Cells and molecules in cells

The three major divisions (domains) of the living world

Procaryotes and Eukaryotes
Cells contain four major families of small organic molecules
They form the monomeric building blocks, or subunits, for most of the
macromolecules and other assemblies of the cell. Some, such as the
sugars and the fatty acids, are also energy sources.
Sugars are energy sources for cells and
subunits of Polysaccharides
The simplest sugars-the monosaccharides-are compounds with the
general formula (CH
2
O)
n
, where n is usually 3, 4, 5, 6, 7, or 8.
Sugars, and the molecules made from them, are also called
carbohydrates because of this simple formula. Glucose, for
example, has the formula C
6
H
12
0
6
Monosaccharides can be linked by covalent
bonds to form larger carbonhydrates
Two monosaccharides linked
together make a disaccharide.
Three common disaccharides are:
Maltose (glucose + glucose)
Lactose (galactose + glucose)
Sucrose (glucose + fructose)
Larger sugar polymers range from the oligosaccharides
(trisaccharides, tetrasaccharides, and so on) up to giant
polysaccharides, which can contain thousands of monosaccharide
units.
Fatty acids are components of cell memberanes
A fatty acid molecule, such as palmitic
acid (left figure), has two chemically
distinct regions. One is a long
hydrocarbon chain, which is hydrophobic
and not very reactive chemically. The
other is a carboxyl (-COOH) group, which
behaves as an acid (carboxylic acid): it is
ionized in solution (-COO-), extremely
hydrophilic, and chemically reactive.
Almost all the fatty acid molecules in a
cell are covalently linked to other
molecules by their carboxylic acid group.
Unsaturated and Saturated Fatty acids
Phospholipids aggregate to form cell membrannes
The membrane-forming property of phospholipids results from their amphiphilic
nature. Phospholipids will spread over the surface of water to form a monolayer of
phospholipid molecules, with the hydrophobic tails facing the air and the
hydrophilic heads in contact with the water. Two such molecular layers can readily
combine tail-to-tail in water to make a phospholipid sandwich, or lipid bilayer.
This bilayer is the structural basis of all cell membranes
Amino acids are the subunits of proteins
- Amino acids are a varied class of molecules with one defining property:
they all possess a carboxylic acid group and an amino group, both linked
to a single carbon atom called the -carbon. Their chemical variety
comes from the side chain that is also attached to the -carbon.
- Cells use amino acids to build proteins, which are polymers of amino
acids joined head-to-tail in a long chain that is then folded into a three
dimensional structure unique to each type of protein.
Proteins are held together by peptide bonds
Nucleotides are subunits of DNA and RNA
Naming Bases, Nucleosides, Nucleotides
ATP serves as an energy carrier in cells
ATP is formed through reactions that are driven by the energy released by the
oxidative breakdown of foodstuffs. Its three phosphates are linked in series by
two phosphoanhydride bonds, whose rupture releases large amounts of useful
energy. The terminal phosphate group in particular is frequently split off by
hydrolysis, often transferring a phosphate to other molecules and releasing
energy that drives energy-requiring biosynthetic reactions
A small part of one chain of a
deoxyribonucleic acid (DNA) molecule
- Phosphodiester linkage: the phosphoryl
group between the two nucleotide has one
sugar esterified to it through a 3-hydroxyl
and a second sugar esterified to it through a
5-hydroxyl.
- Phosphodiester linkages create the repeating,
that is sugar-phosphate backbone of the
polynucleotide chain.
- DNA chains have a free 5-phosphate at one
end and free 3-hydroxyl at the other end.
Macromolecules are abundant in cell
Macromolecules are made from monomeric subunits
The macromolecules in cells are polymers that are constructed by
covalently linking small organic molecules (called monomers)
into long chains
Noncovalent bonds specify the precise shape of a macromolecule
Noncovalent bonds allow a macromolecule to bind other
selected molecules
Small molecules join together to form macromolecule, which can
assemble into large macromolecular complexes
Protein structure and function
Amino acids are linked together by peptide bonds
Protein are made of polypeptide backnone with
attached side chains
Twenty different amino acids are found in proteins
Torsion angle of a peptide backbone
Phi ()torsion angle: The angle of the N-C bond to the adjacent
peptide bond
Psi ()torsion angle: The angle of the C-C bond to the adjacent
peptide bond
Three types of noncovalent bonds help protein fold
Four levels of protein structure
Helix
An a helix is generated when a single polypeptide chain twists around on
itself to form a rigid cylinder. A hydrogen bond forms between every fourth
peptide bond, linking the C=O of one peptide bond to the N-H of another.
This gives rise to a regular helix with a complete turn every 3.6 amino acids
Parameters of helical peptide structures
Conformation Phi Psi Omega Number of
residues per turn
Distance between
monomers ()
Alpha helix -57 -47 180 3.6 1.5
3-10 helix -49 -26 180 3.0 2.0
Pi-helix 57 -70 180 4.4 1.15
Polyproline I -83 158 0 3.33 1.9
Polyproline II -78 149 180 3.0 3.12
Polyproline helices
Collagen triple helix
Intertwined -helices can form a coiled-coil
Sheet
Beta sheet come in two varieties:
Parallel -sheet and Antiparallel -sheet
Parameters of -sheet structures
Conformation Phi Psi Number of
residues per turn
Distance between
monomers ()
Parallel -sheet -119 113 (2) 3.25
Antiparallel -sheet -139 135 (2) 3.47
Proteins is come in variety of shape and size
Proteins is come in variety of shape and size
Quaternary structure:
The subunit structure of a protein
All proteins bind to other molecules:
The binding of a protein to another molecule is highly selective
Binding sites allow a protein to interact with specific ligand
Enzymes are powerful and highly specific catalysts
Enzymes are remarkable molecules that determine all the chemical
transformations that make and break covalent bonds in cells. They
bind to one or more ligands, called substrates, and convert them
into one or more chemically modified products
Some common types of enzymes
History of Molecular Genetics
Mendels discoveries
Gregor Mendel
(1822-1884)
The discovery of the basic rules of heredity
The concepts were first proposed by Gregor Mendel in 1865 in a
paper entitled Experiments on Plant Hybrids given to the Nature
Science Society at Brno (Czech Republic)
The key to Mendels triumph: genetic variation in pea plants
Mendels experiments
Mendels experiments
Mendels first law: Independent Segregation
-The traits that appears in the F1 progeny is called
dominant, whereas the traits that does not appear in F1
is called recessive.
- F2 generation (3 dominant : 1 recessive).
- The various traits are controled by pairs of factors
(which we now call genes).
-The different forms of a gene (R and r in this case) are
called alleles
- The term homozygous refers to a gene pairs which
have two copies of the same allele (RR or rr).
- The term heterozygous refers to a gene pairs which
have two different alleles (Rr).
- The physical appearance of an organism is its
phenotype.
- The genetic composition of an organism is its
genotype.

