Piamsook Pongsawasdi
Somporn Kamolsiripichaiporn
January 2016


Universality of chemical intermediates and transformation
- In 1954, Jacques Monod summarized as
“What is true of
is true of the elephant ”
Example:
- Glucose breakdown in yeast or animal muscle cells involves the same 10 enzymes and 10 intermediates
2



< 30% of ∼ 100 naturally occurring chemical elements are essential to organisms
Most have relatively low atomic number
3

(e.g. H, O, N, C)



Daily requirement - g amount in diet (human, plant, microorganism)
Structural component of cells & tissues
Most abundant: H, O, N, C ( > 99% of the mass of most cells)

- they are the lightest element capable of forming 1,2,3, and 4 bonds, and they form the strongest bonds

(e.g. Fe, Cu, Zn)
Daily requirement – mg amount in diet

Essential to function of specific proteins/enzymes
E.g. O
2 transporting capacity of hemoglobin depends on 4 Fe +2 that make up only 0.3% of its mass
4



70 % of cell weight
Through osmosis, water controls osmotic pressure in cells
Inside
Lower
[H
2
O]
Cell membrane
(semipermeable)
Osmosis
Outside higher
[H
2
O]
Isotonic – [H
2
O] out
= [H
2
O] in hypotonic – [H
2
O] out
> [H
2
O] in
 swollen cells hypertonic – [H
2
O] out
< [H
2
O] in
 shrink cells


Water ionizes and interacts through H-bonding
Water has weak interaction with biomolecules
5

Structure of H
2
O
 O atom – tetrahedral-like structure
 H-bonding between water molecules
 Melting point (0 o C) and boiling point
(100 o C), higher than other solvents
 Polar solvent
H-bonding in ice
In ice , H
2
O has 4 H-bonds with another H
2
O (only 3.4 H-bonds in liquid )  ice has lower density and float in water
6

Pure water is slightly ionized
H
2
O H + + OH -
K eq
= [H + ][OH ]
K eq
= equilibrium constant [H
2
O]
All H + exist as H
3
O +
K w
= K eq
K w
= ion product of H
2
O
[H
2
O] = [H + ][OH ]
At 25 o C [H
2
O] = 55.5 M, K eq
= 1.8 x 10 -16 M
K w
= 1.0 x 10 -14  [H + ] = [OH ] = 10 -7 mol/l
Sőrensen definition for [H + ], pH = -log[H + ] = -log [10 -7 ] = 7
which is pH of pure water
Thus neutral solution, pH = 7; acid solution, pH < 7; base solution, pH > 7
Range of pH solution 0-14
7

HA + H
2
O acid base
H
3
O + + A -
Conjugate acid
Conjugate base
K eq
= [H
3
O + ][A ]
[HA][H
2
O]
K a
H +
=
=
K eq
[H
2
O] = [H
3
O + ][A ] = [H + ][A ]
[HA] [HA]
K a
[HA]
[A ]
log [H + ] = log K a pH = pK a
+ log [HA]
[A ]
+ log [A]
[HA]
Henderson-Hasselbalch equation
8




A solution that can resist change in pH when small amount of H + or OH - is added
Consists of weak acid & conjugate base or weak base & conjugate acid
Example of buffer in biological system
 amino acid/protein (NH
+
3
/ NH
2
, COOH / COO )
 hydrogen phosphate system in all cells, e.g. in ATP (H
2
PO
4
/ HPO
4
2 )
 bicarbonate system in blood (H
2
CO
3
/ HCO
3
)
9

The best buffering capacity is at pH = pK a
When titrate glycine with KOH, two pK a are obtained due to and NH
3
+
10

I. Versatility of C bonding (covalent bond)
- single bonds with H
- single and double bond with O and N
- single, double, and triple bond with C
C accounts for more than half the dry weight of cells
11

II. Geometry of C bonding
•
C atoms have a characteristic tetrahedral arrangement of the
4 single bonds (greatest significance in biology)
•
C-C has a free rotation around each single bond (0.154 nm)
•
C=C, a shorter bond (0.134 nm), rigid, limited rotation, all atoms lie in the same rigid plane
12


Several common functional groups are usually found in a single biomolecule
13


H-atoms in HCs are replaced by variable functional groups families of organic compounds

Covalently linked C atoms
in biomolecule can form linear/branched chains/ cyclic structures
14

A. Covalent bond
- pairing of e in outer orbital of two interacting atoms
- strong, very stable due to high bond energy ( ∼ 100 kcal/mol)
- major bond in small biomolecules e.g. in H
2
O (H-O-H), amino acid - glycine (NH
3
+ -CH
2
-COO )
- links between monomers to form polymers e.g. protein, DNA, polysaccharide
B. Non-covalent bond
- weak interaction ( ∼ 1-5 kcal/mol)
- though weak, but important, many can form within or
between biomolecules, e.g. forming 3D-structure of
protein, double helix of DNA, binding of Ag to Ab, E to S
- 4 main types: H-bond, hydrophobic, ionic, and van de Waals interactions
15

