Definition and Biological Significance
Enzymes are biocatalysts produced by living cells, predominantly proteins that accelerate chemical reactions within biological systems with remarkable specificity and efficiency. Some RNA molecules called ribozymes also act as catalysts. Enzymes reduce activation energy, enabling physiological reactions to occur rapidly at body temperature.
They are essential for metabolic pathways, regulating bodily functions such as digestion, energy production, and DNA replication. Dysfunctional enzymes cause metabolic diseases, making them critical in both health and disease. Measurement of enzyme levels in bodily fluids serves as valuable diagnostic tools.
Applications of Enzymes
- As therapeutic agents for enzymatic deficiency diseases.
- In diagnostics, such as glucose oxidase in diabetes testing.
- In drug development targeting enzymes.
- Industrial applications, e.g., detergents with proteases.
- Biosensors for detecting biochemical substances.
Classification and Nomenclature
The International Union of Biochemistry (IUB) categorizes enzymes into six classes:
- Oxidoreductases: Catalyze oxidation-reduction reactions.
- Transferases: Transfer functional groups from one molecule to another.
- Hydrolases: Catalyze hydrolytic cleavage of bonds.
- Lyases: Remove groups to form double bonds or add groups to double bonds.
- Isomerases: Catalyze isomerization changes within a molecule.
- Ligases: Join two molecules at the expense of ATP hydrolysis.
Each enzyme has a systematic name reflecting its substrate and reaction plus an EC number for classification. Due to complexity, trivial names (e.g., lactase, amylase) are commonly used.
Mechanisms of Enzyme Action
Enzymes bind substrates at an active site consisting of catalytic and binding regions. These sites are three-dimensional and shaped to fit substrate molecules precisely.
Models Explaining Specificity
- Lock and Key Model: Enzyme active site is rigid and fits substrate exactly.
- Induced Fit Model: Active site is flexible and molds around substrate during binding.
Key features: Formation of enzyme-substrate complex lowers activation energy; enzyme is regenerated post-reaction.
Factors Affecting Enzyme Activity
Enzyme Concentration Reaction rate increases proportionally with enzyme amount, assuming substrate saturation. Substrate Concentration Initial linear increase in velocity with substrate, saturates at high substrate levels (Michaelis-Menten kinetics). Temperature Optimal around 35-40°C; beyond which denaturation reduces activity. pH Each enzyme functions best within a narrow pH range; extremes denature enzyme or alter charge interactions. Product Concentration Product buildup can inhibit enzyme (feedback inhibition). Activators Metal ions or cofactors essential for activity (e.g., Mg2+, Zn2+). Time and Radiation Prolonged exposure or UV/X-rays can inactivate enzymes.
Enzyme Kinetics
Enzymes exhibit varying kinetics: first order at low substrate and zero order at saturation. The Michaelis constant (Km) quantifies substrate affinity, with lower Km indicating higher affinity. Vmax represents the maximal velocity.
Enzyme Inhibition
- Reversible Inhibition:
- Competitive: Inhibitor competes with substrate for active site; increasing substrate reverses inhibition; Km increases, Vmax unchanged.
- Non-Competitive: Inhibitor binds elsewhere, altering enzyme function; Km unchanged, Vmax decreases.
- Irreversible Inhibition: Inhibitor covalently binds enzyme, permanently inactivating it. Examples include nerve gases and penicillin.
- Allosteric Inhibition: Regulatory molecules bind to sites other than active site, inducing conformational changes that alter activity.
Therapeutic Enzyme Inhibitors
Many drugs work by inhibiting enzymes:
- Statins inhibit HMG-CoA reductase to lower cholesterol.
- ACE inhibitors like captopril for hypertension.
- Antiviral drugs targeting reverse transcriptase.
Isoenzymes
Isoenzymes catalyze the same reaction but differ structurally and functionally. Examples include:
- Lactate dehydrogenase (LDH) isoenzymes differing in tissue distribution and kinetics.
- Creatine kinase isoenzymes as markers for myocardial infarction.
- Various alkaline phosphatase isoenzymes with diagnostic value in liver and bone diseases.
- Alcohol dehydrogenase isoenzymes differing between ethnic groups affecting alcohol metabolism.
Coenzymes
Coenzymes are reusable organic molecules, mostly vitamin derivatives, that assist enzymes by carrying electrons, atoms or functional groups during reactions. They are part of holoenzymes with apoenzyme protein components. Coenzymes include NAD+, FAD, coenzyme A, and pyridoxal phosphate.
Coenzymes act as transient carriers cycling between oxidized and reduced forms, enabling continuous catalysis.
Understanding enzyme structure, mechanisms, and regulation equips pharmacists with knowledge essential to drug action, disease diagnosis, and therapeutic intervention.
Detailed Notes:
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