Professional Documents
Culture Documents
Unit 2 - Biochemistry of Life: Chapter 4: Carbon and The Molecular Diversity of Life
Unit 2 - Biochemistry of Life: Chapter 4: Carbon and The Molecular Diversity of Life
1
Stanley Miller experiment
4.2 Carbon atoms can form diverse molecules by bonding to four other atoms
Carbon has little tendency to form ionic bonds by losing or gaining 4 electrons to complete its
valence shell.
Carbon usually completes its valence shell by sharing electrons with other atoms in four covalent
bonds, which may include single and double bonds.
The ability of carbon to form four covalent bonds makes large, complex molecules possible.
o When a carbon atom forms covalent bonds with four other atoms, they are arranged at the
corners of an imaginary tetrahedron with bond angles of 109.5°.
o In molecules with multiple carbon atoms, every carbon atom bonded to four other atoms has a
tetrahedral shape.
o When two carbon atoms are joined by a double bond, all bonds around those carbons are in the
same plane as the carbons.
Shape of simple organic molecules
2
In carbon dioxide (CO2), one carbon atom forms two double bonds with two O=C=O
oxygen atoms.
o In the structural formula, , each line represents a pair of shared electrons.
Although CO2 can be classified as either organic or inorganic, its importance
to the living world is clear: CO2 is the source of carbon for all organic
molecules found in organisms.
Urea, CO(NH2)2, is another simple organic molecule in which each atom forms
covalent bonds to complete its valence shell.
3
Isomers are compounds that have the same molecular formula but different structures and, therefore,
different chemical properties.
Structural isomers have the same molecular formula but differ in the covalent arrangement of
atoms.
o Structural isomers may also differ in the location of the double bonds.
Cis-trans isomers have the same covalent partnerships but differ in the spatial arrangement of atoms
around a carbon-carbon double bond.
o The double bond does not allow the atoms to rotate freely around the bond axis.
o Consider a simple molecule with two double-bonded carbons, each of which has an H and an X
attached to it. The arrangement with both Xs on the same side of the double bond is called a cis
isomer; the arrangement with the Xs on opposite sides is called a trans isomer.
Enantiomers are molecules that are mirror images of each other.
Enantiomers are possible when four different atoms or groups of atoms are bonded to an
asymmetric carbon.
o The four groups can be arranged in space in 2 different ways that are mirror images of each
other; They are like left-handed and right-handed versions of the molecule.
o Usually one is biologically active, while the other is inactive.
Even subtle structural differences in two enantiomers may have important functional significance
because of emergent properties from specific arrangements of atoms.
4
These chemical groups may be involved in chemical reactions or may contribute to the shape and
function of the organic molecule in a characteristic way, giving it unique properties.
o As an example, the basic structure of testosterone (a male sex hormone) and estradiol (a female
sex hormone) is the same.
o Both are steroids with four fused carbon rings, but the hormones differ in the chemical groups
attached to the rings.
o As a result, testosterone and estradiol have different shapes, causing them to interact differently
with many targets throughout the body.
In other cases, chemical groups known as functional groups affect molecular function through their
direct involvement in chemical reactions.
Seven chemical groups are most important to the chemistry of life: hydroxyl, carbonyl, carboxyl,
amino, sulfhydryl, phosphate, and methyl groups.
The first six chemical groups are functional groups. They are hydrophilic and increase the solubility
of organic compounds in water.
Methyl groups are not reactive but may serve as important markers on organic molecules.
5
In a hydroxyl group (—OH), a hydrogen atom forms a polar covalent bond with an oxygen atom,
which forms a polar covalent bond to the carbon skeleton.
o Because of these polar covalent bonds, hydroxyl groups increase the solubility of organic
molecules.
o Organic compounds with hydroxyl groups are alcohols, and their names typically end in -ol.
A carbonyl group (>CO) consists of an oxygen atom joined to the carbon skeleton by a double bond.
o If the carbonyl group is on the end of the skeleton, the compound is an aldehyde.
o If the carbonyl group is within the carbon skeleton, the compound is a ketone.
o Isomers with aldehydes and those with ketones have different properties.
A carboxyl group (—COOH) consists of a carbon atom with a double bond to an oxygen atom and a
single bond to the oxygen atom of a hydroxyl group.
o Compounds with carboxyl groups are carboxylic acids.
o A carboxyl group acts as an acid because the combined electronegativities of the two adjacent
oxygen atoms increase the chance of dissociation of hydrogen as an ion (H+).
