BIO 203 Biochemistry I

by
Seyhun YURDUGÜL, Ph.D.

Lecture 1
What is Biochemistry?
Historical and Cellular Aspects
 Content Outline
• Definition
• The origin of life concept
• From simple to complex
• Macroelements and microelements
• Energy transformation
• Discoveries: Urea
• Discoveries: DNA and RNA
 Other definitions
• The chemistry of biology;
• the application of the tools and concepts of
chemistry to living systems.
• Biochemist(s): study the structures and
physical properties of biological molecules
 Other definitions
• The chemistry of living things,
• including the structure and function of
biological molecules and the mechanism
and products of their reactions.
 Most appropriate definition
• Biochemistry is the chemistry of life.
Biochemists study the elements, compounds
and chemical reactions that are controlled
by enzymes and take place in all living
organisms.

(Definition of Wikipedia Encyclopedia)

Structure of DNA
 The origin of life consists
biochemistry
• How can life be detected regardless of its
nature and origin?
• the first sign of life elsewhere:
spectroscopic detection of co-occurring
nonequilibrium gases:
 The origin of life consists
biochemistry
For instance:
oxygen and methane, in the atmosphere of a
planet around some distant star,
according to the recent spectacular
advances in astronomy.
Molecular Organization of DNA
 The Origin of Life consists
Biochemistry

Co-occurrence of such gases indicate:

 they are replenished,
 perhaps most readily explained by the
influence of life
Life is Everywhere: Microorganisms (Bacteria)
Bordetella spp.
 The Origin of Life consists
Biochemistry
• By observation of oxygen and methane, Earth: as a home
for life even from distant galaxies.

• Other potential habitats for life in this solar system: (Mars

and Europa) however, are not so obvious.

• search life on them: at the level of analytical chemistry.

• the attempts for detection of extraterrestrial life: tell us

where and how to look for life, and the forms it can take.
The basic drive of life is to make
more of itself.
• Chemical reactions required for propagation
of a living organism:
• require high specificity in the interactions
of the molecules for propagation.
• Such specificity requires information, in the
form of complex molecules:
 How these complex molecules are?

• very large, proteins and RNAs with

molecular weights of thousands to millions
of daltons,
• or even larger as DNA.
• prediction: life will be composed of
macromolecules
 Macroelements and microelements
• Macroelements: The essential elements
present in the nature, which composes the
life (C,H,N,O,P,S,Si)
• Only two of the natural atoms, carbon and
silicon: serves as the backbones of
molecules sufficiently large to carry
biological information.
• Carbon: generally has focused as unique
 The Carbon
• For the structural basis for life, one
important feature of C:
• it can readily engage in the formation of
chemical bonds with many other atoms,
• allowing for the chemical versatility
required to conduct the reactions of
biological metabolism and propagation,
unlike silicon.
 Other macroelements
• Play role in the various organic functional
groups(in proteins, aminoacids, sugars and
fats)
• composed of hydrogen,
• oxygen,
• nitrogen,
• phosphorus,
• sulfur
 Microelements
 such as iron,
 potassium
 manganese
 magnesium,
 calcium
 zinc
 iodine etc.
• Trace elements which are required as small amounts which
provide the enormous diversity of chemical reactions
necessarily catalyzed by a living organism.
 How can we build blocks of living
organism?
• By macro and micro-elements.
• Life : builds simple organic molecules that are
used as building blocks for large molecules.
• Amino acids : construct the long chains of
proteins;
• simple sugars combine with purine and pyrimidine
bases and phosphate : to construct the nucleic
acids.
 From Simple to Complex
• It seems logical that the evolution of any
organic-based life form:
• results in the construction of complex
molecules as repeating structures of simple
subunits.
The molecular model of the simplest amino acid: Glycine
The complex structure of proteins
 Building complex blocks require
energy
• Energy transformation is a critical issue.
• processes of life: require the capture of
adequate energy,
• from physical or chemical processes, to
conduct the chemical transformations
required for life.
 Based on thermodynamics
• There are only two such energy-capturing
processes that can support "primary
productivity,"
• the synthesis of biological materials from
inorganic carbon dioxide.
 The two processes
• One process, termed lithotrophy,
• involves the oxidation and concomitant reduction of
geochemical compounds.
• E.g. methanogenic bacteria gain energy for growth by the
use of H2 as high-energy electron source,
• transferred to CO2, forming CH4.
 Lithotropy
• Other microorganisms (m/o) might use H 2S
as an energy source, respiring with O2, to
produce H2SO4.
• It is thought : the earliest life on Earth relied
on lithotrophy.
 Chemotrophy
• The second energy production process
• Organic chemical substances are used for
energy requirement
• i.e. Glucose,
• universal energy source from bacteria to
human body
Glucose, pure
 Chemical setting:Photosynthesis
for chemotrophy
• Photosynthetic organisms require sufficient light of
appropriate frequency.
• The light must be sufficiently energetic to support
biosynthesis, but not so energetic as to be chemically
destructive.
• the spectral zone of about 300-1,500 nm in wavelength.
Chemical setting:Photosynthesis
for chemotrophy
• Terrestrial photosynthesis is limited to
about 400-1,200 nm.
• terrestrial life requires CO2 as a carbon
source, energy pigments and only a few
elements: H, N, P, O, S, and the suite of
metals.
 Physical settings
• Physical constraints on life include
• temperature,
• pressure,
• and volume.
• The extreme diversity of terrestrial life
probably provides an analog for life's
diversity anywhere
 Temperature is a critical factor
for life.
• Temperatures must be sufficiently high that:
• reactions can occur
• but not so high that; complex and relatively
fragile biomolecules are destroyed.
• Moreover, the temperature must be in a
range for water to have the properties
necessary for solute transfer.
 Water and Temperature
• Water can be stabilized against boiling by
pressure,
• but at too-low temperatures, water becomes
crystalline and inconsistent with transport.
• Currently, the upper temperature record for
culturable microbes is 112-113°C,
• held by hyperthermophilic archaeons of the
genera Pyrolobus and Pyrodictium
 Resistant (Extreme) forms to high
temperature:
The bacterial spores
• Even the spectacularly durable bacterial
endospore does not survive extended
heating beyond 120°C.
• The lower-temperature boundary for life is
not established,
• but microbes are recoverable from ice,
• and growth of organisms has been detected
in ice to 20°C.
 Pressure and Volume
• pressure required for life:
• probably limited at the lower end only by vapor
pressure required to maintain water or ice.
• upper limit for pressure tolerance : unknown.
Organisms on terrestrial seafloor experience
pressure over 1,000 atmospheres,
• microbes recovered from deep oil wells are
exposed to far higher pressures.
 Historical milestones of
Biochemistry

