Enzyme Kinetics: Michaelis-Menten Equation

Enzyme Kinetics

• The Michaelis-Menten equation describes the relationship between substrate concentration and reaction rate.
• Key features of the Michaelis-Menten equation include:
  • Rate approaching Vmax
  • KM indicating substrate concentration at half Vmax
  • Rate being proportional to substrate concentration
• Enzyme kinetics is the study of the rates at which enzyme reactions occur, including the formation of products.
• The rate of reaction is the formation or disappearance of substrate, which occurs in the forward and reverse.
• Enzyme rate decreases over time due to substrate depletion and product accumulation.
• Enzymes are catalysts and are not consumed in the reaction.

Michaelis-Menten Constant (KM)

• KM is a measure of affinity and indicates how strongly the substrate binds to the enzyme.
• Low KM indicates tight binding, while high KM indicates weak binding.
• Physiological relevance of KM is demonstrated in the sensitivity of some individuals to alcohol, where individuals with a point mutation have an aldehyde dehydrogenase with an increased KM.

Enzyme Inhibition

• Enzyme inhibition can occur through reversible and irreversible inhibitors.
• Reversible inhibitors include:
  • Competitive inhibitors (bind to the active site, competing with the substrate)
  • Non-competitive inhibitors (bind to an allosteric site, rendering the enzyme catalytically inactive)
  • Uncompetitive inhibitors (bind to the enzyme-substrate complex, distorting the active site and preventing product formation)
  • Mixed inhibitors (bind to the allosteric site, resembling non-competitive inhibition but with greater affinity for either the free enzyme or the enzyme-substrate complex)
• Irreversible inhibitors include:
  • Group-specific inhibitors
  • Reactive substrate analogs
  • Mechanism-based inhibitors

G-Protein Diversity and Signal Transduction Specificity

• G-proteins are characterized by their alpha-subunits, which are grouped into different families.
• Each family has specific functions and mediates different actions.
• Receptor and G-protein specificity determines the signaling process.
• G-proteins can activate or inhibit various components, such as adenylate cyclase, phospholipase C, and protein kinase A.

Neurotransmitter Receptors

• Neurotransmitters can bind to both ionotropic and metabotropic receptors.
• Specific examples of neurotransmitter receptors include:
  • Acetylcholine (nicotinic and muscarinic receptors)
  • Glutamate receptors
  • Dopamine receptors
• The dopamine signaling pathway is linked to conditions such as psychosis and hallucinations, and is a target of antipsychotics.

Hormonal Signaling

• Hormonal signaling can be classified into two types:
  • Water-soluble hormones (act on cell surface receptors)
  • Lipid-soluble hormones (activate intracellular receptors)
• Lipid-soluble hormones are synthesized de novo in response to a stimulus and are released by simple diffusion.
• Lipid-soluble hormones are reversibly attached to carrier proteins in the blood, which prevents them from having biological activity.
• Free hormone enters the cell by diffusion and binds to intracellular receptors in the cytoplasm or nucleus, affecting gene transcription.

Transport of Large Molecules, Particles, and Fluids Across the Plasma Membrane

• Exocytosis is the process of releasing polar or charged molecules into the extracellular environment.
• Endocytosis is the process of taking in large polar or charged molecules and particles.
• Exocytosis and endocytosis are linked events that help maintain plasma membrane integrity.
• Mechanisms of endocytosis include:
  • Phagocytosis (involves cells ingesting large objects, bacteria, or viruses)
  • Pinocytosis (absorption of extracellular fluids)
  • Receptor-mediated endocytosis (clathrin-mediated and clathrin-independent)
  • Caveolin-mediated and caveolin-independent endocytosis