Transcript Biochemical Thermodynamics - Illinois Institute of Technology

Introduction to Biochemistry
Andy Howard
Biochemistry, Fall 2010
IIT
7/21/2015
Biochemistry: Introduction
1
What is biochemistry?
By the end of this course you should
be able to construct your own
definition; but for now:
 Biochemistry is the study of
chemical reactions in living tissue.

7/21/2015
Biochemistry: Introduction
p. 2 of 51
Plans






What is biochemistry?
Cells
Cell components
Organic and
biochemistry
Concepts from organic
chemistry to remember
Small molecules and
macromolecules
7/21/2015

Classes of small
molecules
 Classes of
macromolecules
 Water
 Catalysis
 Energetics
 Regulation
 Molecular biology
 Evolution
Biochemistry: Introduction
p. 3 of 51
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:
7/21/2015
Biochemistry: Introduction
p. 4 of 51
Topics in biochemistry




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 within the cell and in
tissues and organisms.
7/21/2015
Biochemistry: Introduction
p. 5 of 51
Organic and biological chemistry

Most molecules in living things
(other than H2O, O2, and CO2)
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:
7/21/2015
Biochemistry: Introduction
p. 6 of 51
Why we use only a subset of
organic chemistry in biochemistry




Biochemical reactions are
almost always aqueous.
Frederich
They occur within a narrow temperature and
Wöhler
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.
7/21/2015
Biochemistry: Introduction
p. 7 of 51
Cells
Most biochemical reactions (but not all!)
take place within semi-independent
biological entities known as cells
 Cells in general contain replicative and
protein-synthetic machinery in order to
reproduce and survive
 They often exchange nutrients and
information with other cells

7/21/2015
Biochemistry: Introduction
p. 8 of 51
Cell components
Cells are separated from their
environments via a selectively porous
membrane
 Individual components (often called
organelles) within the cell may also
have membranes separating them from
the bulk cytosol and from one another

7/21/2015
Biochemistry: Introduction
p. 9 of 51
Eukaryotes and prokaryotes
The lowest-level distinction among
organisms is on the basis of whether
their cells have defined nuclei or not
 Cells with nuclei are eukaryotic
 Cells without nuclei are prokaryotic
 Eubacteria and archaea are prokaryotic
 Other organisms (including some
unicellular ones!) are eukaryotic

7/21/2015
Biochemistry: Introduction
p. 10 of 51
Eukaryotic organelles I
Nucleus: contains genetic information;
site for replication and transcription
 Endoplasmic reticulum: site for protein
synthesis and protein processing
 Ribosome: protein-synthetic machine
 Golgi apparatus: site for packaging
proteins for secretion and delivery

7/21/2015
Biochemistry: Introduction
p. 11 of 51
Eukaryotic organelles II

Mitochondrion: site for most energyproducing reactions
 Lysosome: digests materials during
endocytosis and cellular degradation
 Peroxisome: site for oxidation of some
nutrients and detoxification of the H2O2
created thereby
 Cytoskeleton: network of filaments that
define the shape and mobility of a cell
7/21/2015
Biochemistry: Introduction
p. 12 of 51
Eukaryotic organelles III
Chloroplast:
site for most photosynthetic reactions
 Vacuoles:
sacs for water or other nutrients
 Cell wall: bacterial or plant component
outside cell membrane that provides
rigidity and protection against osmotic
shock

7/21/2015
Biochemistry: Introduction
p. 13 of 51
Molecular machines




Cells contain components featuring enzymedriven molecular machines that accomplish
specific tasks
Usually too small and too internalized within
cells or organelles to be considered as
organelles themselves, but they’re still
important
Examples: proteasome, spliceosomes, fatty
acid synthases
Ribosomes are borderline between organelles
and molecular machines
7/21/2015
Biochemistry: Introduction
p. 14 of 51
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:
7/21/2015
Biochemistry: Introduction
p. 15 of 51
Organic
concepts I
Image courtesy Michigan State U.