6
An amino group (—NH2) consists of a nitrogen atom bonded to two hydrogen atoms and the carbon
skeleton.
o Organic compounds with amino groups are amines.
o The amino group acts as a base because it can pick up a hydrogen ion (H+) from the solution.
o Amino acids, the building blocks of proteins, have amino and carboxyl groups.
A sulfhydryl group (—SH) consists of a sulfur atom bonded to a hydrogen atom and to the
backbone.
o This group resembles a hydroxyl group in shape.
o Organic molecules with sulfhydryl groups are thiols.
o Two sulfhydryl groups can interact to help stabilize the structure of proteins.
A phosphate group (—OPO32−) consists of a phosphorus atom bound to four oxygen atoms (three
with single bonds and one with a double bond).
o A phosphate group connects to the carbon backbone via one of its oxygen atoms.
o Phosphate groups are anions with two negative charges because 2 protons dissociate from the
oxygen atoms.
o One function of phosphate groups is to transfer energy between organic molecules.
7
ATP is an important source of energy for cellular processes.
Adenosine triphosphate, or ATP, is the primary energy transfer molecule in living cells.
ATP consists of an organic molecule called adenosine attached to a string of three phosphate groups.
When one inorganic phosphate ion is split off as a result of a reaction with water, ATP becomes
adenosine diphosphate, or ADP.
In a sense, ATP ―stores‖ the potential to react with water, releasing energy that can be used by the
cell.
8
Chapter 5: The Structure and Function of Large Biological Molecules
Overview: The Molecules of Life
9
The covalent bonds that connect monomers in a polymer are disassembled by hydrolysis, a reaction
that is effectively the reverse of dehydration.
○ In hydrolysis, bonds are broken by the addition of water molecules. A hydrogen atom attaches to
one monomer, and a hydroxyl group attaches to the adjacent monomer.
○ The process of digestion is an example of hydrolysis within the human body.
○ The cells of our body then use dehydration reactions to assemble the monomers into new and
different polymers that carry out functions specific to the particular cell type.
10
Structure and classification of some monosaccharides
Ribose-component of RNA
Although glucose is often drawn with a linear carbon skeleton, most sugars (including glucose) form
rings in aqueous solution.
Monosaccharides, particularly glucose, are major nutrients for cellular work.
○ Cells extract energy from glucose molecules in the process of cellular respiration.
Simple sugars also function as the raw material for the synthesis of other monomers, such as amino
acids and fatty acids.
Linear & ring forms of glucose
11
Two monosaccharides can join with a glycosidic linkage to form a disaccharide via dehydration.
○ Maltose, malt sugar, is formed by joining two glucose molecules.
○ Sucrose, table sugar, is formed by joining glucose and fructose. Sucrose is the major transport
form of sugars in plants.
○ Lactose, milk sugar, is formed by joining glucose and galactose.
Disaccharide synthesis
12
Structures of polysaccharides Starch and cellulose structures
Like starch, cellulose is a polymer of glucose. However, the glycosidic linkages in these two
polymers differ.
○ The linkages are different because glucose has two slightly different ring structures.
○ These two ring forms differ in whether the hydroxyl group attached to the number 1 carbon is
fixed above ( glucose) or below ( glucose) the plane of the ring.
Starch is a polysaccharide of alpha () glucose monomers.
Cellulose is a polysaccharide of beta () glucose monomers, making every other glucose monomer
upside down with respect to its neighbors.
The differing glycosidic linkages in starch and cellulose give the two molecules distinct three-
dimensional shapes.
Enzymes that digest starch by hydrolyzing its linkages cannot hydrolyze the linkages in
cellulose.
○ Cellulose in human food passes through the digestive tract and is eliminated in feces as
―insoluble fiber.‖
Some microbes can digest cellulose to its glucose monomers through the use of cellulase enzymes.
Many eukaryotic herbivores, from cows to termites, have symbiotic relationships with cellulose-
digesting prokaryotes and protists, providing the microbes and the host animal access to a rich source
of energy.
Another important structural polysaccharide is chitin, found in the exoskeletons of arthropods
(including insects, spiders, and crustaceans).
