1. CHEMICAL FOUNDATIONS 2310310 Foundations of Biochemistry
Piamsook Pongsawasdi
Kanoktip Packdibamrung
August 2016

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

3. Elements Essential to Animal Life and Health
 30% of  100 naturally occurring chemical elements are essential to organisms
Most have relatively low atomic number
Periodic table, only a part is shown.
Chemical elements organized based on proporties, increasing atomic numbers
Bulk elements are structural components of cells and tissues, required in the diet in g quantity daily
Trace elements in mg; similar requirements in plants and microorganisms but acquire in different way. 3

4. Elements Bulk elements (e.g. H, O, N, C)
Daily requirement - g amount in diet (human, plant, micro-org)
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
Daily requirement – mg amount in diet
Essential to function of specific proteins/enzymes
e.g. O2 transporting capacity of hemoglobin depends on 4 Fe+2 that make up only 0.3% of its mass
Trace elements (e.g. Fe, Cu, Zn) 4

5. Water is Important for Cells
70 % of cell weight
Through osmosis, water controls osmotic pressure in cells
Water ionizes and interacts through H-bonding
Water has weak interaction with biomolecules
Inside
Outside
Lower [H2O]
higher [H2O]
Cell membrane
(semipermeable)
Osmosis
Isotonic – [H2O]out = [H2O]in
hypotonic – [H2O]out > [H2O]in swollen cells
hypertonic – [H2O]out < [H2O]in shrink cells

6. Structure of H2O H-bonding in ice
O atom – tetrahedral-like structure
H-bonding between water molecules
Melting point (0oC) and boiling point (100oC), higher than other solvents
Polar solvent
H-bonding in ice
In ice, H2O has 4 H-bonds with another H2O (only 3.4 H-bonds in liquid)  ice has lower density and float in water

7. Pure water is slightly ionized
Ionization of Water
Pure water is slightly ionized
H2O H+ + OH-
Keq = [H+][OH-]
[H2O]
Kw = Keq[H2O] = [H+][OH-]
Kw = x  [H+] = [OH-] = 10-7 mol/l
All H+ exist as H3O+
Keq = equilibrium constant
At 25oC [H2O] = 55.5 M, Keq = 1.8 x M
Kw = ion product of H2O
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

8. Ionization of Weak Acid in Water
HA + H2O
acid
base
H3O A-
Conjugate acid
Conjugate base
Keq = [H3O+][A-]
[HA][H2O]
Ka = Keq [H2O] = [H3O+][A-] = [H+][A-]
[HA]
H+ = Ka [HA]
[A-]
log [H+] = log Ka + log [HA]
[A-]
pH = pKa + log [A]
[HA]
Henderson-Hasselbalch equation

9. Buffer
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 (NH3 / NH2 , COOH / COO-)
hydrogen phosphate system in all cells, e.g. in ATP (H2PO4- / HPO4-2)
bicarbonate system in blood (H2CO3 / HCO3-) +

10. The best buffering capacity is at pH = pKa
When titrate glycine with KOH, two pKa are obtained due to ionization of COO and NH3 - +

11. C accounts for more than half the dry weight of cells
Biomolecules are Compounds of Carbon with a Variety of Functional Groups
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 11
C accounts for more than half the dry weight of cells

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

13. Many Biomolecules Contain Polyfunctional Groups
Several common functional groups are usually found in a single biomolecule
Switch with 14 last year 13

14. Most Biomolecules are Derivatives of Hydrocarbons (HCs)
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

15. Bonding and Interactions in Living Cells
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 H2O (H-O-H), amino acid - glycine (NH +-CH2-COO-)
- links between monomers to form polymers e.g. protein, DNA, polysaccharide
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 3

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

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

18. Hydrophobic Interaction
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

19. Ionic Interaction
Interaction between atoms of charged functional groups
Attraction force
Repulsion force

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

21. Non-covalent Interactions in Protein

22. 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

23. - Macromolecules - Major Constituents of Cells
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

24. Macromolecule
Monomer
Function
Proteins
amino acids
catalysis (enzyme), structure, receptor, transporter
Nucleic acids
nucleotides
store & transmit genetic information (DNA), structure, catalysis (RNA)
Polysaccharides
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
Transporter – carry specific molecules into and out of cells
Polysac: extracellular recognition elements that bind to proteins on other cell
Lipid - hydrocarbon derivatives MW
Protein million, NA up to several billions, polysac in millions
informational macromolecules – information rich subunit sequences,
Some oligosac serve as informational molecules
* Lipids - not macromolecules, water insoluble, function in structure (membrane), energy stores, pigments, intracellular signal 24

25. 3-Dimensional Structure is Described by Configuration and Conformation
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

26. 3 Ways to Illustrate Stereochemistry
Alanine in the ionic form at neutral pH
(a) Solid wedge – project out of plane to the reader, dashed wedge = bond extending behind the plane
(a) Perspective diagram
(b) Ball and Stick model - bond lengths and angles better represented
(c) Space-filling model - atom radius, space of molecules 26

27. Configuration 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
Geometric isomers – cis (on same side)/trans (on opposite side) isomers 27

28. Vertebrate retina: Initial event in light detection is the absorption of visible light by the 11 cis retinal. Energy of the absorbed light convert cis to trans
(trigger electrical change in the retinal cell that lead to a nerve impulse) 28

29. Chiral vs Achiral Molecule
Chiral carbon – c atom that links to four different atoms มีความไวต่อการบิดระนาบแสงโพลาไรซ์
คู่ Enantiomers – mirror images
Chiral molecule
Achiral molecule
Chiral - has optical rotation (rotate plane-polarized light)
- equimolar solution of 2 enantiomers = a racemic mixture 29

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

31. Nomenclature of Stereoisomers
RS system
The most useful for a compound with  1 chiral center
Each group attached to a chiral C is assigned a priority
Sinister = left R=RIGHT
เอาตัวที่มี least priority ไว้หลัง แล้วดูทิศทาง 1-2-3 31

32. DL system - uses glyceraldehyde as reference, commonly used for saccharides
L-glyceraldehyde = S-glyceraldehyde
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

33. Example: boat and chair conformation of hexose
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

34. Conformation (continued)
Example: staggered and eclipsed conformation of ethane
Eclipsed = rotation 0 and 120 degree, potential energy rises to maximum
Staggered = 60, 180 degree, fall to minimum
Energy differences small enough to allow rapid interconversion, they cannot be separated 34

35. Interactions between Biomolecules are Stereospecific
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

36. Summary of Chemical Foundations
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
From last year 36

37. Summary (continued)
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.
From last year 37