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 (see above).
– Single bonds do not restrict the rotation of other
substituents around the bond; double and triple
bonds do.
7/21/2015
Biochemistry: Introduction
p. 16 of 51
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.
7/21/2015
Biochemistry: Introduction
p. 17 of 51
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.
Cartoon
courtesy
CUNY
Brooklyn
– The non-hydrogen atom to which the hydrogen
is covalently bonded is called the hydrogenbond donor;
– the neighboring atom that takes on a bit of the
charge is called the hydrogen-bond acceptor
7/21/2015
Biochemistry: Introduction
p. 18 of 51
Organic
concepts IV

Van der Waals
interaction:
A weak attractive
interaction between
nonpolar atoms,
arising from
transient induced
dipoles in the two
atoms.
7/21/2015
Image courtesy
Columbia U. Biology Dept.
Biochemistry: Introduction
p. 19 of 51
Organic
Concepts V

Chirality: The property of
a molecule under which it
cannot be superimposed
upon its mirror image.
Image courtesy DRECAM, France
7/21/2015
Biochemistry: Introduction
p. 20 of 51
Organic
Concepts VI

acetone
propen-2-ol
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.
7/21/2015
Biochemistry: Introduction
p. 21 of 51
Organic Concepts
VII

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.
7/21/2015
Biochemistry: Introduction
p. 22 of 51
Organic Concepts VIII

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 with elimination of another
water molecule, and so on.
7/21/2015
Biochemistry: Introduction
p. 23 of 51
Organic Concepts IX



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.
Conventionally, we use the term thermodynamics
to describe our understanding of the energetics of
equilibrium systems
7/21/2015
Biochemistry: Introduction
p. 24 of 51
Organic Concepts X

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
7/21/2015
Biochemistry: Introduction
p. 25 of 51
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".
7/21/2015
Biochemistry: Introduction
p. 26 of 51
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.
7/21/2015
Biochemistry: Introduction
p. 27 of 51
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 = 3, 5 or 6.
7/21/2015
Biochemistry: Introduction
p. 28 of 51
Biological small molecules III



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-
7/21/2015
Biochemistry: Introduction
p. 29 of 51
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.
7/21/2015
Biochemistry: Introduction
p. 30 of 51
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), particularly at higher pH values
7/21/2015
Biochemistry: Introduction
p. 31 of 51
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 in small quantities
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.
7/21/2015
Biochemistry: Introduction
p. 32 of 51
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)

7/21/2015
Biochemistry: Introduction
Structure
courtesy
Wikimedia
p. 33 of 51
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
7/21/2015
Biochemistry: Introduction
p. 34 of 51
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.

7/21/2015
Biochemistry: Introduction
p. 35 of 51
Categories of biopolymers
Category
Protein
# monomers
20
<mol wt/
monomer>
110
# monomers
65-5000
Branching?
no
RNA
4-10
220-400
50-15K
no
DNA
4
200-400
50-106
no
Polysaccharide
~10
180
2-105
Sometimes
7/21/2015
Biochemistry: Introduction
p. 36 of 51
Water: a complex substance




Oxygen atom is covalently bonded to 2
hydrogens
Single bond character of these bonds means the
H-O-H bond angle is close to 109.5º = acos(-1/3):
actually more like 104.5º
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
7/21/2015
Biochemistry: Introduction
p. 37 of 51
Water is polar
Charge is somewhat unequally shared
 Small positive charge on H’s (d+); small
negative charge on O (2d-) (Why?)
 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.