○ Chitin is similar to cellulose, except that it has a nitrogen-containing appendage on each glucose
monomer.
○ Chitin also provides structural support for the cell walls of many fungi.
13
5.3 Lipids are a diverse group of hydrophobic molecules
Unlike other macromolecules, lipids do not form polymers.
The unifying feature of lipids is that they have little or no affinity for water because they consist of
mostly hydrocarbons, which form nonpolar covalent bonds.
Fatty acids vary in length (number of carbons) and in the number and locations of double bonds.
○ If the fatty acid has no carbon-carbon double bonds, then the molecule is a saturated fatty acid,
saturated with hydrogens at every possible position.
○ If the fatty acid has one or more carbon-carbon double bonds formed by the removal of hydrogen
atoms from the carbon skeleton, then the molecule is an unsaturated fatty acid.
A saturated fatty acid is a straight chain, but an unsaturated fatty acid has a kink wherever there is a
cis double bond.
○ The kinks caused by the cis double bonds prevent the molecules from packing tightly enough to
solidify at room temperature.
Fats made from saturated fatty acids are saturated fats. Fats made from unsaturated fatty acids are
unsaturated fats.
○ Most animal fats are saturated and are solid at room temperature.
○ Plant and fish fats are liquid at room temperature and are known as oils.
14
Saturated triglyceride Monounsaturated triglyceride
The phrase ―hydrogenated vegetable oils‖ on food labels means that unsaturated fats have been
synthetically converted to saturated fats by the addition of hydrogen.
○ Peanut butter and margarine are hydrogenated to prevent lipids from separating out as oil.
A diet rich in saturated fats may contribute to cardiovascular disease (atherosclerosis) through plaque
deposits.
Some unsaturated fatty acids cannot be synthesized by humans and must be supplied by diet.
○ Omega-3 fatty acids are essential fatty acids.
The major function of fats is energy storage.
○ A gram of fat stores more than twice as much energy as a gram of a polysaccharide such as
starch.
○ Because plants are immobile, they can function with bulky energy storage in the form of starch.
Plants use oils when dispersal and compact storage are important, as in seeds.
○ Animals must carry their energy stores with them, so they benefit from having a more compact
fuel reservoir of fat.
Humans and other mammals store fats as long-term energy reserves in adipose cells that swell and
shrink as fat is deposited and withdrawn from storage.
A layer of fat can function as insulation.
15
Structural formula of a phospholipid Phospholipid bilayer
Phospholipid symbol
Cholesterol is the precursor from which all other steroids are synthesized.
○ Many of these other steroids are hormones, including the vertebrate sex hormones.
Although cholesterol is an essential molecule in animals, high levels of cholesterol in the blood may
contribute to cardiovascular disease.
16
○ Each type of protein has a complex three-dimensional shape.
All proteins are unbranched polymers constructed from the same 20 amino acid monomers.
Polymers of amino acids are called polypeptides.
A protein is a biologically functional molecule that consists of one or more polypeptides folded and
coiled into a specific conformation.
Overview of protein functions
Amino acids are the monomers from which proteins are constructed.
Amino acids are organic molecules with both carboxyl and amino groups.
At the center of an amino acid is an asymmetric carbon atom called the alpha () carbon.
17
Amino acid monomer
Four components are attached to the α carbon: a hydrogen atom, a carboxyl group, an amino group,
and a variable R group (or side chain).
○ Different R groups characterize the 20 different amino acids.
○ An R group may be as simple as a hydrogen atom (as in the amino acid glycine), or it may be a
carbon skeleton with various functional groups attached (as in glutamine).
The physical and chemical properties of the R group determine the unique characteristics of a
particular amino acid.
○ One group of amino acids has nonpolar R groups, which are hydrophobic.
○ Another group of amino acids has polar R groups, which are hydrophilic.
○ A third group of amino acids has functional groups that are charged (ionized) at cellular pH.
o Some acidic R groups have negative charge due to the presence of a carboxyl group.
o Basic R groups have amino groups with positive charge.
o All amino acids have carboxyl and amino groups. The terms acidic and basic in this context refer
only to these groups in the R groups.
Examples of amino acid types
Nonpolar; hydrophobic Polar; hydrophilic Acidic (negative charge) Basic (positive charge)
Amino acids are joined together when a dehydration reaction removes a hydroxyl group from the
carboxyl end of one amino acid and a hydrogen atom from the amino group of another.
