Study Notes on Enzymes and Energy

Chapter 4: Enzymes and Energy

Introduction to Enzymes

  • Enzymes: A class of proteins that function as biological catalysts.

  • Functions and Characteristics of Enzymes:

    1. Increase Reaction Rate: Enzymes accelerate reactions by lowering the activation energy needed.

    2. Do Not Change Reaction Nature: Reactions could occur without enzymes, but slower.

    3. Unchanged Structure: Enzymes remain unchanged after a reaction and can be reused.

Activation Energy

  • Definition: The minimum energy needed for reactants to engage in a chemical reaction.

  • Molecule Behavior: Most molecules do not possess sufficient activation energy for reactions to occur.

    • Heat Addition: Increasing temperature raises the likelihood of reaction occurrence, thus speeding up reactions.

    • Cellular Effects: Heat can have damaging effects on cellular structures; hence, catalysts are critical for lowering reaction temperatures.

Activation Energy Diagram

  • Key Points:

    • The diagram compares reactions with and without a catalyst, illustrating differences in activation energy requirements:

    • Uncatalyzed Reaction Pathway has higher activation energy.

    • Catalyzed Reaction Pathway requires lower activation energy.

Naming Enzymes

  • Historical Naming: First enzymes were given arbitrary names, but an international committee standardized naming.

    • Suffix –ase: All enzyme names end with -ase.(protein is an enzyme)

    • They also decided to make the first part of the name apple to the function of the enzymes

    • Functional Naming:

    • Phosphatases: Remove phosphate groups.

    • Synthetases/Synthases: Catalyze dehydration synthesis.

    • Hydrolases: Facilitate hydrolysis.

    • Dehydrogenases: Remove hydrogen atoms.

    • Kinases: Add phosphate groups.

    • Isomerases: Rearrange atoms in a molecule.

Isoenzymes

  • Definition: Different forms of an enzyme that catalyze the same reaction but may vary slightly in structure (particularly outside the active site).

    • Because names are given to enzymes based on function an enzymes that does the same job in 2 difffrent organs has slight variations to their names

    • However the molecules may be slightly different in areas outside the active site and are called isoenzymes: useful for detecting and diagnosing certain diseases

    • Used to help diagnose certain conditions in the body

  • Clinical Relevance: Useful for disease detection/diagnosis.

    • Example: Creatinine phosphokinase (CK) has three forms: MM (skeletal muscle), BB (brain), and MB (cardiac muscle).

Diagnostic Value of Measuring Enzymes in Blood

  • Table 4.1: Examples of diagnostic values of common plasma enzymes and associated diseases:

    • Alkaline phosphatase: Obstructive jaundice, Paget's disease, bone carcinoma.

    • Acid phosphatase: Prostate cancer, benign hypertrophy of the prostate.

    • Amylase: Pancreatitis, perforated peptic ulcer.

    • Aldolase: Muscular dystrophy.

    • Creatine kinase (CK): Muscular dystrophy, myocardial infarction.

    • Lactate dehydrogenase (LDH): Myocardial infarction, liver disease, renal disease, pernicious anemia.

    • Transaminases (AST and ALT): Myocardial infarction, hepatitis, muscular dystrophy.

Mechanisms of Enzyme Activity

  • Structure-Function Relationship: The specific function of each enzyme is determined by its unique structure.

    • How the interacts with each other is on the active site either through a direct fit (lock and key model)

  • 3D Conformation: Enzymes have a characteristic three-dimensional shape that includes active sites where substrates bind.

  • Substrate Interaction:

    • Lock-and-Key Model: Substrates fit exactly into the active site of the enzyme.

    • Induced-Fit Model: Initial fit may not be perfect; the enzyme adjusts to fit the substrate as it binds.

    • When a substrate binds to the active site of an enzyme it forms temporary bonds weakening the original bond of the substrate and allowing them to break easily

Enzyme-Substrate Binding

  • Complex Formation: When a substrate binds to an enzyme's active site, it forms temporary bonds that stress the substrate's bonds, aiding in the reaction.

  • Illustration:

    • Diagram showing:

    • A + B (Reactants)

    • → C + D (Products)

    • Enzyme remains unchanged.

Measurement of Enzyme Activity

  • Determination: Enzyme activity is assessed by the rate of substrate conversion to product. Influencing factors include:

    1. Temperature: if the temperature is too cold or hot they may not work sufficiently

    2. pH: if it diverted from the pH range it will not work effectively

    3. Concentration of coenzymes and cofactors: inorganic compounds to interact and help enzymes carry out functions

    4. Concentration of enzymes and substrates:increase the amount of substraight you also increase the output

    5. Inhibitory/stimulatory effects of products on enzyme function.

Effects of Temperature on Enzyme Activity

  • Temperature Increases: Reaction rate increases until a few degrees above body temperature (approx. 37°C).

