• Enzyme Concentration: As enzyme concentration increases, so does the reaction rate.

Michaelis-Menten Equation

• Describes the relationship between reaction rate and substrate concentration.
• Explains how reaction rate increases initially but levels off due to enzyme saturation.

Km and Vmax Values

• Km: A measure of an enzyme's affinity for its substrate. Lower Km indicates higher affinity.
• Vmax: The maximum rate of an enzyme-catalyzed reaction. It's determined by the enzyme's turnover number.

Enzyme Inhibition

• A substance that slows down or stops the normal catalytic function of an enzyme by binding to the enzyme.
• Competitive Inhibition: Inhibitor binds to the active site, competing with the substrate. Can be overcome by increasing substrate concentration.
• Noncompetitive Inhibition: Inhibitor binds to a site other than the active site, changing the enzyme's conformation and reducing its activity. Not affected by increasing substrate concentration.
• Uncompetitive Inhibition: Inhibitor binds only to the enzyme-substrate complex. Decreases both Vmax and Km.

Lineweaver-Burke Plot

• Used to graphically represent enzyme kinetics and analyze different types of inhibition.
• X-axis: 1/[S] (reciprocal of substrate concentration)
• Y-axis: 1/V (reciprocal of reaction rate)

Allosteric Site

• It's a regulatory site on an enzyme, distinct from the active site, where effector molecules can bind.
• Positive Allosteric Regulation: Binding of the effector increases enzyme activity.
• Negative Allosteric Regulation: Binding of the effector decreases enzyme activity.

Enzyme Definition and Nomenclature

• Enzymes are biological catalysts that speed up chemical reactions without being consumed in the process.
• Enzymes are named based on the type of reaction they catalyze and/or their substrate.
• Most enzymes end in "-ase" (e.g., lactase, amylase, lipase).
• Some digestive enzymes end in "-in" (e.g., pepsin, trypsin, chymotrypsin).
• Prefixes denote the type of reaction the enzyme catalyzes (e.g., oxidase for redox reactions, hydrolase for hydrolysis).

6 Major Classes of Enzymes

• Oxidoreductases: Catalyze oxidation-reduction reactions (e.g., oxidase, reductase, dehydrogenase).
• Transferases: Transfer functional groups between molecules (e.g., transaminases, kinases).
• Hydrolases: Catalyze hydrolysis reactions by adding water across a bond (e.g., lipase, protease, nuclease, carbohydrases, phosphatases).
• Lyases: Cleave bonds using mechanisms other than hydrolysis or oxidation (e.g., dehydratases, decarboxylases, deaminases, hydratase).
• Isomerases: Catalyze isomerization changes within a single molecule (e.g., mutases, racemases, isomerases).
• Ligases: Join two molecules with covalent bonds using ATP energy (e.g., synthetases, carboxylases).

Enzyme-Substrate Complex

• When a substrate binds to an enzyme's active site, an enzyme-substrate complex is formed.
• This complex allows the substrate to undergo its chemical reaction much faster.

Lock and Key Model of Enzyme Action

• The active site has a rigid shape, like a lock, and the substrate fits into it like a key.
• The substrate binds to the active site, undergoes its reaction, and then the products are released.

Induced Fit Model of Enzyme Action

• Enzymes are flexible and constantly change their shape.
• The shape of the active site adapts to accommodate the substrate upon binding.

Specificity of Enzymes

• Absolute specificity: The enzyme catalyzes a particular reaction for only one substrate (e.g., catalase for hydrogen peroxide, urease for urea).
• Group specificity: The enzyme acts only on similar substrates with a specific functional group (e.g., carboxypeptidase on amino acids, hexokinase on hexoses).
• Linkage specificity: The enzyme acts on a particular type of chemical bond, regardless of the rest of the molecular structure (e.g., phosphatases on phosphate-ester bonds, chymotrypsin on peptide bonds).
• Stereochemical specificity: The enzyme can distinguish between stereoisomers (e.g., L-amino-acid oxidase catalyzes reactions of L-amino acids, not D-amino acids).