○ The resulting covalent bond is called a peptide bond.
Repeating the process over and over creates a polypeptide chain.
○ At one end is an amino acid with a free amino group (the N-terminus), and at the other end is an
amino acid with a free carboxyl group (the C-terminus).
Polypeptides range in size from a few monomers to thousands.
Each polypeptide has a unique linear sequence of amino acids.
18
Making a polypeptide chain
19
○ The weakly positive hydrogen atom attached to the nitrogen atom has an affinity for the oxygen
atom of a nearby peptide bond.
○ Each hydrogen bond is weak, but the sum of many hydrogen bonds stabilizes the structure of
part of the protein.
One secondary structure is the helix, a delicate coil held together by hydrogen bonding between
every fourth amino acid
○ Some fibrous proteins, such as -keratin, the structural protein of hair, have the helix
formation over most of their length.
The other main type of secondary structure is the pleated sheet.
○ In this structure, two or more regions of the polypeptide chain lying side by side are connected
by hydrogen bonds between parts of the two parallel polypeptide backbones.
○ Pleated sheets are found in many globular proteins, such the silk protein of a spider’s web.
○ The presence of so many hydrogen bonds makes each silk fiber stronger than a steel strand of the
same weight.
Primary structure – linear chain of amino Secondary structure- stabilized by hydrogen bonds
acids between atoms of the polypeptide backbone
20
Tertiary Structure- three dimensional shape Interactions that shape a tertiary structure
stabilized by interactions between side chains
Quaternary structure results from the aggregation of two or more polypeptide subunits.
○ For example, globular transthyretin protein is made up of four polypeptides.
○ Collagen is a fibrous protein made up of three polypeptides that are supercoiled into a larger
triple helix.
○ Hemoglobin is a globular protein with quaternary structure.
Hemoglobin consists of four polypeptide subunits: two and two chains.
Both types of subunits consist of primarily -helical secondary structure.
Each subunit has a nonpeptide heme component with an iron atom that binds oxygen.
A polypeptide chain with a given amino acid sequence can spontaneously arrange itself into a three-
dimensional shape determined and maintained by the interactions responsible for secondary and
tertiary structure.
○ The folding occurs as the protein is synthesized within the cell.
Protein structure also depends on the physical and chemical conditions of the protein’s environment.
○ Alterations in pH, salt concentration, temperature, or other factors can unravel or denature a
protein.
21
○ These forces disrupt the weak chemical bonds and interactions within a protein that maintain its
shape.
○ Because it is misshapen, a denatured protein is biologically inactive.
Most proteins become denatured if they are transferred from an aqueous environment to a nonpolar
solvent.
○ The polypeptide chain refolds so that its hydrophobic regions face outward, toward the solvent.
Other denaturation agents include chemicals that disrupt the hydrogen bonds, ionic bonds, and
disulfide bridges that maintain a protein’s shape.
Denaturation can also be caused by heat, which disrupts the weak interactions that stabilize
conformation.
○ This explains why extremely high fevers can be fatal. Proteins in the blood become denatured by
the high body temperatures.
Some, but not all, proteins can return to their functional shape after denaturation.
○ This suggests that the information for building a specific shape is intrinsic to the protein’s
primary structure.
Most proteins appear to undergo several intermediate stages before reaching their ―mature‖ structure.
Even a slight change in the primary structure can affect a protein’s conformation and ability to
function.
○ The substitution of one amino acid (valine) for the normal one (glutamic acid) at a particular
position in the primary structure of hemoglobin, the protein that carries oxygen in red blood
cells, can cause sickle-cell disease, an inherited blood disorder.
22
The folding of many proteins is assisted by chaperonins, or chaperone proteins.
○ Chaperonins do not specify the final structure of a polypeptide but rather work to segregate and
protect the polypeptide while it folds spontaneously.
Chaperonins
o Molecular systems in the cell interact with chaperonins, marking incorrectly folded proteins for
refolding or for destruction.
Accumulation of incorrectly folded polypeptides is associated with many diseases, including
Alzeimer’s, Parkinson’s, and mad cow disease.
In 2006, Roger Kornberg received the Nobel Prize in Chemistry for elucidating the structure of RNA
polymerase, which plays a crucial role in the expression of genes.
