Goals of the Course
• Introduce the
of biochemistry:
– vocabulary (terms and structures)
– grammar (reactions)
– sentence structure (pathways)
– meaning (metabolic interrelationships)
• Emphasize underlying unity and concepts
• Convey an appreciation for how much you will have learned, and how much more there is to know
Chapter 1 1
Encouraged Study Habits
• Read chapters in advance
• Study at least 3 hours per lecture
• Work lots of problems (use the study guide!)
• Memorize terms, structures, and pathways
•
Chapter 1 2
1

The Question of Structure
• You will have to reproduce
of the complex biochemical structures we come into contact with in this course, you should
think about things like:
– How a compound’s concentration might change in response to certain metabolic conditions
– How aspects of a compound’s structure contribute to its biological function
– In what pathway(s) a compound occurs (where did it come from; where can it go?)
Chapter 1 3
2

What are we studying?
• What are the similarities between a frog and a car?
• How are they the different?
• Biochemistry is the study of how a collection of inanimate molecules interact to form, maintain and perpetuate animated life solely by obeying the physical and chemical laws that govern the universe
Chapter 1 5
So, what is Life ?
• Biological organisms possess amazing characteristics that distinguish them from other collections of matter.
• Any ideas?
Chapter 1 6
3

Features of Life
Life requires a high degree of chemical complexity and microscopic organization
Life requires systems for extracting, transforming and using energy from the environment
Life requires a capacity for precise self-replication and selfassembly
Chapter 1 7
Features of Life
Life requires mechanisms for sensing and responding to alterations in their environment
Life requires defined functions for each of their components and regulated interactions among them
Life requires a history of evolutionary change
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4

Cellular Foundations of Life
Cells are the structural and functional units of all living organisms
Chapter 1
Cellular Foundations of Life
• There are three distinct domains of life:
– Archbacteria
Prokaryotes
– Eubacteria
– Eukaryotes
9
Chapter 1 10
5

Cellular Foundations of Life
Chapter 1
Cellular Foundations of Life
• We can further classify organisms according to how they obtain the energy and carbon they need for synthesizing cellular material
Chapter 1 12
11
6

Cellular Foundations of Life
Chapter 1
Cellular Foundations of Life
13
Chapter 1 14
7

Cellular Foundations of Life
Chapter 1
Cellular Foundations of Life
15
Chapter 1 16
8

Cellular Foundations of Life
Chapter 1 17
Chemical Foundations of Life
“What is true of E. coli is true of the elephant” - Jacques Monod
Biochemistry aims to explain biological function and form in chemical terms
99% of a biological cell is composed of
H, O, N and C
Chapter 1
Element
H
O
N
C
# unpaired e’s
1
2
3
4
Fractional amount
2/3
1/4
1/70
1/10 18
9

Chemical Foundations of Life
The Versatile Carbon Atom is the Backbone of Life
• Carbon has four valence electrons capable of forming covalent bonds.
• If the four bonds are arranged tetrahedrally, there is a bond angle of ~109.5° and a bond length of ~0.154 nm.
• This arrangement also allows for free rotation around each single bond unless there are highly charged or bulky groups attached.
• A double bond is shorter (~0.134 nm) and more rigid, allowing little rotation about its axis
Chapter 1 19
Chemical Foundations of Life
Common Functional Groups
Chapter 1 20
10

Chemical Foundations of Life
Biomolecules are not limited to a single functional group
• Most Biomolecules are merely derivatives of hydrocarbons where hydrogen atoms have been replaced by one or more functional groups.
• The variety of functional groups and the ability of hydrocarbons to form chains (branched or unbranched) or cyclic compounds allows for amazing molecular diversity
Chapter 1 21
Chemical Foundations of Life
• The covalent linkage and functional groups of biochemicals are important, but so is the 3-D structure or configuration of the molecule.
• Configuration of a biomolecule (as with all molecules!) is determined by the presence of either:
– Double Bonds (no freedom of rotation)
• Geometric Isomers
– Chiral Centers
• Stereoisomers
Chapter 1 22
11

Chemical Foundations of Life
• Interconversion between species requires breaking covalent bonds
• In general, these isomers can be separated from one another, and have unique chemical properties.
• A binding site that is complimentary to one isomer would not be suitable for the other.
• Therefore, these isomers have distinct biological activities
Chapter 1 23
Chemical Foundations of Life
• A carbon atoms with four different substituents represents a chiral center
• A molecule with one chiral center can have two stereoisomers.
• When two or more centers (n) are present, there can be 2 n stereoisomers.
Chapter 1 24
12