*** The appearance of the recessive in F2 indicates that
recessive alleles are neither modified nor lost in F1, but
that the dominant and recessive genes are independently
transmitted and so are able to segregate independently
during the formation of sex cells
Some alleles are neither dominant nor recessive
AA
Aa
aa
AA Aa Aa aa
The inheritance of flower color
in the snapgragon
- Incomplete dominance follows Mendels law
- Heterozygous phenotype (F1) is intermediate
between the two heterozygous phenotype
- Mendels law do not depend on whether one
allele of a gene pair is dominant over the other
Mendels second law: Independent Assortment
- Breeding experiments to peas differing by two
characteristics: round yellow seed x wrinkled
green seeds
- F1: only round yellow seeds
- F2: In addition to the two original phenotypes,
two new types (recombinants) emerged:
wrinkled yellow and round green. Four different
phenotypes appeared in the F2 in a ratio of about
9:3:3:1.
- Alleles of different genes assort independently
of one another during gamete formation. That is,
the segregation of the alleles of gene R is
independent of the segregation of the alleles of
gene Y Independent Assortment
Chromosomal theory of heredity
Walter S. Sutton (1877-1916)
- Suttons paper in 1903: The
Chromosome in Heredity
- The diploid chromosome group
consists of two morphologically similar
sets and during meiosis every gamete
receives only one chromosome of each
homologous pair.
- Explain Mendels result: genes are
parts of the chromosome
Some of the most common single-gene traits in human
Huntington disease: a rare dominant trait
Cystic fibrosis: a recessive condition
Thomas Hunt Morgan (1866-1945)
Gene Linkage
-Two genes do not assort independently if they are located on the same chromosome.
(Genes on the same chromosome are linked)
- In 1908, Thomas Hunt Morgan and his colleagues found mutant in fly (Dorosophila
melanogaster): the gene leading to red eyes (wild-type gene); the gene leading to white
eyes (mutant gene)
The inheritance of a sex-link gene in Drosophila
-When a homozygous red-eye female was
crossed with white-eye male, all the sons and
daughters had red eyes, because red is
dominant over white and all the progeny
had inherited a wild-type X chromosome
from their mother
- When a homozygous white-eye female was
crossed with red-eye male, all the son was
white-eyes and all the daughter was red-
eyes. In this case, the sons inherited X
chromosome from white-eyes mother; Y
chromosome from father does not carry
the eye color locus. The daughters got an X
chromosome bearing white allele from
mother and an X chromosome bearing red
allele from father. The daughter was
therefore red-eye heterozygotes.
- When heterozygous females was mated
with red-eye males, half their sons had white
eyes, but all their daughters had red eyes.
*** Eye color was carried on the X
chromosome, not Y chromosome
In human: colorblindness and two forms of
hemophilia are X-link traits
Crossing Over
Belgian cytologist
Janssens F. A.
(1863-1924)
Janssenss hypothesis of crossing over (1909):
- At the start of meiosis, through the process of
synapsis, the holologous chromosome form pairs
with their long axes paralellel.
- Two of the chromatids break at a corresponding
place on each, then rejoin crossways
- In this manner, recombinant chromatids might be
produced that contain a segment derived from each of
the original homologous chromosome.
Demonstration of physical exchanges between
homologous chromosomes
-The hypothesis that chromosomes
physically interchange material during
synapsis was proved by Barbara
McClintock and Harriet B. Creighton
(Cornell University) in 1931 with the
corn plant Zea may.

