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Medical Biochemistry pH
Medical Biochemistry
pH
Objectives of pH Lectures encompass three areas of Biochemistry
1 Details of Chemical/Equilibrium: Foundation of pH Balance & Regulation – Understanding of pH = -log[H+] – Know the Behavior of Weak Acids and Bases
• Proton donors & acceptors
– Be able to use the Henderson-Hasselbach Eq. • pH = pK + log(conjugate base/conjugate acid)
– Role of Buffers in pH Balance & Regulation
Objectives of pH Lectures encompass three areas of Biochemistry
2 Role of pH in Macromolecular Structure and Enzyme Mechanism & Regulation – Relationship between Amino Acid Side Chain,
Structure & Catalytic Groups – Role of pH in Protein Structure and Catalytic
Mechanism – Acid-Base Catalysis – H+ donor - acceptor – Regulation of Hemoglobin
• Bohr Effect (T → R) • O2 Transport (linkage to CO2 transport)
Objectives of pH Lectures encompass three areas of Biochemistry
3 Role of pH in Physiology & Pharmacology
– pH Balance in Respiration control - Lung Function • O2 and CO2 transport
– Metabolic control - Kidney Function • HCO3
-, H2CO3, H2PO4-, Na+, K+, NH4
+
– Mitochondria & ATP synthesis – Transport and Effectiveness of Drugs (M2’s)
• DH ↔ D- + H+
Water • 70% of your Body • Net Dipole • tetrahedral electronic structure • H-bonds between 4 nearest neighbors • good solvent properties
– high boiling point, heat of vaporization – hydrophobic effect
Solvent Properties of Water • Polar molecules readily disperse in H2O • Salts dissolve in a shell of H2O dipoles • Amphipathic molecules contain polar &
nonpolar groups • Hydrophobics do not disperse & form micelles • Electrolytes dissociate into anions & cations
– NaCl, KCl, strong acids & bases HCl, NaOH • Weak Electrolytes partially dissociate • Nonelectrolytes dissolve but do not dissociate -
eg. sugars & alcohols
ACID + BASE <-> Conjugate ACID + Conjugate BASE HA + H2O <-> H3O+ + A- HCl + H2O <-> H3O+ + Cl- H2O + H2O <-> H3O+ + OH- ELECTROLYTES
Water is a Weak Electrolyte HOH <=> H+ + OH-
Keq = 1.8 x 10-16 = [H+] [OH-] / [H2O]
Keq x [H2O] = [H+] [OH-] = Kw Keq x 55.5 M = 1.0 x 10-14 = Kw pKw = -logKw = 14
Weak Electrolytes Partially Dissociate
• eg: Lactic acid
• CH3-CHOH-COOH <=> CH3-CHOH-COO- + H+
Keq = [H+] [A-] / [HA] [ ] = moles/liter
Do problem: 0.1 M HA if Keq = 1.38 x 10-4
Water is a Weak Electrolyte pH = log 1 / [H+] = -log [H+] in pure water [H+] = [OH-] thus [H+] = [OH-] = 1.0 x 10-7
or
pH = pOH = 7.0
pKw = pH + pOH = 14
Kw = [H+] [OH-] = constant = 1.0 x 10-14 pKw = pH + pOH = constant = 14
(40 nM)
Weak Acids & Bases • Acid is a proton donor • Base is a proton acceptor • Weak acids dissociate into a conjugate acid-
conjugate base pair (pK = -logK) – eg. Lactic acid <=> Lactate- + H+
– H3PO4 is an acid (H3PO4 <=> H2PO4- + H+)
– PO4-3 is a base (PO4
-3 + H+ <=> HPO4-2
) – H2PO4
- is an acid or a base • (H2PO4
- + H+ <=> H3PO4) • (H2PO4
- <=> HPO4
-2 + H+)
Henderson-Hasselbalch Equation Conjugate acid <=> Conjugate base + H+
Keq = [H+] [base] / [acid]
{1/[H+]} = {1/ Keq} x [base] / [acid]
log{1 / [H+]} = log{1/ Keq} + log [base] / [acid]
pH = pK + log [base] / [acid]
Why is this the buffering region? pH = 3.8? pH = 5.8?
D Fig 1.7
D Fig 1.6 pH = pK + log(B/A)
D Fig 1.8
Amino acids are zwitterions with multiple groups that can lose protons and act as buffers.
BICARBONATE and CO2 NaHCO3 (s) <-> Na+ (aq) + HCO3 - (aq) H+ + HCO3 - <-> H2O + CO2 Acid Base Buffering Soda If carbonate ion is present in blood and there is a source of H+ added it will be buffered and form H2O + CO2
BUFFERS The solution contains a weak acid HA and its conjugate base A-. The buffer resists changes in pH by reacting with any added H+ or OH- so that these ions do not accumulate. Any added H+ reacts with the base A-. H+(aq) + A-(aq) -> HA(aq) Any added OH- reacts with the weak acid HA. OH-(aq) + HA(aq) -> H2O(l) + A-(aq)
! At pH 7.4 how much DH (10 mM, pK 6) is uncharged if DH ↔ D- + H+ ?
• Assignment: Do Quiz 1 on blackboard !
• M1’s use BICH 610 Biochemistry section 1 2012-2013 FALL
• G1’s use Graduate Biochemistry (BCH 710)
