Lecture #03: Properties of Water - pH Flashcards
Use of pKa: Aspirin
One reason the pKa is important can be explained with aspirin. Its affects are generally going to be put in place by its actions in the brain, but you take it in with your mouth and it lands in the stomach. The pH of the stomach is 1-2. Since the pKa is above the pH of the stomach, the proton on it will stay, and aspirin stays as a nonpolar molecule. Nonpolar molecules have a much easier time crossing membranes, so since aspirin is nonpolar, it’ll be able to travel through the stomach lining and then to the brain, due to the fact that the pH of the stomach is lower than aspirin’s pKa.
Getting a Drug Across a Membrane
- So generally, to get a drug across a membrane, you want that particular drug to be uncharged. Small changes to its functional groups to make it so is key.
- In a lipophillic environment, you want an uncharged molecule in order to cross over. If in a soluble environment, you want charged molecule.
Use of pKa: Spectral Properties
• Another way pKa is useful can be explained using spectral properties. Take p-nitrophenol, an artificial substrate. If the pH of the solution it is in rises above its pKa, the molecule is going to dissociate and lose a H+ atom, and in the lab you can tell this when it turns from a clear color to yellow.
Use of pKa: Specific Reactions
• To explain how pKa is useful in specific reactions, take the active site of the digestive enzyme, chymotrypsin, which contains 3 amino acids. When it begins to break down dietary proteins, you have activity between these 3 amino acids. One of the, histidine, accepts a proton from the OH of serine, another AA. Having an amino acid that can function as an acid or a base is the basis of how catalysis can happen, and its ability to do that is based on pKa.
Buffer Composition
• A buffer is a mixture of an undissociated acid and its conjugate base. Like, acetic acid and acetate ion. It causes a solution to resist changes in pH when either H+ or OH- is added.
○ A weak acid is most effective in buffering against pH changes in the vicinity of its pKa value.
Buffer Mechanism
• Simplistically, buffers combine with H+ or OH- and converts them to a non-ionized form. Complicatedly, it involves 2 reversible equilibria, one involving water, other the weak acid and conjugate base. To sum its effects, they basically work together to absorb the H+ and OH-. Water’s reversible ionization makes this possible.
Importance of Understanding Buffers
• We need to understand buffers to understand how an organism controls the pH of its internal environment.
Buffer in Blood
• In aerobic biochemical consumption of fuels, carbon dioxide is produced. It can react with water to form a weak acid, carbonic acid, which can readily dissociate into a proton and bicarbonate ion. This conjugate acid-base pair acts as a buffer for blood pH, binding with H+.
Phosphate Buffer
• A Phosphate buffer is used to keep the pH of intracellular fluids maintained.
What Else Can Be Used As a Buffer?
• Proteins can be used as buffers as well.
Effectiveness of Buffer
• pKa relative to the pH of the solution and concentration are two factors to determine effectiveness of a buffer.
○ To explain pKa’s effect, think of a titration curve. If it is steep at the far left or right sides of it, you are outside of the buffering range. At a pH where it equals pKa, you will have the maximum buffering capacity. pKa determines at what pH the maximum buffering capacity will occur.
○ To explain concentration, the more concentrated the buffer, the more powerful it is. More species to interact with solution to resist pH changes.
Cancer Cells & pH
• Cancer cells use primarily glycolysis for energy because they consume a lot of glucose and it contributes to a reverse pH gradient. Cancer cells have a greater intracellular pH than extracellular, opposite of our bodies. So the production of lactic acid will decrease extracellular pH, which will favor a lot of things cancer cells do. Like proliferation, avoid apoptosis, migration & invasion, avoid immune detection. Immune cells cannot tolerate an acidic environment.
Flu & pH
• Patients with flu have slightly more alkanine pH, due to an increase concentration in bicarbonate ion concentration. Body will attempt to eliminate bicarbonate ion by excretion through the kidney.
