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CHAPTER 2
The Chemical Basis of Life
Introduction
• Understanding cellular function requires knowledge of structure.
• Structure and function in cells is closely related to the structure of molecules and atoms.
• The study of chemistry is essential for understanding cell biology.
2.1 Covalent Bonds (1)
• Bonds between atoms with shared pairs of electrons are called covalent bonds.– Molecules are stable
combinations of atoms held together by covalent bonds.
– Compounds are molecules with more than one type of atom.
Covalent Bonds (2)
• Atoms tend fill their outer electron shell by sharing electrons with other atoms.– Hydrogen forms a single covalent bond by
sharing its unpaired electron.– Oxygen forms two covalent bonds by sharing
two unpaired electrons.– Water results when oxygen bonds with two
hydrogens.
Covalent Bonds (3)
• It requires 80-100 kilocalories to break a mole of covalent bonds.
• Multiple bonds are formed when more than one pair of electrons are shared by two atoms.
• Shared electrons stay closest to the nucleus with the highest electronegativity.– Depends upon the number of protons in nucleus.– Depends upon the distance of the shard electrons
from the nucleus.
Covalent Bonds (4)
• Polar and Nonpolar Molecules– Polar molecules have asymmetric
distributions of electrical charge.– Nonpolar molecules lack polarized bonds.– Some biological molecules, such as proteins
and phospholipids, have both polar and nonpolar regions.
Covalent Bonds (5)
• Ionization– Ions result when strongly electronegative
nuclei capture electrons.– Anions have extra electrons.– Cations have lost electrons.– Free radicals are unstable atoms or
molecules with unpaired electrons.
The Human Perspective: Free Radicals as a Cause of Aging (1)
• Free radicals are atoms or molecules with an unpaired electron.– They are formed during normal metabolism.– Are highly reactive and damage
macromolecules such as DNA.– May play a role in aging.
The Human Perspective: Free Radicals as a Cause of Aging (2)
• Superoxide dismutase (SOD) is an enzyme that destroys the superoxide radical (O2
.–).
– SOD protects cells from damage due to the superoxide radical.
– SOD extends the life span of laboratory animals that overproduce it.
The Human Perspective: Free Radicals as a Cause of Aging (3)
• Calorie restriction:– Extends the lifespan of experimental
animals.– Results in decreased production of free
radicals.– A new study indicates that individuals on a
diet containing 25% fewer calories show reduced levels of DNA damage.
2.2 Noncovalent Bonds (1)
• Noncovalent bonds are attractive forces that are weaker than covalent bonds.
• Weak bonds are broken and re-formed.
• Weak bonds play an important role in dynamic cellular processes.
Noncovalent Bonds (2)
• Types of noncovalent bonds– 1. Ionic bonds –
attractions between charged atoms.
• Are weakened in the presence of water.
• They may be significant within large biological molecules.
Noncovalent ionic bonds
Noncovalent Bonds (3)
2. Hydrogen bonds:-- A hydrogen bond occurs when covalently bound hydrogen has a partial positive charge and attracts electrons of a second atom.-- H-bonds determine the structure and properties of water.-- H-bonds occur in biological molecules, such as between the strands of DNA.
Hydrogen bonds
Noncovalent Bonds (4)
3. Hydrophobic interaction and van de Waals forces:
- These occur when nonpolar molecules associate and minimize their exposure to polar molecules.
- van der Waals forces, or attractions between nonpolar molecules, are due to transient dipole formation.
Noncovalent Bonds (5)
• The Life-Supporting Properties of Water– The structure of water
is suitable for sustaining life.
• It is asymmetric – both H atoms are on one side.
• Both covalent O–H bonds are highly polarized.
• All three atoms readily form H-bonds.
Noncovalent Bonds (6)
• The Life-Supporting Properties of Water– The properties of water result from its
structure.• It is asymmetric—both H atoms are on one side.• It requires a lot heat to evaporate it.• It is an excellent solvent for many substances.• It determines the interactions between many
biological solutes.
The importance of water in protein structure
2.3 Acids, Bases, and Buffers (1)
• Acids release protons.
• Bases accept protons.
• Amphoteric molecules can act as either acids or bases. For example, water:
H3O ↔ H+ + H2O ↔ OH– + H+
Acid Amphoteric Base
molecule
Acids, Bases, and Buffers (2)
• Acidity is measure using the pH scale.– pH = –log [H+]– The ion product constant for water is
Kw = [H+][OH–] = 10-14 at 25 °C.