Common H-bonds in biological system
Some biological important H-bonds
Direction of H-bond
16

Polar (hydrophilic) VS Non-polar (hydrophobic)
17

 Lipid, steroid, vitamin, protein are examples of amphipathic molecules
(contain both polar and non-polar part)
 In aqueous solution, hydrophobic part interacts to stabilize structure, while exposes polar part to water
 Hydrophobic interaction
- among lipids, and between lipids and proteins; stabilizes membrane structure
- between non-polar amino acids; stabilizes 3D-structure of protein
Micelle structure of lipid
18

 Interaction between atoms of charged functional groups
Attraction force
Repulsion force
19

 Interaction between any two uncharged atoms in close proximity
 Each atom has van der Waals radius
(closest distance before repulsion)
20

21

Cells Contain a Universal Set of Small Molecules

Universal set of small molecules in cytosol
( primary metabolites , 1 ° MBs)
- central metabolites of the major pathway occurring in nearly every cells, play role in growth, development, and reproduction of the organism, e.g. amino acids, nucleotides, sugars, carboxylic acids
In addition to 1 ° MBs, many plants and fungi also have secondary MBs
(small molecules that are not directly involved in growth, development and reproduction but play specific role (mostly in defense), e.g. morphine in opium poppy, erythromycin from fungi)

Metabolome = the entire collection of small molecules in a cell
22




Many biomolecules are macromolecules (polymers with MW > 5,000, assembled from simple precursors)
Proteins, nucleic acids, and polysaccharides are macromolecules in cells
Proteins are the largest fraction, besides water
23

Macromolecule
Proteins
Nucleic acids
Polysaccharides
Monomer Function amino acids catalysis (enzyme), structure, receptor, transporter nucleotides store & transmit genetic information
(DNA), structure, catalysis (RNA) mono-
saccharides energy-rich fuel stores, structural composition of plant/bacterial cell wall, external recognition elements


Proteins & Nucleic acids are informational macromolecules
Proteins are the most versatile of all biomolecules
Proteome = the sum of all proteins in a cell
* Lipids - not macromolecules, water insoluble, function in structure
(membrane), energy stores, pigments, intracellular signal
24


Covalent bonds, functional groups, and stereochemistry
(the arrangement of the atoms in 3D-space) contribute to the function of a biomolecule

A carbon-containing compound commonly exists as
“ stereoisomers ” (molecules with the same chemical bonds but different configurations)

Interaction between biomolecules are stereospecific , requiring specific configuration in the interacting molecule, e.g. binding between enzyme and substrate
25

(a) Perspective diagram
(b) Ball and Stick model - bond lengths and angles
- better represented
(c) Space-filling model - atom radius, space of molecules
26


Configuration is conferred by the presence of
(a) double bonds , around which there is no freedom of rotation
(b) chiral centers , around which substituent groups are arranged in a specific orientation

Configuration – interconversion between 2 isomers by breaking covalent bond(s) , requires input of energy
27

(trigger electrical change in the retinal cell that lead to a nerve impulse)
28

Chiral molecule Achiral molecule

Chiral - has optical rotation (rotate plane-polarized light)
- equimolar solution of 2 enantiomers = a racemic mixture
29



Enantiomers and diastereoisomers of 2,3- disubstituted butane
Number of stereoisomers = 2 n , where n = number of chiral carbons
30

RS system


The most useful for a compound with > 1 chiral center
Each group attached to a chiral C is assigned a priority
31

DL system - uses glyceraldehyde as reference, commonly used for saccharides
In living organism, chiral molecules are usually present in only one chiral form, e.g. amino acids occur in L isomer, glucose occurs in D isomer
32


The spatial arrangement of substituent groups that, interconversion between isomers occurs without breaking of covalent bonds , but by changing of bond angles
Example: boat and chair conformation of hexose
33

Example: staggered and eclipsed conformation of ethane
34


Biomolecule A + Biomolecule B with correct stereochemistry complementary fit correct function e.g. reactant + enzyme
hormone + receptor
antigen + antibody
Stereospecificity
 Ability to distinguish between stereoisomers
 A property of enzymes and proteins
 Characteristic feature of the molecular logic of living cells
If an enzyme is complementary to L isomer of a compound, it won’t bind to D isomer, as similar to a left glove does not fit a right hand
35





Due to bonding versatility, C can produce various C-C skeletons with an array of functional groups biomolecules with biological and chemical characteristics
Ionization of water and weak acid contributes to buffering capacity in biological system
Covalent and non-covalent interactions are both important in living cells
Living cells have a universal set of small molecules which interconvert via the conserved central metabolic pathway
36





Proteins & nucleic acids are linear polymers of simple monomeric subunits . Their sequences contain the information that gives each molecule its 3D-structure and biological function .
Molecular configuration can be changed by breaking covalent bonds . For a chiral C, arrangement of substituent groups stereoisomers with distinct property. Only one isomer is biological active .
Molecular conformation is the position of atoms in space that can be changed by rotation about single bond , without covalent bond breaking.
Interactions between biomolecules are almost stereospecific .
37