  • Denaturation: Beyond this point, enzymes lose their tertiary structure and become nonfunctional.

    • Graph: Illustrates enzyme activity, peaking around body temperature before dropping as denaturation occurs. If

Effects of pH on Enzyme Activity

  • pH Optimum: Enzymes operate best at a specific pH that correlates with their functional environment.

    • Will work in a very narrow range

    • Changes in pH outside of the functional range will result in irreversible conformational a changes in structure of enzyme which render the enzyme which render the enzyme non functions

  • Irreversible Changes: pH levels outside this optimal range lead to structural modifications causing denaturation.

    • Example Enzymes: Trypsin, salivary amylase, and pepsin exhibit various optimal pH levels.

Coenzymes and Cofactors

  • General Role: Many enzymes require supplementary small molecules for optimal functioning.

  • Coenzymes: Organic molecules typically derived from water-soluble vitamins.

    • Examples:

    • Nicotinamide adenine dinucleotide (NAD+): Derived from vitamin B3 (niacin).

    • Flavin adenine dinucleotide (FAD): Derived from vitamin B2 (riboflavin).

    • Coenzyme A: Derived from vitamin B5 (pantothenic acid).

  • Cofactors: Inorganic molecules such as Ca²⁺, Mg²⁺, Mn²⁺, Cu²⁺, Zn²⁺ that assist enzyme activity

  • Function: Coenzymes and cofactors facilitate the formation of active sites on enzymes by inducing conformational changes for effective substrate binding.

Enzyme Activation

  • Zymogens: Many digestive enzymes are secreted as inactive precursors (zymogens), becoming active post-secretion.

    • Example: Pepsinogen → Pepsin.

  • Phosphorylation/Dephosphorylation: Activation often involves adding a phosphate group (phosphorylation) (turn on), while inactivation involves removing it (dephosphorylation).(turn off)

  • Enzyme Control: Enzyme activity may also be regulated through degradation via lysosomes.

Enzymatic Activities

  • Substrate Concentration: Increases in substrate concentration lead to increased reaction rates until enzyme saturation occurs. The products are

  • Saturation: When all active sites are occupied, adding more substrate will not further enhance the reaction rate.

Reversible Reactions

  • Definition: Some chemical reactions can progress in both forward and reverse directions, influenced by substrate/product concentration.

  • Law of Mass Action: Indicates that as the concentration of a product increases, the reaction will reverse to produce more reactants (example given: H₂O + CO₂ H₂CO₃ H⁺ + HCO₃⁻ facilitated by carbonic anhydrase).

  • When one side gets higher the reaction reverse this is called the law of mass action

Metabolic Pathways

  • Definition: Most biochemical reactions are interconnected, forming metabolic pathways from initial substrates to final products.

    • Most reactions are linked together in a chain (or web) called a metabolic pathway

    • These begin with an initial substrate and end with a final product

    • Every step of the reaction requires a specific enzyme

      • Enzyme Requirement: Each step within a pathway requires a specific enzyme.

Branched Metabolic Pathways

  • Nature of Pathways: Few pathways are linear; most have branches producing several end products from a common substrate.

    • Few metabolic pathways are linear

    • Most include branches where several products can be produced

End Product Inhibition

  • Mechanism: End-products can inhibit the pathway's branch point enzyme if they accumulate, exerting negative feedback to regulate metabolic pathways.

    • Branch points are often inhabiilited by a form of negative feedback in which one of the final products inhibits the branch point enzymes

    • Designed where the final step is the inhibitor

      • Methods of Inhibition:

      1. Competitive Inhibition: The end product competes with substrates for binding at the active site.

      2. Non-competitive or Allosteric Inhibition: The end product binds at a site away from the active site, inducing a conformational change that disables substrate binding.

    • Competitive inhibitor vs nonsompetive inhibitor (allosteric site)


Inborn Errors of Metabolism

  • Definition: Mutations in genes coding for enzymes result in enzymes that are either non-functional or with altered functions, leading to metabolic issues.

    • Occur when there is mutation in a single gene that codes for an enzyme in a metabolic pathway These begin

    • This results in an enzyme that has a new function or one that is nonfunctional

    • Products to be formed after this enzyme in the. Chain are not formed

    • Diseases occur due to loss of end products or accumulation of intermediate products those before the bad enzyme or alternative products

  • Consequences: May result in an accumulation of intermediate metabolites or a deficiency of end-products, causing diseases.

Examples of Inborn Errors of Metabolism

  • Table 4.4: Lists diseases related to amino acid, carbohydrate, and lipid metabolism, addressing clinical results.

    • Diseases:

    • Phenylketonuria (PKU): Accumulation of phenylpyruvic acid, causing mental retardation.

    • Albinism: Lack of melanin, increasing skin cancer risk.