– As [H+] increases, then [OH-] decreases so that the product equals 10–14.
• Biological processes are sensitive to pH.– Changes in pH affect the ion state and
function of proteins.– Buffers in living systems resist changes in
pH.– For example, bicarbonate ions and carbonic
acid buffer the blood:
HCO3– + H+ ↔ H2CO3
Bicarbonate Hydrogen Carbonic
ion ion acid
Acids, Bases, and Buffers (3)
2.4 The Nature of Biological Molecules (1)
• Carbon is central to the chemistry of life.– Carbon forms four covalent bonds, with itself
or other atoms.– Carbon-containing molecules produced by
living organisms are called biochemicals.
The Nature of Biological Molecules (2)
• Carbon is central to the chemistry of life– Hydrocarbons:
• Contain only carbon and hydrogen.
• Vary in the number of carbons, and the number of double and triple bonds between carbons.
The Nature of Biological Molecules (3)
• Functional groups—groups of atoms giving organic molecules different characteristics and properties.
• Functional classification of biological molecules:Macromolecules: large structural and functional molecules in cells. Include four major categories: proteins, nucleic acids, polysaccharides and lipids.
The Nature of Biological Molecules (4)
• Building blocks of macromolecules include amino acids, nucleotides, sugars, and fatty acids.
• Metabolic intermediates: compounds formed in metabolic pathways.
• Molecules of miscellaneous function: include vitamins, hormones, ATP, and metabolic waste products.
Monomers and polymers
2.5 Four Types of Biological Molecules (1)
Four Types of Biological Molecules (2)
• Carbohydrates include simple sugars and sugar polymers.– They serve as energy storage molecules.– Structure:
• Chemical formula is (CH2O)n
• Ketose sugars have a carbonyl (C=O) on an internal carbon
• Aldose sugars have a carbonyl on a terminal carbon.
• Sugars can be linear but sometimes form ring structures.
The structures of sugars
Four Types of Biological Molecules (3)
• Carbohydrates– Stereoisomerism:
• Asymmetric carbons bond to four different groups.• Molecules with asymmetric carbons can exist in
two mirror-image configurations called enantiomers or stereoisomers.
• Enantiomers can be as either D- or L-isomers.• Sugars can have many asymmetric carbons, but
are designated D- or L- according to the arrangement around the carbon farthest from the carbonyl group.
Stereoisomerism
Four Types of Biological Molecules (4)
• Carbohydrates– Linking Sugars
Together:• Glycosidic bonds are
–C—O—C– links between sugars.
• Disaccharides are used as a source of readily available energy.
• Oligosaccharides are found bound to cells surface proteins and lipids, and may be used for cell recognition.
Four Types of Biological Molecules (5)
• Carbohydrates– Polysaccharides are
polymers of sugars joined by glycosidic bonds.
• Glycogen is an animal product made of branched glucose polymers.
• Starch is a plant product made of both branched and unbranched glucose polymers.
Four Types of Biological Molecules (6)
• Cellulose, chitin, and glycosaminoglycans (GAGs): structural polysaccharides– Cellulose: plant product
made of unbranched polymers
– Chitin: component of invertebrate exoskeleton made
– GAGs: composed of two different sugars and found in extracellular space.
Four Types of Biological Molecules (7)
• Lipids are a diverse group of nonpolar molecules.– Fats are made of glycerol linked by three
ester bonds to three fatty acids (Fas).• FAs are unbranched hydrocarbons with one
carboxyl group; they are amphipathic.• Saturated FAs lack C=C double bonds and are
solid at room temperature.• Unsaturated FAs have one or more C=C double
bonds and are liquid at room temperature.
Fats and fatty acids
Fats and fatty acids
Four Types of Biological Molecules (8)
• Steroids are four-ringed animal lipids that have been implicated in atherosclerosis.
• Phospholipids are amphipathic lipids that are a major component of cell membranes.
Four Types of Biological Molecules (9)
• Proteins are polymers of amino acids and form a diverse group of macromolecules.– They exhibit a high
degree of specificity.– They have a variety
of cellular functions.
Four Types of Biological Molecules (10)
• The Building Blocks of Proteins– Amino acids have an α carbon, an amine
group, a carboxyl group, and a variable R group.
– Amino acids in nature occurs as the L stereosisomer.
– Amino acids are linked together by peptide bonds into a polypeptide chain to make a protein.
Amino acid structure
Four Types of Biological Molecules (11)
• Peptide bonds form between the α-carbonyl and the α-amino of participating amino acids.
