chapter 2 the chemical basis of life. introduction understanding cellular function requires...

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.


• 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.


• 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


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


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.


• 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.


• 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.


• 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.


• 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


• 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


• 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.


• 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.


• 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.


• 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


• Steroids are four-ringed animal lipids that have been implicated in atherosclerosis.

• Phospholipids are amphipathic lipids that are a major component of cell membranes.


• 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.


• 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


• 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


• 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


• 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


• 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


• 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.


• Protein Domains– Domains occur when

proteins are composed of two or more distinct regions.

– Each domain is a functional region


• Dynamic Changes within Proteins– May occur with protein

activity.– Conformational

changes are non-random movements triggered by the binding of a specific molecule.


• Quaternary structure refers to proteins composed of subunits.– It refers to the manner

in which subunits interact.


• Protein-Protein Interactions– Different proteins can become physically

associated to form a multiprotein complex.


• Protein-Protein Interactions– Can be studied

using the yeast two-hybrid (Y2H).

– The Y2H is an indirect assay and includes lots of uncertainties.


• 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.


• 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.


• 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


• 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


• 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


• 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


• 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


• 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


• 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.


• 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


• 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


• 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


• 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


• 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

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.


• 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 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

chapter 2 the chemical basis of life. introduction understanding cellular function requires...

Documents

oxygen bonds

weak bonds

polarized bonds

multiple bonds

mole of covalent bonds

ionic bonds attractions

unpaired electrons

structure of molecules