7/21/2015
Biochemistry: Introduction
p. 38 of 51
Liquid water is mobile
The hydrogen-bond networks created
among water molecules change
constantly on a sub-picosecond time
scale
 At any moment the H-bonds look like
those in crystalline ice
 Solutes disrupt the H-bond networks

7/21/2015
Biochemistry: Introduction
p. 39 of 51
Mathematics in biochemistry

Biochemistry is fundamentally an empirical
discipline and is highly dependent on
quantitative experiments
 Many branches of mathematics are relevant
to biochemical research
 In this class we will rarely go beyond high
school algebra (including logarithms and
exponentials), but you’d better be comfortable
with those
7/21/2015
Biochemistry: Introduction
p. 40 of 51
Course structure

I teach biology 401 all semester;
Prof. Nicholas Menhart teaches the followup
course, biology 402, which focuses on
specific metabolic systems
 We will introduce general concepts of
metabolism this semester without going into
specific systems
 We’ll spend a fair amount of time discussing
techniques and analytical approaches, which
will be instantiated in 402
7/21/2015
Biochemistry: Introduction
p. 41 of 51
Examination plans

Two midterms (9/24, 10/29) plus a final
– My exams will be closed-book, closed-notes
exams. Calculators are not allowed.
– You’ll have a help-sheet for each of my exams
– Gauge your memorization with the help-sheet
before you: what’s on the help sheet doesn’t need
to be memorized
– My exams tend to be long but easy:
budget your time carefully!
– Final exam date will be set by Registrar soon
7/21/2015
Biochemistry: Introduction
p. 42 of 51
Grading




I’m a moderately tough grader, but I do
curve this course
Curving is relative to students over several
years of performance, not just this year
The cutoff for an A is likely to be around an
82, but it’s uncertain
Homework, literature assignments, iClicker
quizzes, and discussion-board participation
count; see Blackboard site for details
7/21/2015
Biochemistry: Introduction
p. 43 of 51
Textbook and Lecture Notes




Required textbook: Garrett & Grisham,
Biochemistry, either expanded 3rd ed. or 4th ed.
It’s a detail-rich text and is clearly written.
You may wish to examine Horton, Principles of
Biochemistry, which is somewhat shorter
Most of my lectures are derived from G&G, but I’ll
often give cross references to Horton
Be prepared for the lecture notes themselves to
evolve during the course; they’re all posted, but I
will generally revise them the day that I deliver
the lecture.
7/21/2015
Biochemistry: Introduction
p. 44 of 51
Office Hours

Life Sciences Room 174
 I should be available 3:30pm-6pm Tuesdays
and Thursdays and often from 11am to 1pm
as well
 If that doesn’t work, make an appointment:
[email protected]
office 312-567-5881, cell 773-368-5067
 The discussion board is another good way to
reach me and the rest of the class as well!
7/21/2015
Biochemistry: Introduction
p. 45 of 51
Assignments
Regular homeworks will be due weekly,
generally on Fridays
 But no assignment due this week
 Literature assignments are due weekly
on Tuesdays (except this one)
 Specific readings already posted will be
augmented but not deleted

7/21/2015
Biochemistry: Introduction
p. 46 of 51
Lateness?

Regular homework:
– No penalty if turned in by 24 h of deadline
– Modest penalties if 1-7 days late
– After 7 days the answer key will be posted, so no
credit given after that

Literature assignments:
– No penalty if turned in by 24 h of deadline
– Half credit if turned in 1-7 days late
– No credit later than that
7/21/2015
Biochemistry: Introduction
p. 47 of 51
Arrangements for exams

Live students should take the exams on the
stated dates—Thursday 9/23 and Tuesday
10/26
 Internet & TV students should begin the
midterms between 9am on the statutory
Thursday and 5pm on Friday
 If you’re a non-local Internet student, you
need to find a proctor well before 23 Sep!
7/21/2015
Biochemistry: Introduction
p. 48 of 51
How exams work

Combination of multiple-choice, short answer,
paragraph-answer, and computational
problems
 No electronic devices of any kind allowed
(you may need to review long division!)
 Multiple-page help sheet will be available for
each exam; in fact, the current drafts of the
help-sheets are already on Blackboard
7/21/2015
Biochemistry: Introduction
p. 49 of 51
Other administrative stuff
We may be moving to the Idea Shop so
that you can use iPads down there
 I’ll tell you that by Thursday’s class
 Feel free to watch the Internet lectures
even if you’re in the live class
 But if you’re in the live section, I expect
you to attend class

7/21/2015
Biochemistry: Introduction
p. 50 of 51