• Amino acids differ in the R group attached to one of the bonds of the α-carbon.– R groups may be polar charged.– R groups may be polar uncharged.– R groups may be nonpolar.
The chemical structures of amino acids
The chemical structures of amino acids
Four Types of Biological Molecules (12)
• R groups may have other properties.– Glycine has only –H as its R group and is
small.– The α-carbon of proline is part of a ring,
creating kinks in the protein.– Cysteine forms disulfide bridges (—SS—)
with other cysteines.– The nature of the R groups determines the
function of the protein.
Hydrophobic and hydrophilic amino acid residues in the protein cytochrome c
Four Types of Biological Molecules (13)
• The Structure of Proteins– Primary structure, the sequence of amino
acids in the polymer, is critical to the protein function.
– Secondary structure refers to the conformation of adjacent amino acids into α-helix, β-sheet, hinges, turns, turns, loops, or finger-like extensions.
Secondary structure of proteins
Secondary structure of proteins
Four Types of Biological Molecules (14)
• Tertiary structure is the conformation of the entire polymer.– It is stabilized by
noncovalent bonds.– It is studied by X-
ray crystallography.
– Proteins can be fibrous or globular.
Types of noncovalent bonds maintaining the conformation of proteins
Four Types of Biological Molecules (15)
• Myoglobin: The First Globular Proteins Whose Tertiary Structure Was Determined– Stores oxygen in
muscle cells.– Has a heme prosthetic
group that binds O2.
– Structure derived using X-ray crystallography.
Four Types of Biological Molecules (16)
• Protein Domains– Domains occur when
proteins are composed of two or more distinct regions.
– Each domain is a functional region
Four Types of Biological Molecules (17)
• Dynamic Changes within Proteins– May occur with protein
activity.– Conformational
changes are non-random movements triggered by the binding of a specific molecule.
Four Types of Biological Molecules (18)
• Quaternary structure refers to proteins composed of subunits.– It refers to the manner
in which subunits interact.
Four Types of Biological Molecules (19)
• Protein-Protein Interactions– Different proteins can become physically
associated to form a multiprotein complex.
Four Types of Biological Molecules (20)
• Protein-Protein Interactions– Can be studied
using the yeast two-hybrid (Y2H).
– The Y2H is an indirect assay and includes lots of uncertainties.
Four Types of Biological Molecules (21)
• Protein-Protein Interactions– Results from large-
scale studies can be presented in the form of a network.
– A list of potential interactions can be elucidate unknown processes.
Four Types of Biological Molecules (22)
• Protein Folding is a process that occurs in various steps.– Anfinsen observed
that unfolding is due to denaturation, brought about by various agents.
– Removal of denaturing agents could lead to refolding.
Four Types of Biological Molecules (23)
• Two alternate pathways for protein folding:– Proteins may assume their native
conformation through a series of steps.– Proteins may fold along pathways without
intermediate forms.– Smaller proteins with single domains fold
faster than larger proteins with multiple domains.
Two alternate pathways for protein folding
Four Types of Biological Molecules (24)
• The Role of Molecular Chaperones– Molecular chaperones are “helper proteins”
to prevent nonselective interactions during protein folding.
• Hsp 70 family bind emerging proteins and prevent inappropriate interactions.
• Chaperonins allow large new proteins to assemble without interference from other macromolecules.
The role of molecular chaperones in encouraging protein folding
The Human Perspective: Protein Misfolding Can Have Deadly Consequences (1)
• Creutzfeld-Jakob Disease (CJD) results from misfolded protein in the brain.– Healthy brains contain a normal protein, PrPc.– CJD brains have PrPSc, which is identical or
similar to PrPc but is misfolded.– “Mad cow disease”, kuru, and sccrapie are
also caused by PrPSc.
A contrast in structure
The Human Perspective: Protein Misfolding Can Have Deadly Consequences (2)
• Alzheimer’s disease (AD) involves misfolded proteins that accumulate in the brains of affected individuals.– A membrane-bound protein in brain neurons, called
amyloid precursor protein (APP), is cleaved by two secretase enzymes.
– In individuals genetically predisposed to AD one of the cleavage products is Aβ42, a protein that misfolds and self-associates into amyloid plaques.
Alzheimer’s disease
The Human Perspective: Protein Misfolding Can Have Deadly Consequences (3)
• All drugs for treatment of AD are aimed at management of symptoms.
• Pursuit of new drugs for AD aimed at:– Prevent formation of Aβ42 peptide.– Remove the Aβ42 peptide once it has formed.– Prevent interaction between Aβ molecules.
