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Introduction to Biochemistry
Andy Howard
Biochemistry, Fall 2007
IIT
What is biochemistry?
By the end of biology 402 you should
be able to construct your own
definition; but for now:
 Biochemistry is the study of
chemical reactions in living tissue.

Plans

What is biochemistry?
 Organic and biochemistry
 Concepts from organic
chemistry to remember
 Small molecules and
macromolecules
 Classes of small molecules
 Classes of macromolecules
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Water
Catalysis
Energetics
Regulation
Molecular biology
Evolution
What will we study?

Biochemistry is the study of chemical
reactions in living tissue, both within cells and
in intercellular media.
 As such, it concerns itself with a variety of
specific topics:
Topics in biochemistry

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What reactions occur;
The equilibrium energetics and kinetics of those
reactions;
How the reactions are controlled, at the chemical and
cellular or organellar levels;
How the reactions are organized to enable biological
function.
Organic and biological chemistry

Most molecules in living things (other than
H2O and O2) contain C-C or C-H bonds, so
biochemistry depends heavily on organic
chemistry
 But the range of organic reactions that
occur in biological systems is fairly
limited compared to the full range of
organic reactions:
Why we use only a subset of
organic chemistry in biochem

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Biochemical reactions are almost always aqueous.
They occur within a narrow temperature and pressure
range.
They occur within narrowly buffered pH ranges.
Many of the complex reaction mechanisms
discovered and exploited by organic chemists since
the 1860's have no counterparts in the biochemical
universe.
Concepts from organic chemistry

There are some elements of organic
chemistry that you should have clear in your
minds.
 All of these are concepts with significance
outside of biochemistry, but they do play
important roles in biochemistry.
 If any of these concepts is less than
thoroughly familiar, please review it:
Organic concepts I

Covalent bond: A strong attractive interaction
between neighboring atoms in which a pair of
electrons is roughly equally shared between
the two atoms.
– Covalent bonds may be single bonds, in which
one pair of electrons is shared; double bonds,
which involve two pairs of electrons; or triple
bonds, which involve three pairs.
– Single bonds do not restrict the rotation of other
substituents around the bond; double and triple
bonds do.
Organic concepts II

Ionic bond: a strong
attractive interaction between
atoms in which one atom or
group is positively charged,
and another is negatively
charged.
Organic concepts III

Hydrogen bond: A weak attractive interaction
between neighboring atoms in which a hydrogen
atom carrying a slight, partial positive charge shares
that positive charge with a neighboring
electronegative atom.
– The non-hydrogen atom to which the hydrogen is covalently
bonded is called the hydrogen-bond donor;
– the neighboring atom that takes on a bit of the charge is
called the hydrogen-bond acceptor.

Van der Waals interaction: A weak attractive
interaction between nonpolar atoms, arising from
transient induced dipoles in the two atoms.
Organic Concepts IV


Chirality: The property of a molecule under which it
cannot be superimposed upon its mirror image.
Tautomerization: The interconversion of two
covalently different forms of a molecule via a
unimolecular reaction that proceeds with a low
activation energy. The two forms of the molecule are
known as tautomers: because of the low activation
barrier between the two forms, we will typically find
both species present.
Organic Concepts V

Nucleophilic substitution: a
reaction in which an electron-rich
(nucleophilic) molecule attacks an
electron-poor (electrophilic)
molecule and replaces group or
atom within the attacked species.
– The displaced group is known as a
leaving group.
– This is one of several types of
substitution reactions, and it occurs
constantly in biological systems.
Organic Concepts VI

Polymerization: creation of large
molecules by sequential addition of simple
building blocks
– often by dehydration, i.e., the elimination of
water from two species to form a larger one:
R1-O-H + HO-R2-X-H  R1-X-R2-OH + H2O
– The product here can then react with
HO-R3-X-H to form
R1-X-R2-X-R3-OH, and so on.
Organic Concepts VII


Equilibrium: in the context of a
chemical reaction, the state in which
the concentrations of reactants and
products are no longer changing with
time because the rate of reaction in
one direction is equal to the rate in the
opposite direction.
Kinetics: the study of the rates at
which reactions proceed.
Organic Concepts VIII

Catalysis: the lowering of the energetic barrier
between substrates and products in a reaction by the
participation of a substance that ultimately is
unchanged by the reaction
– It is crucial to recognize that catalysts (chemical agents that
perform catalysis) do not change the equilibrium position of
the reactions in which they participate:
– they only change the rates (the kinetics) of the reactions they
catalyze.