Factors Affecting Enzymes

• Temperature: Increased temperature generally increases enzyme activity until an optimal temperature is reached, after which activity decreases due to denaturation.
• pH: Most enzymes have an optimal pH range, outside of which their activity decreases due to changes in protein structure.
• Substrate concentration: Increased substrate concentration increases reaction rate until the active sites are saturated, after which the rate plateaus.
• Enzyme concentration: Increased enzyme concentration increases reaction rate.

Michaelis-Menten Equation

• Describes the relationship between substrate concentration and reaction rate.

Km and Vmax Values

• Km: A measure of an enzyme's affinity for its substrate. Lower Km indicates higher affinity.
• Vmax: The maximum rate of an enzyme-catalyzed reaction, determined by the enzyme's turnover number.

Enzyme Inhibition

• Competitive Inhibition: A reversible inhibitor that binds to the active site, competing with the substrate. Can be overcome by increasing substrate concentration.
• Noncompetitive Inhibition: A reversible inhibitor that binds to a site other than the active site, reducing the enzyme's efficiency. Cannot be overcome by increasing substrate concentration.
• Uncompetitive Inhibition: A reversible inhibitor that binds to the enzyme-substrate complex, decreasing both Vmax and Km.

Allosteric Site

• A regulatory site on an enzyme that binds effectors, which can either activate or inhibit enzyme activity.
• Positive Allosteric Regulation: The effector increases the enzyme's affinity for the substrate.
• Negative Allosteric Regulation: The effector decreases the enzyme's affinity for the substrate.

Drugs Inhibiting Enzyme Activity

• ACE Inhibitors: Inhibit angiotensin-converting enzyme, lowering blood pressure.
• Penicillin: Inhibits transpeptidase, weakening bacterial cell walls and killing bacteria.

Medical Uses Of Enzymes

• Lactate Dehydrogenase (LDH): Increased levels in blood can indicate myocardial infarction (heart attack).
• Tissue Plasminogen Activator (TPA): Activates plasminogen, dissolving blood clots and used to treat MI.

Therapeutic Uses of Enzymes

• Streptokinase: Used to break down blood clots in cases of myocardial infarction, trauma, or bleeding.
• Asparaginase: Used as an anti-cancer agent, particularly for acute lymphocytic leukemia.
• Adenosine Deaminase: Used to treat severe combined immunodeficiency syndrome (SCID).

Enzymes as Drug Targets

• Dihydrofolate Reductase: Targeted by antifolate drugs like methotrexate (cancer) and pyrimethamine (malaria).
• Xanthine Oxidase: Targeted by allopurinol for hyperuricemia and gout.
• Thymidylate Synthase: Targeted by anticancer drugs 5-fluorouracil and 5-fluorodeoxyuridine.
• Glycopeptide Transpeptidase: Targeted by antibiotics like penicillin.
• HIV-Reverse Transcriptase: Targeted by antiretroviral drugs like AZT.
• HIV and SARS Proteases: Targeted by antiviral drugs like ritonavir and saquinavir.

What are Enzymes?

• Enzymes are biocatalysts
• Enzymes increase the rate of biological, thermodynamically favorable reactions by thousands or millions of times

Importance of Enzymes

• No biological reactions work without enzymes

Activation Energy

• The minimum amount of energy required for a reaction to start

Properties of Enzymes

• Most enzymes are three-dimensional globular proteins
• Some enzymes are special RNA species called ribozymes

General Properties of Enzymes

• Enzymes speed up reactions without altering the equilibrium
• Enzymes are not used up in the reaction
• Small quantities of enzymes are required
• Enzymes have significant power for catalysis
• Enzymes are highly specific to their substrates
• Enzymes contain active sites

Active Site

• The active site of an enzyme is a specialized region where a substrate binds precisely
• This microenvironment facilitates and accelerates chemical reactions by providing optimal conditions for substrate conversion
• Active sites are made of amino acids' R-groups (side chains)

Substrate

• The substrate is the molecule that an enzyme reacts with
• The substrate binds to the active site of the enzyme and is the substance that is changed during a reaction
• Enzymes are specific to their substrates and the specificity is determined by the active site

Enzyme Structure

• Enzymes can have different levels of structure: primary, secondary, tertiary, and quaternary

