Chem 114A: Biochemical

Structure and Function

Nav Toor
 Biochemistry
The objective of this course is to introduce the student to the
basic principles of biochemistry. Emphasis is placed on the
fundamental properties of nucleic acids, proteins,
carbohydrates, and lipids.
 Class Website
All lectures will be posted on https://canvas.ucsd.edu/ Students
are responsible for downloading course documents from the
webpage. These documents include homework assignments,
special notes, etc. Check the webpage often: all
announcements will be posted there.
 Chem 114A Course Grade
Midterm #1 – 25%
Midterm #2 – 25%
Final Exam – 40%
Discussion Participation – 10%
 Textbook
Biochemistry by Stryer and Berg

You should be able to study only from the notes.

• Review lecture notes
after class

• Only takes 15 minutes

Use tools to memorize

Histidine?
Scientific Method
 Application of the Scientific
Method to Current Questions

A. Does carbon dioxide increase global

temperatures? YES

B. Does genetically modified (GMO) food

cause human disease or illness? NO
Peer Review Essential to Scientific
Method

• Other scientists evaluate papers before

acceptance for publication in a journal

• Others in the field attempt to independently

replicate the published results to determine
validity
 Journal Quality
• Journals can be judged by impact factor

• Impact factor is the average number of

times a typical article in a journal is cited in
the literature

• Two top general science journals: Science

and Nature
 PhD in Biochemistry
• You get paid to do a PhD - $40 to 50k/year

• Do not pay any tuition

• Do research on a new problem for 5 to 6

years

• Very little course work

• Lots of jobs in the biotech industry with

current starting pay ~$100,000/year
 How to get into a PhD program
• Most important to get research experience
during undergrad

• Letter from research advisor

• Grades are secondary to research

experience; should be at least 3 to 3.3
 Biochemistry
Biochemistry has become the foundation for
understanding all biological processes.

It has provided explanations for the causes of many

diseases in humans, animals and plants

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 Principles of Biochemistry
• Cells (basic structural units of living organisms) are highly
organized and constant source of energy is required to maintain
the ordered state.

• Living processes contain thousands of chemical pathways.

Precise regulation and integration of these pathways are
required to maintain life

• Certain important pathways e.g. Glycolysis is found in almost all

organisms.

• All organisms use the same type of molecules: carbohydrates,

proteins, lipids & nucleic acids.

• Instructions for growth, reproduction and developments for

each organism is encoded in their DNA

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Three Major Phylogenetic Groups
Evolutionary Timeline
 Cells
• Basic building blocks of life
• Smallest living unit of an organism
• Grow, reproduce, use energy, adapt, respond to their
environment
• Many cannot be seen with the naked eye
• A cell may be an entire organism or it may be one of billions of
cells that make up the organism

• Two Basic Types of Cells

• Eukaryotes • Prokaryotes 18
 Elements of Life

Most abundant, essential for all organisms: C, N, O, P, S, H

Less abundant, essential for all organisms : Na, Mg, K, Ca, Cl
Trace levels, essential for all organism: Mn, Fe, Co, Cu, Zn
Trace levels, essential for some organisms: V, Cr, Mo, B, Al, Ga, Sn, Si,
As, Se, I,
 Four Types of Noncovalent Interactions
(Reversible Molecular Interactions)

• Electrostatic interactions

• Hydrogen Bonding

• Van der Waals bonds

• Hydrophobic interactions
 Electrostatic Interactions

• Based on electrostatic attraction, also called ionic

bond

• eg. Positive-negative charge interaction, salt

linkage, salt bridge, ion pair

• Electrostatic interactions is the strongest

noncovalent interaction

• Electrostatic bond energy ranges from 40 to 200

kJ/mol
 Hydrogen Bonds
• A hydrogen bond is the attractive interaction between a
hydrogen atom and an electronegative atom, such as nitrogen,
oxygen or fluorine

• Hydrogen donor: atom to which H is more tightly associated;

eg. O-H, N-H
• Hydrogen acceptor: atom to which H is less tightly associated;
eg. O or N
• The acceptor has partial negative charge that attracts H atom
 Hydrogen Bonds (cont.)
• Distance between two
electronegative atoms involved in
hydrogen bond is 0.3 nm or 3
angstroms

• Remember that 0.1 nm = 1 angstrom

• Hydrogen bond energy ranges from 2

to 20 kJ/mol

• Figure A: Hydrogen bonding

between A-H and B

• Figure B: Some biologically

important H-bonds
 Van der Waals Bonds
• Non-specific attractive force
most important when numerous
atoms in one molecule come close
to atoms in another molecule

• The distribution of electric

charge around an atom changes
with time

• Thus, at any instant, charge

distribution is asymmetric. This
asymmetry around one atom
encourages similar asymmetry
around neighbouring atoms
leading to attraction
 Van der Waals Bonds (cont.)

