Table of Contents
Fundamentals of Biochemistry
Biochem 380 - Fall 2006
Lecture 002
Outline
- Announcements
- Section 1: History of Biochemistry
- Section 2: The Chemical Elements of Life
- Section 3: Biopolymers
- Section 4: Energy and Thermodynamics
Announcements
- Office hours this week by appt. only
- The course web pages are online
- Exams are in the evenings on Thursdays
Section 1: History of Biochemistry
- Biochemistry is a fairly new field of science, developed largely in the 20th century
- However, the first landmark of biochemistry was Wohler's synthesis of the organic compound urea
from the inorganic precursor ammonium cyanate
- This demonstrated that the building blocks of life were the same as those of non-living things (no vitalism needed)
- Similarly, Buchner showed that a process of biochemistry, catalysis, could also occur independently
from living cells (enzymes in yeast extracts and fermentation)
- Fischer did further analysis of enzymes (hydrolysis of sucrose) and developed the lock and key model
(enzyme as rigid lock, substrate as key)
- A modified version of this model (induced fit) is still used today
The DNA Breakthrough
- Another huge landmark in biochemistry took place in the 1940's and 1950's, involving DNA
- Avery et al. showed that DNA is the genetic material that determines the traits (phenotype) of organisms
- Their experiments demonstrated the transformation of a non-toxic strain of Streptococcus pneumoniae
by adding DNA from a toxic strain
- Then, in 1953, Watson and Crick made their famous discovery of the structure of DNA
- The sequence of base pairs in a double helical structure provided an explanation for how
information could be stored and reproduced
- Crick's Central Dogma: DNA -> RNA -> Protein
Section 2: The Chemical Elements of Life
- There are 6 primary elements found in living organisms:
- Oxygen
- Carbon
- Hydrogen
- Nitrogen
- Phosphorus
- Sulfur
- These account for about 97% (by weight) of the material in most organisms
5 Essential Ions of Life
- There are also 5 common ions found in all organisms:
- Calcium (Ca2+)
- Potassium (K+)
- Sodium (Na+)
- Magnesium (Mg2+)
- Chloride (Cl-)
The 29 Common and Trace Elements
- In total, there are 29 elements found:
Types of Organic Compounds
- The elements of life are assembled into molecules with common structures and patterns
- These include the familiar types that we have seen in Organic Chemistry:
- Organic Compounds
- Functional Groups
- Linkages
Organic Compounds
- In vivo, carboxylic acids typically are found in the ionized state as carboxylate ions (COO-)
- Similarly, amines exist as ammonium ions (NH4+)
Functional Groups
- When these organic compounds are bonded to other atoms, they can be identified as
characterisitc functional groups:
- We will encounter each of these functional many times in various kinds of biomolecules
Linkages
- In biomolecules, there are also bonds involving particular groups of atoms that are seen over and over again.
They include the following kinds of linkages:
- Esters and ethers are seen in fatty acids and lipids. Amides are found in proteins, and the phosphate and
phosphoanhydride linkages are seen in nucleic acids
Section 3: Biopolymers
- All four main categories of biomolecules include instances of very large molecules (macromolecules)
- Such macromolecules are commonly constructed as polymers
- This demonstrates a common theme in biochemistry, modular construction, where smaller molecules
are joined together to form larger structures
- In the case of polymers, they are formed from smaller molecules called monomers that are linked together in a
sequential way to form long chains
- After being joined together, the individual monomers in a chain are referred to as residues
- Because each end of a monomer is typically distinct from the other end, the ends of the resulting
polymer chain are also different, giving it a characteristic direction
Molecular Weights of Biopolymers
- Because a single biomolecule such as a polymer can consist of many hundreds or thousands of atoms bonded
together, it will consequently have a very large molecular weight
- The molecular weight (or more precisely, the relative molecular mass, Mr) is the ratio
of the mass of a molecule to 1/12 the mass of a 12C carbon atom
- The text makes the clear distinction between this unitless ratio and the absolute molecular mass
- The mass of a chemical compound can refer to the mass of a single molecule. Then, we
refer to the mass in daltons, where a dalton is 1 atomic mass unit (approximately the mass of a hydrogen atom)
- At the macroscopic level, we refer to the mass of a mole (6.023 x 1023) of molecules
(the molar mass), with units of g/mol (grams per mole).