Enzyme Definition

• Apoenzyme: The protein portion of a conjugated enzyme
• Coenzyme (Cofactor): The non-protein portion of a conjugated enzyme
• Holoenzyme: The biochemically active conjugated enzyme (includes both the protein and non-protein parts)

Enzyme Nomenclature

• Enzymes are named based on the reaction they catalyze or their substrate
• Many digestive enzymes have the suffix "-in" - ex. pepsin, trypsin, chymotrypsin
• Most other enzyme names end with "-ase" -- ex. lactase, amylase, lipase, protease
• The prefix of an enzyme name refers to the type of reaction:
  • Oxidase: redox reaction
  • Hydrolase: addition of water to break a component into two parts

6 Major Classes of Enzymes

• EC 1. Oxidoreductases
  • Catalyze oxidation/reduction
    • Oxidase: oxidation of substrate
    • Reductase: reduction of substrate
    • Dehydrogenase: introduction of a double bond by removing two hydrogen atoms
• EC 2. Transferases
  • Transfer functional groups (e.g. methyl or phosphate) between molecules
    • Transaminases: transfer of an amino group
    • Kinases: transfer of a phosphate group
• EC 3. Hydrolases
  • Catalyze the hydrolysis of various bonds by adding water across a bond
    • Lipase: hydrolysis of ester linkages in lipids
    • Proteases: hydrolysis of amide linkages in proteins
    • Nucleases: hydrolysis of sugar phosphate ester bonds in nucleic acids
    • Carbohydrases: hydrolysis of glycosidic bonds in carbohydrates
    • Phosphatases: hydrolysis of phosphate-ester bonds
• EC 4. Lyases
  • Cleave various bonds by means other than hydrolysis or oxidation
  • Add water, ammonia, or carbon dioxide across double bonds or remove these elements to produce double bonds
    • Dehydratases: removal of H2O from substrate
    • Decarboxylases: removal of CO2 from substrate
    • Deaminases: removal of NH3 from substrate
    • Hydratase: addition of H2O to a substrate
• EC 5. Isomerases
  • Catalyze isomerization changes within a single molecule
    • Mutase reactions: shift chemical groups
    • Racemases: convert D to L isomers or vice versa
• EC 6. Ligases
  • Catalyze the joining of two molecules, often coupled with the hydrolysis of ATP

Michaelis-Menten Equation

• Describes the relationship between the rate of an enzyme-catalyzed reaction and substrate concentration

Km and Vmax Values

• Km is a measure of an enzyme's affinity for its substrate:
  • A lower Km indicates higher affinity
  • A higher Km indicates lower affinity
• Vmax is the maximum rate of an enzyme reaction:
  • It is determined by the enzyme's turnover number (substrate molecules converted per unit time)

Enzyme Inhibition

• A substance that slows down or stops the normal catalytic function of an enzyme by binding to it
• Three types of inhibition:
  • Reversible competitive inhibition
  • Reversible noncompetitive inhibition
  • Irreversible inhibition

Competitive Inhibition

• The inhibitor binds reversibly to the active site of the enzyme
• Increasing substrate concentration can overcome this inhibition
• Unchanged Vmax but increased Km reflects the effects of competitive inhibition

Noncompetitive Inhibition

• The inhibitor binds to a site other than the active site
• The inhibitor reduces the concentration of the enzyme-substrate (ES) complex
• Vmax decreases, but Km remains unchanged

Uncompetitive Inhibition

• The inhibitor binds to the enzyme-substrate complex
• Decreases both Vmax and Km
• Cannot be reversed by increasing substrate concentration

Allosteric Site

• The regulatory site of an enzyme that binds to effector or non-substrate molecules
• Allosteric sites can activate or inhibit enzyme activity

Types of Allosteric Regulation

• Positive Allosteric Regulation: Binding of the effector increases enzyme activity by increasing its affinity to the substrate
• Negative Allosteric Regulation: Binding of the effector decreases enzyme activity by decreasing the affinity for the substrate

Drugs Inhibiting Enzyme Activity

• ACE Inhibitors: inhibit angiotensin-converting enzyme, lowers blood pressure
• Penicillins: β-lactam antibiotics that inhibit transpeptidase
  • Transpeptidase strengthens the cell wall of bacteria
  • Penicillin weakens the cell wall, causing the bacteria to die

Medical Uses of Enzymes

• Lactate dehydrogenase (LDH): Increased levels in the blood indicate myocardial infarction (heart attack)
• Tissue plasminogen activator (TPA): Activates plasminogen, which dissolves blood clots. Used in MI treatment.