Zwitterion: a compound containing both a positive
and a negative charge
Classes of small molecules

Small molecules other than
water make up a small
percentage of a cell's mass, but
small molecules have significant
roles in the cell, both on their
own and as building blocks of
macromolecules. The classes of
small molecules that play
significant roles in biology are
listed below. In this list, "soluble"
means "water-soluble".
Biological small molecules I

Water: Hydrogen hydroxide. In liquid form in
biological systems. See below.
 Lipids: Hydrophobic molecules, containing
either alkyl chains or fused-ring structures. A
biological lipid usually contains at least one
highly hydrophobic moeity.
Biological small molecules II

Carbohydrates: Polyhydroxylated compounds
for which the building blocks are highly
soluble.
– The typical molecular formula for the monomeric
forms of these compounds is (CH2O)n, where 3 <
n < 9,
– but usually n = 5 or 6.
Biological small molecules III
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Amino acids: Compounds containing an
amine (NH3+) group and a carboxyl (COO-)
group.
The most important biological amino acids
are a-amino acids, in which the amine
group and the carboxyl group are separated
by one carbon, and that intervening carbon
has a hydrogen attached to it. Thus the
general formula for an a-amino acid is
H3N+ - CHR - COO-
Biological small molecules IV

Nucleic acids: Soluble compounds that
include a nitrogen-containing ring system.
– The ring systems are derived either from purine or
pyrimidine.
– The most important biological nucleic acids are
those in which the ring system is covalently
attached to a five-carbon sugar, ribose, usually
with a phosphate group attached to the same
ribose ring.
Small molecules V

Inorganic ions: Ionic species containing no
carbon but containing one or more atoms and
at least one net charge.
– Ions of biological significance include
Cl-, Na+, K+, Mg+2, Mn+2, I-, Ca+2, PO4-3, SO4-2,
NO3-, NO2-, and NH4+.
– Phosphate (PO4-3) is often found in partially
protonated forms HPO4-2 and H2PO4
– Ammonium ions occasionally appear as neutral
ammonia (NH3)
Biological Small Molecules VI

Cofactors: This is a catchall category for organic
small molecules that serve in some functional role in
biological organisms. Many are vitamins or are
derived from vitamins; a vitamin is defined as an
organic molecule that is necessary for metabolism
but cannot be synthesized by the organism. Thus the
same compound may be a vitamin for one organism
and not for another. Ascorbate (vitamin C) is a
vitamin for humans and guinea pigs but not for most
other mammals. Cofactors often end up as prosthetic
groups, covalently or noncovalently attached to
proteins and involved in those proteins' functions.
Biological macromolecules
Most big biological molecules are
polymers, i.e. molecules made up of
large numbers of relatively simple
building blocks.
 Cobalamin is the biggest
nonpolymeric biomolecule I can
think of (MW 1356 Da)

Categories of biological polymers
Proteins
 Nucleic acids
 Polysaccharides
 Lipids (sort of):

– 2-3 chains of aliphatics attached to a
polar head group, often built on glycerol
– Aliphatic chains are usually 11-23 C’s
Polymers and oligomers
These are distinguished only by the
number of building-blocks contained
within the multimer
 Oligomers: typically < 50 building
blocks
 Polymers  50 building blocks.
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Categories of biopolymers
Category
Protein
# monomers
20
<mol wt/
# mono- Branchmonomer> mers
ing?
110
65-5000 no
RNA
4-10
220-400
50-15K
no
DNA
4
200-400
50-106
no
Polysaccharide
~10
180
2-105
Sometimes
Water: a complex substance

Oxygen atom is covalently bonded to two
hydrogens
 Single bond character of these bonds
means the H-O-H bond angle is close to
109.5º = acos(-1/3)
 This contrasts with O=C=O (angle=180º) or
urea ((NH2)2-C=O)
(angles=120º)
 Two lone pairs available per oxygen:
these are available as H-bond acceptors
Water is polar

