Chapter 3 - Biochemistry PDF

Chapter 3 Thursday, September 5, 2024 7:12 PM Learning Outcomes ✔ Why are you learning this?...

Chapter 3 Thursday, September 5, 2024 7:12 PM Learning Outcomes ✔ Why are you learning this? - Drugs are molecules! Recognize how the interactions between a receptor and a ligand that it binds depends on the concentration of the ligand ○ Even protein therapeutics and gene therapy! Describe the key principles for the binding of oxygen by myoglobin and hemoglobin - The proteins, nucleic acids, etc. in our bodies are (macro) Discuss the concept of binding cooperativity and how it applies to hemoglobin, and how cooperativity enhances the ability of molecules! hemoglobin to function as a highly effective oxygen carrier - Drugs produce therapeutic effects by binding to proteins, nucleic acids, etc in our bodies! Section 3.1 Binding is a fundamental Process in Biochemistry - Molecular recognition = the ability of certain molecules to bind to one another amongst infinite random interactions - Structure of the complexes formed have particular three-dimensional shapes (secondary, tertiary, and quaternary) ○ Enables the complexes to have defined properties Receptors and Ligands - A receptor "R" (typically a protein) and a potential binding partner called a ligand "L" can bind together to form complex "RL" - [R] + [L] ⇌ RL (the brackets represent concentration) (concentration dependent effect) - Comparing the percentage of RL with the concentration of added L reveals how tightly R binds to L - 1 R 3 different L's Binding Depends on the Concentrations of Binding Partners Binding of L to R Can be Characterized by L1/2 - L1/2 = the concentration of L at which half of the receptor is - bound - d to the L and half is free - Ligand concentration When measuring potency, the lower the concentration of ligand to achieve L/2, the more potent - This graph shows how well different substances (ligands) stick to a the interaction with its receptor receptor, which can affect how they work - Drug effectiveness if a drug binds tightly to its target receptor (the black line) it can be very effective even at low doses. If it binds weakly (like the blue line), you might need a much higher dose for it to work, or it might not be effective at all. - Low concentration = low dose if a drug has a high affinity for its receptor (strong binding, black line) it can work well at LOW concentration. - High concentration = high dose: if a drug has low affinity for its receptor (weak binding, blue line) you need a higher concentration to achieve the same effect. This means a larger dose is required to get enough of the drug to bind to the receptor and have an effect Proteins Include Binding Pockets That are Complementary to Ligand Shapes Proteins Can Selectively Bind Certain Small Molecules - Estrogens = steroid hormones that play primary roles in the development of the female The estrogen receptor: reproductive system and secondary sex characteristics - Has a narrow binding pocket linked with hydrophobic residues - Estrogen receptor = binds estrogens (important signaling molecule) - Fits neatly around estrogen ligands - Estradiol binds to estrogen receptors with an L1/2 of ~1nM (10^-9 M)