    • Maple-syrup disease: Increased leucine, isoleucine, and valine; can lead to severe brain degeneration.

    • Homocystinuria: Accumulation of homocystine, leading to mental retardation.

    • Lactose intolerance: Inability to utilize lactose contributing to diarrhea.

    • Gierke's disease: Glycogen accumulation in the liver, causing hypoglycemia.

    • Tay-Sachs disease: Glycolipid accumulation, leading to brain degeneration.

    • Hypercholesterolemia: Increased blood cholesterol leading to atherosclerosis.

Bioenergetics

  • Definition: The study of energy flow in biological systems.

Laws of Thermodynamics

  1. First Law of Thermodynamics: Energy cannot be created or destroyed, only transformed; this energy transformation is not 100% efficient.

    • Example: Photosynthesis converts light energy into glucose

  2. Second Law of Thermodynamics: Energy transformations result in a loss of usable energy as heat, reducing available free energy (energy capable of doing work), increasing entropy (disorder).

    • Entropy: Degree of disorder increases with each energy transformation. (In the form oh heat)

    • Relation to Reactions: Connects to definitions of endergonic (requiring energy input) and exergonic (releasing energy) reactions.

Endergonic and Exergonic Reactions

  • Endergonic Reactions:

    • Require energy input, resulting in products with more free energy than reactants.

    • Characterized by increased order (lower entropy in products).

    • Example: Photosynthesis where energy from light converts CO₂ and H₂O into glucose.

  • Exergonic Reactions: more explosive and produces heat as a byproduct

    • Release energy, leading to products with less free energy than reactants.

    • Example: The breakdown of glucose into CO₂ and H₂O provides energy for ATP production.

Energy Obtained from Glucose

  • Total Energy Calculation and Representation: Breakdown of glucose releases energy, represented in biochemical equations.

Calories

  • Definition: A measurement of energy which quantifies the heat required to raise the temperature of 1 cubic centimeter of water by 1°C.

    • Nutrition: Mention of kilocalories (1,000 calories) termed as Calories (capital C) in food.

Coupled Reactions

  • Principle: Energy from food (exergonic reactions) drives endergonic reactions in the body by forming ATP as an energy carrier.

    • Used to drive another process

    • Exergonic reaction to drive th endergonic reactions in our body

      • ATP Formation: ATP production is an endergonic process typically coupled with an exergonic reaction, emphasizing its role as a universal energy carrier.

      • The ATP molecule stores energy in its bonds to be used elsewhere ATP is called the universal energy carrier

  • Mechanism of Coupled Reactions: Diagram illustrated how coupling occurs between endergonic and exergonic reactions, showcasing fluid energy transfer.

  • Exergonic reaction drives endergonic reactions

  • Everything requires energy

Coupled Reactions in ATP Formation

  • Diagram Explanation: Provides a straightforward depiction of ATP synthesis from ADP and inorganic phosphate (Pi).

Coupled Reactions: Oxidation-Reduction

  1. Reduction: Process in which an atom or compound gains electrons, reducing its charge.

    • Reduction reaction: when an atom or compound gains or accepts electrons (it becomes reduced)

  2. Oxidation: Process of losing electrons from an atom or compound, increasing its charge.

    • When an atoms compound loses or donates an electrons

    • These reactions are always coupled for one molecule to lose an electrons These it has to give it to another molecule

      • The molecule that donates the electrons acts as the reducing agent

      • The molecule that accepts the electrons acts as a n oxidizing agent

  3. Coupling of Reactions: Reducing agents donate electrons to oxidizing agents, perpetuating a continuous cycle.

Electron (Hydrogen) Carriers

  • Key Examples:

    • NAD+: Derived from vitamin B3, assists hydrogen transfer, reduces to NADH + H⁺. Oxidized state NAD+, and NADH+ is reduced

    • FAD: From vitamin B2, reduces to FADH₂ after accepting electrons and hydrogen FAD oxidized state FADH reduced state

    • MWCO is the same thing as this is the permeability of that method

    • If the MWCO is too small

    • When you place sodium chloride into a solution sodium chloride is able to defuse across the membrane

    • Bc the sodium chloride is one of the primary ionic compounds

    • Anytime we put an ionic compound it will dissociate th never go back together

    • To change the rate of diffusion you simply change the permutioaton of that solute

    • If you put one type of solute with passive transport we have simple diffusion, osmosis the enzymatic

    • Snare protien

Conclusion

  • Summary: The chapter on enzymes and energy emphasizes their crucial roles in facilitating biochemical reactions, understanding metabolic pathways, and the significance of energy transformations governed by thermodynamic principles.

  • Implications: Comprehension of these biological principles is vital for fields ranging from biochemistry to medical diagnostics, as illustrated through enzyme functionality, metabolic diseases, and energy dynamics in cells.