Formation of the Aβ peptide
Four Types of Biological Molecules (25)
• The Emerging Field of Proteomics– The proteome is the entire inventory of an
organism’s proteins.– Proteomics uses advanced technologies to
perform large-scale studies on diverse proteins.
• Proteins are separated using gel electrophoresis.• Proteins are identified using mass spectrometry
and high speed computers.
The study of proteomics often requires the separation of complex mixtures of proteins
Identifying proteins by mass spectrometry
Four Types of Biological Molecules (26)
• The Emerging Field of Proteomics– Protein microarrays (protein chips) allow
researchers to screen proteins for various activities and disorders.
– In a near future biotechnology companies will be manufacturing microarrays containing antibodies for different blood proteins, which may indicate that a person may be suffering from a particular disease.
Global analysis of protein activities using protein chips
Four Types of Biological Molecules (27)
• Protein Engineering– Current technology allows the making of artificial
genes that code for proteins of specific amino acids sequences.
– Knowledge of a protein’s amino acid sequence rarely allows prediction of a protein’s structure.
– Site-directed mutagenesis allows researchers to make alterations in single amino acids by altering the DNA encoding a protein.
Four Types of Biological Molecules (28)
• Structure-Based Drug Design– Computer simulations of protein binding sites
are used to design drugs that inhibit specific proteins.
– An example of such application is the drug Gleevec for treatment of rare cancers.
Development of a protein-targeting drug
Four Types of Biological Molecules (29)
• Protein Adaptation and Evolution– Adaptations are traits that improve the chance
of survival of an organism in a specific environment.
– Proteins are subject to natural selection.– Members of a protein family are thought to
have evolved from a single ancestor gene.– A particular protein may have different
versions (isoforms) that are tissue- or stage-specific.
Distribution of polar, charged amino acid residues in the enzyme malate
dehydrogenase
Four Types of Biological Molecules (30)
• Nucleic acids are polymers of nucleotides that store and transmit genetic information.– Deoxyribonucleic acid (DNA) holds the genetic
information in all cellular organisms and some viruses.
– Ribonucleic acid (RNA) is the genetic material in some viruses.
– Nucleotides are connected by 3’-5’ phosphodiester bonds between the phosphate of one nucleotide and the 3’ carbon of the next.
Nucleotides and nucleotide strands of RNA
Four Types of Biological Molecules (31)
• Each nucleotide consists of three parts:– A five-carbon sugar– A phosphate group– A nitrogenous base
• Bases are either purines or pyrimidines.• The purines are adenine and guanine in both
DNA and RNA.• The pyrimidines are cytosine and uracil in RNA;
uracil is replaced by thymine in DNA.
Nitrogenous bases in nucleic acids
Four Types of Biological Molecules (32)
• RNA is usually single stranded and DNA is usually double stranded.– RNA may fold back on itself to form complex three
dimensional structures, as in ribosomes.– RNA may have catalytic activity; such RNA enzymes
are called ribozymes.– Adenosine triphosphate (ATP) is a nucleotide that
plays a key role in cellular metabolism, whereas guanosine triphosphate (GTP) serves as a switch to turn on some proteins.
RNA and the ribosome
RNA and the ribosome
2.6 The Formation of Complex Molecular Structure
• Different types of subunits can self-assemble to form complex structures.
• One example is the tobacco mosaic virus (TMV), which was shown to self-assemble from ribosomal subunits and proteins.
• Cells may use molecular chaperones to assemble molecular structures.
Experimental Pathways: Helping Proteins Reach Their Proper Folded State (1)
• Some proteins can self-assemble from purified subunits.
• Other proteins require molecular chaperones for proper folding.– Molecular chaperones may protect protein
structure during the heat shock response.– The heat shock response involves synthesis
of heat shock proteins that prevent denaturation of existing proteins.
Experimental Pathways: Helping Proteins Reach Their Proper Folded State (2)
• Heat shock proteins and other chaperones prevent aggregation of denatured or newly synthesized proteins.
• Chaperones also move newly synthesized proteins across membranes.
• The protein GroEL is synthesized in E. coli is essential for the proper folding of other cellular proteins.
GroEL
Experimental Pathways: Helping Proteins Reach Their Proper Folded State (3)
• GroEl acts in conjunction with another protein, GroES.
• Attachment of GroES to GroEL induces a conformational change in the GroEL protein.
• The GroEL-GroES complex assists a protein and achieving its native state.
GroEL-GroES-assisted folding of a polypeptide