Enzymes as Therapeutic Agents (Drugs)

• Streptokinase: Clot lysis, in myocardial infarction, trauma, or bleeding
• Asparaginase: Acute lymphocytic leukemia
• Adenosine Deaminase: Severe combined immunodeficiency syndrome (SCID)

Enzymes as Drug Targets

• Dihydrofolate reductase: Antifolates like methotrexate (cancer) and pyrimethamine (protozoa & malaria)
• Xanthine oxidase: Allopurinol for hyperuricemia and gout
• Thymidylate synthase: 5-Fluorouracil and 5-fluorodeoxyuridine (cancer)
• Glycopeptide transpeptidase: Antibiotics, penicillin
• HIV-Reverse transcriptase: 3’-azido-2’,3’-dideoxythymidine (AZT)
• HIV & SARS proteases: Ritonavir and saquinavir (clinical trials)

Enzymes

• Enzymes are biocatalysts that increase the rate of thermodynamically favorable biological reactions.
• They can accelerate reactions by several thousand to million folds.
• Enzymes are essential for life and are involved in virtually every biological process.

Importance of Enzymes

• Enzymes are biological catalysts, meaning they speed up reactions without being consumed in the process.
• They are crucial for vital processes like metabolism, digestion, and DNA replication.

Activation Energy

• Activation energy is the minimum energy required for a reaction to occur.
• Enzymes lower the activation energy, making reactions happen faster.

Properties of Enzymes

• Most enzymes are globular proteins with tertiary and quaternary structures.
• Some special RNA molecules called ribozymes also have enzymatic activity.

General Properties of Enzymes

• Enzymes accelerate reactions but do not alter the equilibrium of the reaction.
• They are not consumed during the reaction.
• They are required in small quantities.
• Enzymes have high catalytic power, meaning they can accelerate reactions significantly.
• Enzymes are highly specific for their substrates.
• Enzymes have active sites.

Active Site

• The active site is a specific region on an enzyme where the substrate binds.
• The active site provides an optimal environment for the substrate to be converted into a product.

Substrate

• The substrate is the molecule that an enzyme reacts with.
• It binds to the active site of the enzyme.
• The specificity of an enzyme is determined by the active site, which fits only specific substrates.

Apoenzyme, Coenzyme, Holoenzyme

• An apoenzyme is the protein part of a conjugated enzyme.
• A coenzyme is the non-protein part of a conjugated enzyme.
• A holoenzyme is the biochemically active conjugated enzyme formed by the combination of an apoenzyme and a coenzyme.

Enzyme-Substrate Complex

• When a substrate binds to the active site of an enzyme, an enzyme-substrate complex is formed temporarily.
• This complex allows the substrate to undergo its chemical reaction much faster.

Lock and Key Model of Enzyme Action

• The active site has a rigid shape (the lock), and the substrate (the key) must fit exactly into it.
• This model explains the specificity of enzymes.

Induced Fit Model of Enzyme Action

• Many enzymes are flexible and change shape constantly.
• The shape of the active site changes to accommodate the substrate, fitting it like a hand in a glove.

Specificity of Enzymes

• Enzymes can be categorized based on their specificity:
  • Absolute Specificity: An enzyme catalyzes a particular reaction for only one substrate.
  • Group Specificity: An enzyme acts only on similar substrates that have a specific functional group.
  • Linkage Specificity: An enzyme acts on a particular type of chemical bond, regardless of the rest of the molecular structure.
  • Stereochemical Specificity: An enzyme can distinguish between stereoisomers.

Factors Affecting Enzymes

• Various factors can affect the activity of an enzyme:

  • Temperature: Increasing temperature increases the rate of an enzyme-catalyzed reaction until a certain point, after which the enzyme denatures and loses activity.
  • pH: Each enzyme has an optimal pH range for activity.
  • Substrate Concentration: Increasing substrate concentration increases the reaction rate until the enzyme becomes saturated.
  • Enzyme Concentration: Increasing enzyme concentration increases the reaction rate.