-The two members of a chromosome
pair are not identical: one is marked by
the presence of extra-chromosomal
material of knob-like structure.

- The homozgous c, wx progeny had to
arise by crossing over between C and
wx loci.

Chromosome mapping
Thomas Hunt Morgan and his students had exploited the implication of Janssenss
hypothesis to produce a genetic map (in 1915):
*** Genes located close together on a chromosome would assort with one another
much more regularly (close linkage) than genes located far apart on a chromosome.
- Consider the segregation of three genes (A, B, C or a, b, c) all located on the same
chromosome
Cross between
AB and ab
Cross between
AC and ac
Cross between
BC and bc
Parental combinations AB and ab AC and ac BC and bc
Recombinants Ab and aB (30%) Ac and aC (10%) Bc and bC (25%)
*** Genes a and c are close together than a and b or b and c. The gene arrangement
that best fit these data is a-c-b
Chromosome mapping
The use of three-factor crosses to assign gene order: ABC x abc
- Six recombinants: Acb and aCB (7.5%), ACb and acB (22.5%), AcB and aCb (2.5%)
-The least frequent pair of recombinants must arise from a double crossover.
- The gene arrangement that best fit these data is a-c-b
Genetic map of chromosome of Dorosophila
(Morgans lab, 1915)
Thomas Hunt Morgan and his students had assigned locations for more than 85 mutant
genes in Drosophila, placing them at distinct spots on one of the four linkage groups,
or chromosomes.
*** All genes on a given chromosme were located on a line. The gene arrangement
was strictly linear and never branched
Distances between genes on map: map units
Map distance = 100 x recombinant frequency
= 100 x 0,17 = 17 cM (centimorgan)
Summary 1
1865: Hereditary factors were first discovered and described by
Mendel. The gene was recognized as a particulate factors that
pass unchanged from parent to progeny. A gene may exist in
alternative forms (alleles)
1903: Chromosome are hereditary units (Suttons paper)
1908 -1910: Genes lie on chromosomes. Gene linkage (Morgan
et al.)
1909: Janssenss hypothesis of crossing over
1913: Chromosome contains linear arrays of genes. The genetic
map of Drosophila (Morgan et al.)
1931: Recombination is caused by crossing over (McClintock
and Creighton)
DNA is the Genetic Material
Frederick Griffith (1879-1941)
English microbiologist
Discovery of Transformation
Bacterial cell (Streptococus pneumoniae)
- The virulence of the bacterium is determined
by its capsular polysaccharide.
- Smooth bacteria strain (S strain): has
capsular polysaccharide (virulent/ pathogenic)
- Rough bacteria strain (R strain): No capsular
polysaccharide (avirulent/ nonpathogenic)
Discovery of Transformation:
Griffiths experiments in 1928
Pneumonococcus type
Infection of mice
Transformation of a genetic characteristic of a
bacteria cell (Streptococcus pneumoniae)
When pathogenic cells are killed by heat, their genetic components remain
undamaged. These components can pass through the cell wall of the living
recipients cells and undergo subsequent genetic recombination with the
recipients genetic apparatus.
Oswald T. Avery (1877-1955)
US microbiologist
The transforming principle is DNA:
Oswald T. Averys experiments in 1944
T2 Bacteriophage
Viral genes are also nucleic acids
The genetic material of phage T2 is DNA:
Hershey - Chases experiments in 1952
Alfred D. Hershey and Martha Chase
(Cold Spring Harbor Laboratory)
- Parental phage: the protein coat was labeled with the