Charge is somewhat unequally shared
 Small positive charge on H’s (d+); small
negative charge on O (2d-)
 A water molecule will orient itself to align
partial negative charge on one molecule
close to partial positive charges on
another.
 Hydrogen bonds are involved in this.
Liquid water is mobile
The hydrogen-bond networks
created among water molecules
change constantly on a subpicosecond time scale
 At any moment the H-bonds look like
those in crystalline ice
 Solutes disrupt the H-bond networks

Water in reactions

Water is a medium within which reactions
occur;
 But it also participates in reactions
 Enzymes often function by making water
oxygen atoms better nucleophiles or water
H’s better electrophiles
 Therefore water is a direct participant in
reactions that wouldn’t work in a
nonenzymatic lab setting!
Water’s physical properties
High heat capacity:
stabilizes temperature in living
things
 High surface tension
 Nearly incompressible (density
almost independent of pressure)
 Density max at 3.98ºC

Catalysis
Catalysis is the lowering of the
activation energy barrier between
reactants and products
 How?

– Physical surface on which reactants
can be exposed to one another
– Providing moieties that can temporarily
participate in the reaction and be
restored to their original state at the end
Biological catalysts
1890’s: Fischer realized that there had to
be catalysts in biological systems
 1920’s: Sumner said they were proteins
 It took another 10 years for the whole
community to accept that
 It’s now known that RNA can be catalytic
too:

– Can catalyze modifications in itself
– Catalyzes the key step in protein synthesis in
the ribosome
Energy in biological systems
We distinguish between
thermodynamics and kinetics:
 Thermodynamics characterizes the
energy associated with equilibrium
conditions in reactions
 Kinetics describes the rate at which a
reaction moves toward equilibrium

Thermodynamics
Equilibrium constant is a measure of
the ratio of product concentrations to
reactant concentrations at
equilibrium
 Free energy is a measure of the
available energy in the products and
reactants
 They’re related by DGo = -RT ln Keq

Kinetics
Rate of reaction is dependent on
Kelvin temperature T and on
activation barrier DG‡ preventing
conversion from one site to the other
 Rate = Qexp(-DG‡/RT)
 Job of an enzyme is to reduce DG‡

Regulation

Biological reactions are regulated in the
sense that they’re catalyzed by enzymes,
so the presence or absence of the enzyme
determines whether the reaction will
proceed
 The enzymes themselves are subject to
extensive regulation so that the right
reactions occur in the right places and
times
Typical enzymatic regulation
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Suppose enzymes are involved in converting A to
B, B to C, C to D, and D to F. E is the enzyme that
converts A to B:
(E)
ABCDF
In many instance F will inhibit (interfere) with the
reaction that converts A to B by binding to a site
on enzyme E so that it can’t bind A.
This feedback inhibition helps to prevent
overproduction of F—homeostasis.
Molecular biology
This phrase means something much
more specific than biochemistry:
 It’s the chemistry of replication,
transcription, and translation, i.e., the
ways that genes are reproduced and
expressed.
 Most of you have taken biology 214 or
its equivalent; we’ll review some of
the contents of that course here.

The molecules of molecular bio

Deoxyribonucleic acid: polymer;
backbone is deoxyribose-phosphate; side
chains are nitrogenous ring compounds
 RNA: polymer; backbone is ribosephosphate; side chains as above
 Protein: polymer: backbone is
NH-(CHR)-CO; side chains are 20
ribosomally encoded styles
Steps in molecular biology

DNA replication (makes accurate copy of
existing double-stranded DNA prior to
mitosis)
 Transcription (RNA version of DNA
message is created)
 Translation (mRNA copy of gene serves as
template for making protein: 3 bases of
RNA per amino acid of synthesized rotein)
Evolution and Taxonomy

Traditional studies of interrelatedness of
organisms focused on functional
similarities
 This enables production of phylogenetic
trees
 Molecular biology provides an alternative,
possibly more quantitative, approach to
phylogenetic tree-building
 More rigorous hypothesis-testing possible