Michaelis-Menten Equation

• The Michaelis-Menten equation describes the relationship between the rate of an enzyme-catalyzed reaction and the substrate concentration.

Km and Vmax Values

• Km: The Michaelis constant, which is a measure of an enzyme's affinity for its substrate. A lower Km indicates a higher affinity, while a higher Km indicates a lower affinity.
• Vmax: The maximum rate of an enzyme-catalyzed reaction. It is determined by the enzyme's turnover number (the number of substrate molecules converted to product per unit time).

Enzyme Inhibition

• A substance that slows down or stops the normal catalytic function of an enzyme by binding to the enzyme. Types of inhibition:

  • Reversible Competitive Inhibition: The inhibitor competes with the substrate for the active site.
  • Reversible Non-competitive Inhibition: The inhibitor binds to a site on the enzyme other than the active site, altering the enzyme's shape and reducing its activity.
  • Irreversible Inhibition: The inhibitor binds permanently to the enzyme, causing permanent inactivation.

Allosteric Site

• The allosteric site is a regulatory site on an enzyme where effectors bind to either activate or inhibit the enzyme's activity.

Types of Allosteric Regulation

• Positive Allosteric Regulation: Binding of the effector increases the enzyme's affinity for the substrate, leading to an increase in enzyme activity.
• Negative Allosteric Regulation: Binding of the effector decreases the enzyme's affinity for the substrate, leading to a decrease in enzyme activity.

Drugs Inhibiting Enzyme Activity

• Many drugs work by inhibiting specific enzymes to treat various diseases:

  • ACE Inhibitors: Inhibit Angiotensin-Converting Enzyme (ACE) to lower blood pressure.
  • Penicillin: Inhibits transpeptidase, an enzyme that strengthens bacterial cell walls, leading to bacterial death.

Medical Uses of Enzymes

• Enzymes play important roles in diagnosis and treatment of various diseases:
  • Lactate Dehydrogenase (LDH): Increased levels in blood indicate myocardial infarction (heart attack).
  • Tissue Plasminogen Activator (TPA): Activates plasminogen, an enzyme that dissolves blood clots, used in the treatment of myocardial infarction (heart attack).

Enzymes as Therapeutic Agents

• Some enzymes can be used as therapeutic agents (drugs) to treat various medical conditions:

  • Streptokinase: Used for clot lysis in myocardial infarction, trauma, and bleedings.
  • Asparaginase: Used for acute lymphocytic leukemia.
  • Adenosine Deaminase: Used for treatment of Severe Combined Immuno-deficiency Syndrome (SCID).

Enzymes as Drug Targets

• Many enzymes are targeted by drugs to treat various diseases:

  • Dihydrofolate Reductase: Targeted by antifolates like methotrexate (cancer) and pyrimethamine (protozoa, malaria).
  • Xanthine Oxidase: Targeted by allopurinol for hyperuricemia and gout.
  • Thymidylate Synthase: Targeted by 5-fluorouracil and 5-fluorodeoxyuridine for cancer treatment.
  • Glycopeptide Transpeptidase: Targeted by antibiotics like penicillin.
  • HIV-Reverse Transcriptase: Targeted by 3'-azido-2',3'-dideoxythymidine (AZT).
  • HIV & SARS Proteases: Targeted by ritonavir and saquinavir (clinical trial phase).

Enzymes: Biocatalysts

• Enzymes are biological catalysts that accelerate the rate of thermodynamically favorable reactions by several thousand to million folds.
• Enzymes are essential for all biological processes.
• Catalysts are chemical substances that speed up reactions but are not used up in the process.
• The activation energy of a reaction is the required input of energy to make a reaction start.

Enzyme Characteristics

• Most enzymes are globular proteins with tertiary and quaternary structures.
• Some enzymes are RNA molecules known as ribozymes.
• Enzymes accelerate reactions without altering the equilibrium.
• They are not consumed in the reaction and are required in small quantities.
• Enzymes exhibit high specificity for their substrates.
• Enzymes possess active sites, specialized regions where substrates bind precisely.
• The active site facilitates and accelerates chemical reactions by providing optimal conditions for substrate conversion.