radioactive isotope 35S, the DNA core was labeled with the
radioactive isotope 32P
- Progeny phage: much of parental DNA (32P) and none of
parental protein (35S) was detected
*** Only the DNA component of T2 carries the genetic
information
The chemical composition of DNA
Erwin Chargaff
(1905-2002)
Analysis of nucleotide composition of DNA
(Chargaffs experiments, 1949)
Chargaffs rules
The X-ray analysis of DNA structure
Rosalind Franklin (1920-1958)
Kings College, London
Franklins X-ray diffraction
photograph of DNA, 1953
Maurice Wilkins
(1916-2004)
DNA is double helix: Watson-Crick model (1953)
James D. Watson and Francis H. Crick
(1953)
The double-helical structure of DNA
was built based on Chargaffs rules
and Franklin and Wilkins X-ray
diffraction studies.
The key features of DNA structure
Complementary base pairing:
- G pairs with C by forming three hydrogen
bonds
- A pairs with T by forming two hydrogen
bonds
- Every base pair consists of one purine (G
or A) and one pyrimidine (C or T)
- It is a double-stranded helix
- It has a uniform diameter
- It is right-handed (It twists to the right)
- It is antiparallel (the two strand run in opposite
directions)
- The sugar-phosphate backbones of the
polynucleotide chains coil around the outside of
the helix, and the nitrogenous bases point toward
the center
James D. Watson and Francis H. Crick Maurice Wilkins
Nobel Prize 1962:
Determination of the structure of DNA
US biochemist Arthur Kornberg
(1918-2007)
Nobel Prize in Physiology or
medicine 1959
Finding the polymerase that make DNA
(Kornbergs research, 1956)
DNA can be synthesized in a test-tube (in vitro)
system with three substances:
-The nucleotide building blocks for DNA are
energy-rich precursor deoxyribonucleoside
triphosphates (dATP, dGTP, dCTP, and dTTP)
- The enzyme DNA polymerase, that was capable of
catalyzing the synthesis of new DNA strands
- DNA, which serves as a template to guide the
incoming nucleotides.

DNA is the direct template for its own formation
(Kornbergs research, 1956)
Three models for DNA replication
Semiconservative replication, in which each
parent strand serves as a template for a new
strand, and the two new DNAs each have one
old and one new strand
Conservative replication, in which the
original double helix serves as a template for,
but does not contribute to a new double helix
Dispersive replication, in which fragments
of the original DNA serves as a template for
assembling two new DNAs, each containing
old and new parts, perhaps at random
Three models for DNA replication
Experimental proof of semiconservative replication
(The Meselson-Stahl experiment, 1958)
The central dogma
The flow of genetic information
Establishing the genetic code
Completion of the code in 1966 revealed that 61 out of the
64 possible permuted groups corresponded to amino acids
Summary 2
Discovery of Transformation (Griffiths experiments in 1928)
The transforming principle is DNA (Averys experiments in 1944)
The genetic material of phage T2 is DNA (Hershey - Chases
experiments in 1952)
Analysis of nucleotide composition of DNA (Chargaffs rules, 1949)
The X-ray analysis of DNA structure (Franklin and Wilkinss X-ray
diffraction studies, 1953)
A double-helical structure of DNA was proposed by Watson and
Crick, 1953
Finding the polymerase that make DNA (Kornbergs research, 1956)
Experimental proof of semiconservative DNA replication (Meselson-
Stahl experiment, 1958)
According to the central dogma information flows from DNA to
RNA to protein