- For large molecular weights of biomolecules such as proteins, the molar mass is
expressed in kg/mol. For example, a typical protein with a mass of 38,000 daltons would have a molar mass of 38 kg/mol
Some Examples of Macromolecules
- We will take a brief look at some macromolecules from each of the four classes of biomolecules
- Later, we'll study them in much more detail
- Proteins, polysaccharides and nucleic acids are all examples of macromolecules that are polymers
- Lipids are a little different, as they form large structures called membranes
- These are not polymers, but instead are aggregates of closely associated lipid molecules
Proteins
- Proteins are polymers formed from the condensation of individual amino acids:
- The amino group from one amino acid reacts with the carboxylate group of the other to
form an amide linkage that is referred to as a peptide bond
- The amino acids are combined in a specific sequence to produce proteins consisting of hundreds
or thousands of amino acid residues
Polysaccharides
- Polysaccharides are carbohydrates formed from simple sugars (monosaccharides):
- Here, two glucose molecules are combined by a reaction between the C-1 carbon of one glucose with
a hydroxyl group of the other to form a glycosidic bond
Nucleic Acids
- Nucleic acids are polymers formed from monomers called nucleotides that are joined in a
phosphodiester linkage:
Lipids and Membranes
- Lipids are molecules used to form aggregate structures such as cell membranes. A common type of lipid are
the glycerophospholipids, which are composed of long fatty acyl tails attached to a glycerol platform, in
turn connected via a phosphate ester linkage to a polar head group
Section 4: Energy and Thermodynamics
- We won't be going into thermodynamics too heavily in this course, but there are some basic concepts
that are important to understand
- These include:
- Reactions and reaction rates
- Equilibrium and the equilibrium constant (Keq)
- Gibbs Free Energy (G)
- The Standard Gibbs Free Energy (G') and the effect of changes of concentration
Reactions and Rate Constants
- A reaction of two reactants A and B that form two different products C and D can be shown as
- A + B → C + D
- The rate of the reaction is determined by the concentrations of the reactants, [A] and [B],
and also by the intrinsic reactivity, expressed as a rate constant, k
- Higher concentrations of the reactants will result in higher rates in which the products are produced
- As products are created however, the reverse reaction will also occur, where A and B are produced from C and D
Equilibrium
- At some point, the concentrations of reactants and products will be such that the forward and reverse reactions
are balanced, so that the concentrations are no longer changing
- This is referred to as equilibrium
- The ratio of concentrations of products to that of reactants is defined as the equilibrium constant (Keq):
- Keq = [C][D] / [A][B]
Gibbs Free Energy
- The Gibbs free energy G is used to describe the change in energy between the reactants and products of a reaction
- The change in free energy, ΔG, has two components: the change in enthalpy (heat content) ΔH
and the change in entropy (information content) ΔS:
- ΔG = ΔH - TΔS
- If the ΔG of a reaction is negative, the reaction can occur spontaneously
- If ΔG is positive, the reaction will not occur
Standard Free Energy and Concentrations
- The change in free energy of a reaction can be measured under standard conditions to give a
quantitative value called the standard free energy, ΔG'
- Then, the actual free energy, ΔG can be expressed in terms of this standard free energy
and the actual concentrations of a reaction, as follows:
- ΔG = ΔG' + RT ln ([C] [D] / [A] [B])
- The important point to note is that the actual free energy can be made negative (favorable) if necessary,
by changing the relative concentrations of the reactants and products, even if the standard free energy is not negative
- In living organisms, many reactions that would normally be unfavorable can be made favorable in this way
Questions
Next Lecture: Sections 1.5 - 1.10
References
- Book: The 8th day of Creation, by Horace Judson
A very readable and interesting book that gives a history of biochemistry and molecular biology
in great detail
- Book: For the Love of Enzymes, by Arthur Kornberg
An autobiography of a great biochemist who discovered DNA Polymerase, it gives a nice history
of the 'Enzyme hunters' of biochemistry