Enzyme Nomenclature

• Enzymes are named according to the type of reaction they catalyze and/or their substrate.
• The suffix "ase" is commonly used for enzyme names, with a prefix indicating the type of reaction catalyzed (e.g., oxidase, hydrolase).

Enzyme Classification

• Enzymes are categorized into six major classes based on their catalytic activity:

  Oxidoreductases

  • Catalyze oxidation-reduction reactions
  • Act on various chemical groupings to add or remove hydrogen atoms.
  • Examples: oxidases, reductases, dehydrogenases.

  Transferases

  • Catalyze the transfer of functional groups between donor and acceptor molecules.
  • Examples: transaminases, kinases.

  Hydrolases

  • Catalyze the hydrolysis of various bonds by adding water across the bond.
  • Degrade complex molecules into simpler units.
  • Examples: lipases, proteases, nucleases, carbohydrases, phosphatases.

  Lyases

  • Catalyze the cleavage of various bonds by means other than hydrolysis and oxidation.
  • Can add elements like water, ammonia, or carbon dioxide across double bonds or remove them to produce double bonds.
  • Examples: dehydratases, decarboxylases, deaminases, hydratases.

  Isomerases

  • Catalyze isomerization changes within a single molecule.
  • Rearrange atoms within a molecule without changing the overall composition.
  • Examples: mutases.

  Ligases

  • Join two molecules together, often with the help of ATP.
  • Form new bonds between molecules.
  • Examples: synthetases.

Enzyme Activity

• The Michaelis-Menten equation describes the relationship between the rate of an enzyme-catalyzed reaction and the substrate concentration.

Enzyme Kinetics

• Km: A measure of an enzyme's affinity for its substrate.
  • Lower Km indicates a higher affinity.
  • Higher Km indicates a lower affinity.
• Vmax: The maximum rate of an enzyme-catalyzed reaction.
  • Determined by the enzyme's turnover number (the number of substrate molecules converted to product per unit time).

Enzyme Inhibition

• Inhibition: A substance that slows down or stops the normal catalytic function of an enzyme by binding to the enzyme.
• Reversible Inhibition: The inhibitor binds reversibly to the enzyme and can be overcome by increasing substrate concentration.
  • Competitive Inhibition: The inhibitor binds to the active site of the enzyme, competing with the substrate for binding.
  • Noncompetitive Inhibition: The inhibitor binds to a site other than the active site, altering both the enzyme's affinity for the substrate and its ability to catalyze the reaction.
• Uncompetitive Inhibition: The inhibitor binds only to the enzyme-substrate complex, decreasing both Vmax and Km.
• Irreversible Inhibition: The inhibitor binds permanently to the enzyme, inactivating it.

Allosteric Control

• Allosteric Site: A regulatory site on an enzyme that binds to effector molecules.
  • Positive Allosteric Regulation: The effector increases the enzyme's affinity for the substrate, leading to an increase in enzyme activity.
  • Negative Allosteric Regulation: The effector decreases the enzyme's affinity for the substrate, leading to a decrease in enzyme activity.

Medical Uses of Enzymes

• Therapeutic Agents: Enzymes can be used as drugs for various diseases.
• Diagnostic Markers: Enzyme levels in blood can be used to diagnose certain conditions.
• Drug Targets: Enzymes are often targets for drugs designed to treat diseases.

Examples of Enzyme Inhibition by Drugs

• ACE Inhibitors: Inhibit the angiotensin-converting enzyme (ACE), lowering blood pressure.
• Penicillin: Inhibits transpeptidase, an enzyme that strengthens bacterial cell walls, leading to weakened cell walls and bacterial death.

Examples of Enzyme Use in Medicine

• Lactate Dehydrogenase (LDH): High levels in blood indicate myocardial infarction (heart attack).
• Tissue Plasminogen Activator (TPA): Dissolves blood clots by activating plasminogen. Used in the treatment of MI.

Explore the fascinating world of enzymes in this quiz, covering their role as biological catalysts and their unique structures. Test your knowledge on enzyme specificity, active sites, and the differences between apoenzymes and coenzymes. Perfect for students studying biochemistry or related fields.