Lecture 2 & 3: Water, pH & buffers

Question 1

Reversible Ionization

Answer 1

Results from nucleophilic attack by oxygen on a proton of an adjacent water molecule
H2O H+ + OH-

Question 2

Keq: Equilibrium Constant

Answer 2

Ratio of [product] to [reactant]; water: ([H+][OH-])/[H2O]
Keq=1 : [product] = [reactant]
      >1: [product] > [reactant]
      <1: [product] < [reactant]
Keq of water: 1.8 x10^-16

Question 3

Kw: Ion product of water

Answer 3

Kw = 1x 10^-14 = [H+][OH-]

If [H+] increases, then [OH-] decreases

Question 4

pH: -log [H+]

Answer 4

Acid: release/donates protons
Base: accept protons

Question 5

Acid-Base Disorders (Pathological)

Answer 5

Metabolic acidosis
Increase production of acid: lactic acidosis (overproduction of lactic acid), ketoacidosis (overproduction of ketone bodies), complications of drugs or other exposures
Loss of bicarbonate: diarrhea, altered kidney function

Question 6

Small Changes in pH as a Signaling Mechanism

Answer 6

pH increase of 0.2 to 0.3 promotes cell proliferation, migration, assembly of actin filaments
High intracellular pH = cancer
Low intracellular pH = several neurodegenerative diseases

Question 7

Strong acid vs. Weak Acid

Answer 7

Strong acid ionizes completely; one way arrow

Weak acid does not ionize completely; equilibrium arrow

Question 8

Ka: A constant for any given acid

Answer 8

HA A- + H+

Ka= [H+][A-] / [HA]
If Ka is large, indicates a strong acid
Small pKa indicates a strong acid

Question 9

Henderson-Hasselbalch Equation: pH & pKa relationship

Answer 9

pH = pKa + log [A-]/[HA]
Applies to weak acids & bases
Bases want to keep their protons

Question 10

Henderson-Hasselbalch

Answer 10

When [HA]=[A-], the acid is 50% dissociated & undissociated; pH=pKa it is the pI (inflection point); point of max buffering capacity

Points on curve: different ratios of dissociated to undissociated weak acid

Question 11

How is pKa useful?

Example: Aspirin

Answer 11

Aspirin is a weak acid with a pKa of 3.5
Absorbed through the cells lining the stomach (pH:1.5) & SI (pH:6)
Absorption requires passage through the pm; rate of absorption determined by the polarity of the molecule: charged and highly polar passes slowly & neutral hydrophobic ones pass rapidly
Aspirin more absorbed in stomach b/c more acidic & H+ in environment

Question 12

Normal vs. Cancer Cells

Answer 12

Normal:
Intracellular pH: ~7.2
Extracellular pH: ~7.4

Cancer:
Intracellular pH: >/= 7.4
Extracellular pH: ~6.7-7.1

Question 13

Selective Advantages for Cancer Cells

Answer 13

Favors:
  Proliferation
  Avoid apoptosis
  Migration and invasion
  Avoid immune detection

Question 14

Consequences of Reverse pH Gradient in Cancer Cells

Example: Doxorubicin

Answer 14

pKa = 8.2; has an ionizable primary amine
Will have a higher percentage of the drug at pH<8.2 in the ionized form
Normal cells will take up a greater percentage of doxorubicin : more acidic in a normal cell than cancer cell (7.2<7.4)

Question 15

How does the body compensate for the generation of acid due to metabolic activity?

Answer 15

Buffers

NOTE: Metabolism results in 13-22 moles of acid produced/day. If dissolved in water, pH would be <1.

Question 16

pH Homestasis

Answer 16

Blood pH must be maintained within a narrow range (7.36-7.44)
Intracellular pH: 7.1 (range 6.9-7.4)

Question 17

Buffers

Answer 17

A mixture of an undissociated acid & its conjugate base (ex. Acetic acid and acetate ion)

Consequence: It causes solution to resist changes in pH when either H+ or OH- is added

Question 18

Buffer Systems of Physiological Importance

Answer 18

Phosphate Buffer: H2PO4- HPO4 2- + H+ (pKa: 7.2)
Intracellular fluid

Carbonic Acid/Bicarbonate: CO2(dissolved) +H2O HCO3- + H+
Carbonic acid/bicarbonate system works b/c of high [CO2] dissolved in body fluids & equilibrium b/w dissolved CO2 & CO2 in lungs

Proteins (amino acids)

Question 19

How Do Buffers Function?

Answer 19

Simple: Combines with H+ or OH- & converts them to non-ionized form

Complex: Involves 2 reversible equilibria; one involving water

Question 20

What Determines Effectiveness of a Buffer?

Answer 20

pKa relative to the pH of the solution

Concentration