• ON THE ARTIFICIAL PRODUCTION OF

UREA
• by F. Wöhler
Annalen der Physik und Chemie, 88,
Leipzig, 1828
 Wöhler:The Father of Biochemistry
• He had originally trained as a physician,
• had isolated urea during an investigation of the
waste products found in urine.
• This captured his imagination, and he decided to
focus on chemistry instead of medicine.
• Wöhler went on to become professor of chemistry
at Gottingen, where he became interested in
substances that could release cyanide when heated.
 Wöhler’s discovery of urea
• One day in 1828, he heated up some ammonium
cyanate, expecting to liberate some cyanide.
• None was released.
• but his original crystals: on a new form.
• their weight had not changed,
• but these crystals had a different melting point and
a different appearance from his starting material.
What could have happened?
 Wöhler’s discovery of urea
• When Wöhler examined the crystals, he
realized that their shape seemed familiar.
• Where had he seen them before?
• His mind dated back to his medical-school
days
• and then he knew: he was looking at
crystals of urea!
 Historical Milestones of
Biochemistry-2
• There seems to be no reference whatsoever
to Dr. Wilhelm Schuessler,
• who discovered the 12 essential mineral
elements of which the body is both
composed and requires for life.
• German Scientist, homoeopath and Medical
Doctor who lived in Oldenburg, Germany
(1821 - 1898)
 Fathers are increasing!!!
• Fischer
• carried out extremely comprehensive work in three
main fields: purines, sugars, and peptides,
• the last two effectively founding biochemistry on
basis of organic chemistry.
• work on purines resulted in the synthesis of many
important compounds, including the alkaloids:
caffeine and theobromine, and purine itself (1898).
 Fischer’s Nobel Prize for chemistry
• In 1899 Fischer turned to amino acids and peptides
• devised a peptide synthesis that eventually produced a
polypeptide of 18 amino acids (1907).
• His other work : the first synthesis of a nucleotide (1914),
• the 'lock-and-key' hypothesis of enzyme action,
• work on tannins, and
• attempts to prepare very high-molecular-weight
compounds.
• was awarded the Nobel: 1902 (on purines and sugars)
 Biochemistry moves rapidly:
Protein Crystallography
• The first records of crystallized
polypeptides or proteins date back to the
late 1920s / early 1930s
• 1926: John Sumner, urease; The first
enzyme discovery    
• 1934: J. D. Bernal and Dorothy Crowfoot-
Hodgkin, pepsin;
• 1935: Crowfoot-Hodgkin, insulin.
 Linus Pauling and Robert Corey
• the first X-ray crystal structures of proteins came
into view,  
• began in the mid-1930s:
• to catalogue bond lengths and angles in amino
acids.
 Linus Pauling and Robert Corey
• By the early 1950s, they had predicted the
two basic structures of amino acid
polymers:
• on the basis of hydrogen bonding patterns:
• as the ‘helices and sheets’.
 Linus Pauling and Robert Corey
• As of 1960, about 75 proteins had been
crystallized,
• and interest began on sequence content to
catalytic activity of these enzymes.
 Hemoglobin structure by X-ray
diffraction
• Earlier (1953), Perutz found:
• a structure could be solved by comparing
the X-ray diffraction pattern of crystals,
• of native hemoglobin with that of
hemoglobin combined with the heavy atom
mercury.
• When this was demonstrated a few years
later, modern structural biology was
founded(and molecular biology little after!)
 X-ray diffraction for protein
structure
• However, only in 1959 did Max Perutz and
John Kendrew:
• succeed in deciphering the X-ray diffraction
pattern:
• from the crystal structure of the
protein(hemoglobin and myoglobin,
respectively).
 DNA and gene’s discovery
• In 1943, American Oswald Avery:
• proved DNA carries genetic information.
• he suggested DNA might actually be the
gene.
 DNA and gene’s discovery
• Most people at the time thought the gene
would be protein,
• not nucleic acid,
• but by the late 1940s,
