Associations of amphipathic molecules in aqueous solutions.
Ionic Mobilities in H 2 O at 25°C.
Mean lifetime of a hydronium ion is s This makes proton transfer reactions (acid base reactions) among the fastest in aqueous solutions.
Acid Base Chemistry HA + H 2 OH 3 O + + A - Conjugate acid Conjugate base K = [H 3 O + ][A - ] [HA][H 2 O] K = dissociation constant is a measure of the strength of an acid [H 2 O] = 55.5M K a = K[H 2 O] = [H + ][A - ] [HA] [H 3 O + ] = [H + ]
Water as an acid H2OH2OH + + OH - Conjugate acid Conjugate base K = [H + ][OH - ] [H 2 O] Pure water contains equimolar hydroxide ions and protons At 25ºC K w = M 2 [H + ] = [OH - ] = M [H 2 O] = 55.5M K w = K[H 2 O] =[H + ][OH - ]
Henderson Hasselbach and pH -log[H + ] pH = [H + ] =K a ([HA]/A - ]) pH =-log K a + log ([A - ]/[HA]) pH =pK a + log ([A - ]/[HA])
Titration curve of a 1L solution of 1M H 3 PO 4.
Thermodynamics First Law Energy is conserved ∆U = U final - U initial = q - w q = heat absorbed w = work done ∆U = 0 for any process that returns to its initial state Exothermic processes release heat Endothermic processes gain heat
H = U + PV Enthalpy is defined as: P = pressure (constant) ∆V = volume (insignificant) ∆H = ∆U + P∆V ∆H = ∆U = q - w ∆H = q w often is zero in biological systems q = heat transferred to/from the surroundings
Thermodynamics Second Law Entropy increases ∆S universe > 0
Two bulbs of equal volumes connected by a stopcock. N molecules of gas 2 N equally probable ways of distributing them
W L = N! L!(N-L)! W L = number of different ways of placing L of the N molecules in the left bulb For any N the most probable state is L = N/2 (half the gas in the left bulb) Probability = W L /2 N If N = the probability that the # of molecules in the left and right bulbs differ by 1 molecule is 10 billion in
Page 54 9 positions, 4 identical balls W = = 126 (4321)(54321) Only 4 out of 126 possible arrangements have 4 balls touching each other W L = N! L!(N-L)! W L = number of different ways of placing L of the N molecules in the left bulb
S = k B ln W In a system where energy does not change a spontaneous process has ∆S > 0 W L = N! L!(N-L)! W is approximately 10 7x10 22 if the previous experiment uses a mole of real gas To make this more manageable entropy was “invented”
This does not mean that order cannot exist In a localized system. It means that order can only exist at the expense of surrounding systems. Biology gains order by disordering the nutrients that it consumes. ∆S system + ∆S surroundings = ∆S universe > 0
Free Energy G = H - TS ∆G = ∆H - T∆S ∆G ≤ 0 for a spontaneous process
Exergonic∆G < 0Spontaneous Endergonic∆G > 0Must input energy
Variation of Reaction Spontaneity (Sign of ∆G) with the signs of ∆H and ∆S.
How do we drive endergonic processes?
Greek lettering scheme used to identify the atoms in the glutamyl and lysyl R groups.
An -amino acid
Glycine - The Simplest -Amino Acid Fischer Projection Preferred representation
L- -alanine or (-)- -alanine (S)- -alanine S = counterclockwise Alanine CC
-valine L-(-)- -valine S- -valine Valine CC
-leucine L- -leucine (-) - -leucine S- -leucine Leucine CC
Isoleucine 2 chiral centers (2S,3S)-isoleucine
Both centers are S CC CC
Methionine is non-polar but S-atom is reactive -methionine L-methionine (-)- -methionine S-methionine
Methionine is non-polar but S-atom is reactive -methionine L-methionine (-)- -methionine S-methionine CC
Proline is a cyclic imino acid -proline L-proline (-)- -proline S-proline CC
Large non-polar aromatic -phenylalanine L-phenylalanine (-)- -phenylalanine S-phenylalanine
Large and non-polar -phenylalanine L-phenylalanine (-)- -phenylalanine S-phenylalanine CC
Large and non-polar -tryptophan L-tryptophan (-)- -tryptophan S-tryptophan
Large and non-polar -tryptophan L-tryptophan (-)- -tryptophan S-tryptophan CC
Uncharged Polar Amino Acids -tyrosine L-tyrosine (-)- -tyrosine S-tyrosine +
Uncharged Polar Amino Acids -tyrosine L-tyrosine (-)- -tyrosine S-tyrosine CC
Uncharged Polar Amino Acids -serine L-serine (-)- -serine S-serine CC +
Uncharged Polar Amino Acids - cysteine is often charged -cysteine L-cysteine (-)- -cysteine R-cysteine CC +
Uncharged Polar Amino Acids -asparagine L-asparagine (-)- -asparagine S-asparagine CC +
Uncharged Polar Amino Acids -glutamine L-glutamine (-)- -glutamine S-glutamine CC +
Threonine has 2 chiral centers (2S,3R)-threonine
CC CC
Charged amino acids -arginine L-arginine (-)- -arginine S-arginine CC +
Charged amino acids -lysine L-lysine (-)- -lysine S-lysine CC +
Charged amino acids -histidine L-histidine (-)- -histidine S-histidine CC +
Charged amino acids -glutamate L-glutamate (-)- -glutamate S-glutamate CC +
Charged amino acids -aspartate L-aspartate (-)- -aspartate S-aspartate CC +
AlanineAlaA CysteineCysC GlycineGlyG HistidineHisH IsoleucineIleI LeucineLeuL MethionineMetM ProlineProP SerineSerS ThreonineThrT ValineValV ArginineArgR AsparagineAsnN AspartateAspD GlutamateGluE GlutamineGlnQ LysineLysK PhenylalaninePheF TryptophanTrpW TyrosineTyrY
Non-standard encoded amino acids Selenocysteine Sec, U Pyrrolysine Pyl, O + +
Amino acids bear structural similarity to each other Asparate Asparagine Glutamate Glutamine
Amino acids bear structural similarity to each other Cysteine Selenocysteine Serine Threonine
Amino acids bear structural similarity to each other Tyrosine Phenylalanine +
Amino acids bear structural similarity to each other Histidine Asparagine Glutamine Arginine Histidine Arginine
Amino acids bear structural similarity to each other Histidine Tryptophan
Amino acids bear structural similarity to each other Phenylalanine Tyrosine Phenylalanine Leucine
Glutamate, glycine –neurotransmitters D-serine –neurotransmitter S-adenosylmethionine –methyl transfer
Page 77 Non-peptide amino acids
Titration curve of glycine.
These values are the pKa’s of the free amino acids in aqueous solution. As we shall see later an aqueous solution may not represent reality
Hydrophobic pocket