Chemical Foundations of Life
• The stereoisomers can be either:
– Enatiomers: mirror images of each other
– Diastereomers: non-mirror images
Chapter 1 25
Chemical Foundations of Life
• Assign a priority to each group attached to a chiral carbon based upon atomic mass priority (1 highest, 4 lowest)
• If two atoms are identical, move to the next atom(s)
• For double or triple bonds, count atom once for each bond (-CHO higher priority than -CH
2
OH)
• Priorities (low to high):
-H < -CH
3
< -CH
2
OH < -CHO < -COOH < -NH
2
< -OH < -OCH
2
• Orient the molecule with priority 4 pointing away (behind the chiral carbon).
• Trace path from highest priority to lowest priority (1, 2, 3, 4)
• Clockwise path: absolute configuration R
• Counterclockwise path: absolute configuration S
Chapter 1 26
13

Chemical Foundations of Life
What would the structure of (R) – Glyceraldehyde look like?
27 Chapter 1
Chemical Foundations of Life
• Distinct from the configuration of a biomolecule is its conformation .
• The conformation of a molecule is the spatial arrangement of substitutent groups that, without breaking any bonds, are free to assume in space due to the freedom of rotation about single bonds.
Chapter 1 28
14

Chemical Foundations of Life
Interactions between Biomolecules are Stereospecific
• The 3-D structure of a biomoleucle is very important in defining its biological interactions:
– Reactant with an enzyme
– Hormone with its receptor
– Antigen with its antibody
• Stereospecificity is a property of enzymes and other proteins and a characteristic feature of the molecular logic of living cells.
• In living organisms, chiral molecules are usually present in only one of its chiral forms (waste not, want not!)
• Very different from what we produce in a lab when synthetically producing analogs of biological chemicals.
Chapter 1 29
Physical Foundations of Life
• All living organisms must perform work to stay alive and reproduce.
• All of the biological processes, including movement, storage / expression of information and synthetic reactions, that occur within a cell require energy just like your work at the bench.
• Through the course of evolution, cells have developed highly efficient mechanisms for the coupling of the energy obtained from sunlight or fuels to the many energy consuming processes they must carry out.
• Like any other chemical process, we can consider cellular energy conversion of biological systems in the context of the laws of thermodynamics
Chapter 1 30
15

Physical Foundations of Life
Living organisms are never at equilibrium with their surroundings – until they are dead
• The characteristic composition of an organism changes little through time, the population of molecules within the system is in a constant state of flux.
• Molecules are constantly being synthesized, transported, utilized and degraded.
• The concentration of these compounds does remain more or less constant (or you are in big trouble!) indicating the maintenance of these levels is highly controlled by the system.
• This dynamic steady state requires constant input of energy
• Once the energy runs out ( i.e.
the cell begins to die), the organism begins to decay towards equilibrium with its surroundings
Chapter 1 31
Physical Foundations of Life
1 st Law of Thermodynamics
In any physical or chemical change, the total amount of energy in the universe remains constant, although the form of that energy may change
• The system is the specific part of the universe that is of interest to us ( i.e.
the reaction with reactants & products) and the surroundings is the rest of the universe
• If the system exchanges neither matter nor energy with its surroundings, it is an isolated system
• If the system exchanges only energy with its surroundings, it is a closed system
• If the system exchanges both matter and energy with its surroundings, it is an open system
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16