• DNA was largely accepted as the genetic
molecule.
 Structure of DNA
• In 1948, Linus Pauling :
• many proteins take the shape of an alpha helix,
spiraled like a spring coil.
 Structure of DNA
• In 1950, biochemist Erwin Chargaff :
• arrangement of nitrogen bases in DNA
varied widely,
• but the amount of certain bases always
occurred in a one-to-one ratio.
• These discoveries were an important
foundation for the later description of DNA.
 Watson and Crick
The Real Discoverers of DNA
• In the early 1950s: the race to discover DNA
• At Cambridge University, graduate student
Francis Crick and research fellow James Watson:
• impressed especially by Pauling's work.
 Watson and Crick
The Real Discoverers of DNA
• Cambridge team's approach: to make
physical models to form an accurate picture
of the molecule.
• took an experimental approach, looking
particularly at x-ray diffraction images of
DNA.
 Watson and Crick
The Real Discoverers of DNA
• In 1951, Watson attended a lecture by Franklin on her
work to date.
• She had found that DNA can exist in two forms, depending
on the relative humidity in the surrounding air:
• helped her deduce that the phosphate part of the molecule
was on the outside.
 Watson and Crick
The Real Discoverers of DNA
• Based on this information, Watson and
Crick made a failed model.
• It caused the head of their unit to tell them
to stop DNA research.
• But the subject just kept coming up.
 Watson and Crick
The Real Discoverers of DNA
• Franklin, working mostly alone,
• found that her x-ray diffractions showed
that the "wet" form of DNA (in the higher
humidity) had all the characteristics of a
helix.
 Watson and Crick
The Real Discoverers of DNA
• She found: all DNA was helical but not
announced this finding,
• until she had sufficient evidence on the
other form as well.
 Watson and Crick
The Real Discoverers of DNA
• Wilkins was frustrated.
• In January 1953, he showed Franklin's
results to Watson, apparently without her
knowledge or consent.
• Crick later admitted, "I'm afraid we always
used to adopt -- let's say, a patronizing
attitude towards her."
 Watson and Crick
The Real Discoverers of DNA
• Watson and Crick took a crucial conceptual
step,
• suggesting the molecule was made of two
chains of nucleotides, each in a helix
• as Franklin had found,
• but one going up and the other going down.
 Watson and Crick
The Real Discoverers of DNA
• Crick had added that to the model:
• so that matching base pairs interlocked in
the middle of the double helix
• to keep the distance between the chains
constant
 Watson and Crick
The Real Discoverers of DNA
• Watson and Crick showed that each strand of the
DNA molecule was a template for the other.
• During cell division the two strands separate and
on each strand a new "other half" is built, just like
the one before.
• This way DNA can reproduce itself without
changing its structure -- except for occassional
errors, or mutations.
 Watson and Crick
The Real Discoverers of DNA
• The structure so perfectly fit the
experimental data:
• it was almost immediately accepted.
• DNA's discovery has been called the most
important biological work of the last 100
years,
• and the field it opened may be the scientific
frontier for the next 100.
 Watson and Crick
The Real Discoverers of DNA
• By 1962, when Watson, Crick, and Wilkins won
the Nobel Prize for physiology/medicine:
• Franklin had died.
• The Nobel Prize only goes to living recipients, and
can only be shared among three winners.
• Were she alive, would she have been included in
the prize?
 LITERATURE CITED
• Devlin,T.M. Textbook of Biochemistry with
Clinical Correlations,Fifth Edition,Wiley-Liss
Publications,New York, USA, 2002.
• Lehninger, A. Principles of Biochemistry,
Second edition, Worth Publishers Co., New
York, USA, 1993.
• Matthews, C.K. and van Holde, K.E.,
Biochemistry, Second edition, Benjamin /
Cummings Publishing Company Inc., San
Francisco, 1996.