• Attraction is distance dependent

• Strongly repulsive at short
internuclear distances and very weak
at long internuclear distances
• Attraction is maximal when two atoms
are separated by their Van der Waals
radii
• Van der Waals contact radius:
1.2-2.0 angstroms
• Van der Waals contact distance:
2.4-4.0 angstroms

• Weaker than electrostatic and H-

bonds with a bond energy of only 0.4
to 4 kJ/mol
 Hydrophobic Interactions

• Hydrophobic interactions are extremely important for the

folding of proteins into three-dimensional structures

• Hydrophobic amino acids are in the interior of the protein while

hydrophilic ones are solvent exposed

• Hydrophobic interactions
provide a “driving force” for the
proper folding of proteins in a
hierarchical manner
 Molecules having Both Hydrophilic and
Hydrophobic Properties
• Membrane phospholipids have both hydrophobic and hydrophilic
groups
• Important for the overall architecture of the lipid membrane
bilayer

• Sodium dodecyl
sulfate
• Synthetic detergent
• 12-carbon tail
• Polar sulfate group
 Biomolecules – Structure
Anabolic

• Building block • Macromolecule

• Simple sugar • Polysaccharide
• Amino acid • Protein (peptide)
• Nucleotide • RNA or DNA
• Fatty acid • Lipid

Catabolic

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 Nucleic Acids

•Store hereditary information

Contain information for making all the

body’s proteins

Two types exist --- DNA & RNA

 Nucleic Acids
-DNA & RNA are polymers

monomer nucleotide

polymer DNA

supramolecular
chromatin
structure
 Bases
• Four types of bases found in DNA

• Adenine and Guanine are classified as purines

• Cytosine and Thymine are pyrimidines
 Covalent Structure of DNA

• Each base is connected to a deoxyribose sugar which is

further connected to a phosphate backbone
• DNA has a polarity with one end called the 5’ end and the
other the 3’ end
 Numbering Convention of Sugar

• This figure shows the ribose sugar of RNA

• DNA lacks the hydroxyl group at the 2’ position
• The sugar is used as a reference point for the 5’ to 3’
directional polarity
 DNA Structure – 1953
-1953 - Crick and Watson publish double helix model
for DNA
-Nobel Prize - 1962
 “Photo 51”
-fiber diffraction pattern from Rosalind Franklin was crucial for Crick
and Watson to come up with the B-form double helix model
 Double Helix

• Double helical structure proposed by Watson and Crick

• Sugar-phosphate backbones shown in red and blue
• Two strands are antiparallel
 Erwin Chargaff (1905-2002)

• Looked at the percent composition of bases of

DNA in many different organisms

• In human DNA: A=30.9%, T=29.4%, G=19.9, and

C=19.8%

• Found that A=T and G=C across all domains of life

 Chargaff’s Rule

• This was crucial for the development of the DNA

double helix model
 Watson-Crick Base Pairs

• Adenine pairs with Thymine

• Guanine pairs with Cytosine
• Dashed green lines represent hydrogen bonds
• A-T has two hydrogen bonds
• G-C has three hydrogen bonds
 A and B form DNA

A-DNA B-DNA Z-DNA

-B-form is the predominant in vivo state of DNA

Major and Minor Grooves

Protein-DNA interactions
 DNA Structure and Replication
-Watson and Crick: the structure of DNA suggested a possible
copying mechanism

-if DNA is separated into two strands, each strand can act as the
template for the generation of its partner strand
The Human Genome Project

3 billion bases 30,000 genes

http://www.genome.gov/
 Genomics
• Study of sequences, gene organization &
mutations at the DNA level

• The study of information flow within a cell

• The Central Dogma

Central Dogma Genotype

RNA function &

structure
DNA
Protein sequence

RNA Protein structure

Protein Protein Function

Phenotype
 DNA Sequence Encodes Protein
Function
-the DNA sequence ultimately determines the structure and
function of proteins

-proteins are polymers of amino acids

-enzymes are proteins

 Impact of Genomics on Medicine

• How to characterize new diseases?

•
• What new treatments can be discovered?

• How do we treat individual patients? Tailoring

treatments?
 Implications for Biomedicine
• Physicians will use genetic information to
diagnose and treat disease.
• Virtually all medical conditions have
a genetic component
• Faster drug development research:
(pharmacogenomics)
• Individualized drugs
• All Biologists/Doctors will use gene
sequence information in their daily work
 RNA
-the addition of a hydroxyl group at the
2’ position of the ribose sugar adds
much greater functional and structural
versatility compared to DNA

-RNA can form a multitude of unique

folds and tertiary interactions

-many base pairing possibilities

-RNA can form base triples and base

quartets

-exists in predominately the A-form

 tRNA – from Cloverleaf to L-shape
-tRNA secondary structure - 1968
-two competing groups for tRNA crystal
structure in early 1970s:

-Aaron Klug - MRC Cambridge

-Alexander Rich - MIT
 Discovery of Catalytic RNAs
-Nobel Prize – 1989 – discovery that RNA can catalyze reactions
-Tom Cech – group I intron
-Sid Altman – Rnase P

Sid Altman Tom Cech