Physical Foundations of Life
2 nd Law of Thermodynamics
The total entropy increases in a spontaneous process and remains unchanged in an equilibrium process.
• Gibbs Free Energy Change ( ∆ G) weighs the relative contributions of enthalpy and entropy of the systems to the overall spontaneity of a process.
∆ G = ∆ H – T ∆ S
∆ G < 0
∆ G = 0
∆ G > 0
Spontaneous
Equilibrium
Non-spontaneous
Chapter 1 33
Physical Foundations of Life
2 nd Law of Thermodynamics
• DNA, RNA and proteins are informational polymeric macromolecules. For these molecules, the order of the monomeric units composing the macromolecule is important.
• Therefore, the system must use chemical energy not only to form covalent bonds between the monomers, but to order these units in the correct sequence.
• This type of synthesis leads to a decrease in the disorder of the system meaning that free energy must be provided to the system
• For the spontaneous formation of more ordered macromolecules (like DNA), cells must couple the energy requiring reaction ( endergonic ) to another reaction that liberates free energy ( exergonic )
• This coupling results in an overall negative free energy change!
Breakage of the phosphoanhydride bond in Adenosine triphosphate (ATP) is the cell’s go-to exergonic reaction
∆
G = -30.5 kJ/mol
34 Chapter 1
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Physical Foundations of Life
Life uses chemical coupling to drive otherwise unfavorable reactions
Exergonic (Catabolism) – Energy PRODUCING
Entergonic (Anaboism) – Energy REQUIRING
Chapter 1 35
Physical Foundations of Life
Life uses enzymes to speed up otherwise slow reactions
• Enzymes are proteins that catalyze a specific chemical reaction.
• These proteins are built to interact with a specific substrate.
• Most pharmaceutical compounds are synthesized to mimic an enzyme target
36 Chapter 1
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Genetic Foundations of Life
Genetic Memory – Deoxyribonucleic Acid (DNA)
• DNA is a polymeric molecule composed of a sequence of monomeric deoxyribonucleotide units attached through a phosphodiester bond.
• The sequence of these units encodes the instructions for forming all other cellular components and provides a template for the production of identical DNA strands for distribution during cell division.
• Your DNA is a single, very large molecule
(can be many centimeters long).
• A human sperm cell contains a single molecule of DNA in each of the 23 chromosomes which match up with the corresponding DNA molecules of the egg.
• Viola! You are produced!
Chapter 1 37
Genetic Foundations of Life
Deoxyribonucleic Acid (DNA)
Chapter 1
• The bases of DNA utilize hydrogen bonding interactions to form complimentary strands across the double helix
A – T This pair has two hydrogen bonds
G – C This pair has three hydrogen bonds
38
19

Genetic Foundations of Life
• The linear DNA molecule is arranged into discrete units known as genes
• Each gene is transcribed into a molecule of ribonucleic acid (RNA) that is complimentary to the DNA strand.
• This messenger RNA molecule (mRNA) is translated into a linear protein strand.
• The linear protein then folds (based on the sequence of the protein and other environmental factors) into its native 3-D structure
• This mature protein can then interact with other proteins to form macromolecular structures
Chapter 1 39
Evolutionary Foundations of Life
DNA Infidelity - Mutations
• Despite near-perfect reproduction of your DNA molecules, unrepaired mistakes can lead to alterations in the
DNA sequence, producing a genetic mutation
• These mutations (if uncorrected) will be passed down to cellular offspring and can be harmful to the organism as a whole.
• The unmutated version of the DNA is often termed wild type with the mutated versions called the mutants
Why do you think mutations could be bad?
Can mutations ever be good?
Chapter 1 40
20

Evolutionary Foundations of Life
The Beginning of Life – Abiotic Origins
• In the 1920s, Aleksandr Oparin proposed the Abiotic Hypothesis for the beginnings of life on earth.
• Basically, electrical and/or heat energy in conjunction with a reducing atmosphere (lots of CH
4
, NH
3 and H resulting in the production of simple
2
O) organic compounds.
• These compounds were dissolved into the warm ancients seas where some associated into larger complexes (think
DNAs, proteins, etc.)
• Over millions of years, these in turn assembled to form membranes and catalysts (enzymes), which formed the earliest cells.
Chapter 1 41
Evolutionary Foundations of Life
The Beginning of Life – The RNA World Scenario
Chapter 1 42
21

Evolutionary Foundations of Life
The Genome
• Carolus Linnaeus and Charles Darwin both recognized the anatomic similarities and differences among organisms which led to the idea of a common ancestor
• Modern science determined that the complete genetic information for an organism can be found in its genome
• The sequence of the genome of numerous organisms in now known and comparison of these sequences is leading to information on the evolutionary process.
• Molecular phylogeny (the classification of an organsim based on genetic info) is proving to be consistent with classical phyolgeny (based on visible traits) but appears to be more precise.
Chapter 1 43
Evolutionary Foundations of Life
The Genome
• When two genes share detectable sequence similarities, the are homologous and the proteins they encodes are called homologs
• If two homologous genes reside within the same species, they are termed paralogous and they encode protein paralogs
• If two homologous genes reside within the different species, they are termed orthologous and they encode protein orthologs 44 Chapter 1
22

Evolutionary Foundations of Life
Genomics
• Once the genomic sequence of an organism if fully determined AND annotated (each gene is assigned a function), we can group genes according to function
• The largest functional category for the genes in the human genome is “unknown function” making up about 40% of the genes (See, lots of work to do for the Biochemists!)
• Other gene categories include:
– Ion transporters: ~ 4%
– Proteins and RNA required for protein synthesis: ~ 5%
• In general, the more complex the organism, the higher the proportion of its genome that encodes genes involved in the regulation of cellular processes and the lower the proportion dedicated to the basic processes themselves
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