○ Kornberg and his colleagues used X-ray crystallography to determine the three-dimensional
structure of this protein.
○ Nuclear magnetic resonance (NMR) spectroscopy, which does not require protein crystallization,
can also be used to determine protein structure.
Bioinformatics uses computer programs to predict the three-dimensional structures of polypeptides
from their amino acid sequences.
X-ray crystallography, NMR spectroscopy, and bioinformatics are complementary approaches,
contributing a great deal to our understanding of protein structure and function.
5.5 Nucleic acids store, transmit, and help express hereditary information
The amino acid sequence of a polypeptide is programmed by a discrete unit of inheritance known as
a gene.
o A gene consists of DNA, a polymer known as a nucleic acid.
o Nucleic acids are made of monomers called nucleotides.
23
Although DNA encodes the information that programs all the cell’s activities, it is not directly
involved in the day-to-day operations of the cell.
Each gene along a DNA molecule directs the synthesis of a specific type of RNA called messenger
RNA (mRNA).
○ The mRNA molecule interacts with the cell’s protein-synthesizing machinery to direct the
ordering of amino acids in a polypeptide.
The flow of genetic information is DNA mRNA protein.
24
Polynucleotides are synthesized when adjacent nucleotides are joined by covalent bonds called
phosphodiester linkages that form between the —OH group on the 3 of one nucleotide and the
phosphate on the 5 carbon of the next.
○ This process creates a repeating backbone of sugar-phosphate units, with appendages consisting
of the nitrogenous bases.
The two free ends of the polymer are distinct.
○ One end has a phosphate attached to a 5 carbon; this is the 5 end.
○ The other end has a hydroxyl group on a 3 carbon; this is the 3 end
DNA
The sequence of bases along a DNA or mRNA polymer is unique for each gene.
○ Because genes are normally hundreds to thousands of nucleotides long, the number of possible
base combinations is virtually limitless.
The linear order of bases in a gene specifies the order of amino acids—the primary structure—of a
protein, which in turn determines three-dimensional structure and function.
Messenger RNA
25
Components of nucleic acids
Complementary base pairing can also occur between parts of two RNA molecules or even between
two stretches of nucleotides in the same RNA molecule.
○ For example, transfer RNA or tRNA brings amino acids to the ribosome during polypeptide
synthesis.
○ The functional shape of tRNA results from base pairing between nucleotides where
complementary stretches of the molecule run antiparallel to each other.
In RNA, adenine pairs with uracil; thymine is not present in RNA.
Another difference between RNA and DNA is that DNA almost always exists as a double helix,
whereas RNA molecules are more variable in shape.
5.6 Genomics and proteomics have transformed biological inquiry and applications
The structure of the DNA molecule was described in 1952, and the linear sequence of nucleotide
bases was understood to specific the amino acid sequence of proteins.
The first chemical techniques for DNA sequencing were developed in the 1970s.
Between 1990 and the early 2000s, the entire sequence of the full complement of the human genome
was sequenced, the human genome project.
Rapid development of faster and less expense sequencing methods have led to the sequencing of
numerous genomes, other than humans.
o A new disciple, bioinformatics, using computer software and computational tools, was formed to
handle and analyze the large reams of data generated from these endeavors.
o Genomics is an approach of addressing problems by analyzing large sets of genes or comparing
whole genomes of different species.
o Similar to genomics, proteomic is the approach that analyzes large sets of protein sequences.
27
DNA and proteins are used as a tape measures of evolution.
Genes (DNA) and their products (proteins) document the hereditary background of an organism.
Because DNA molecules are passed from parents to offspring, siblings have greater similarity in
their DNA and protein than do unrelated individuals of the same species.
This argument can be extended to develop a ―molecular genealogy‖ to relationships between species.
Two species that appear to be closely related based on fossil and molecular evidence should also be
more similar in DNA and protein sequences than are more distantly related species.
○ Scientists can compare the sequence of 146 amino acids in the polypeptide chain of human
hemoglobin to the sequences in five other vertebrates.
○ Humans and gorillas differ in just 1 amino acid, while humans and frogs differ in 67 amino
acids.
○ Despite these differences, all the species have functional hemoglobin.
28
Chapter 8: An Introduction to Metabolism
Overview:
Concept 8.1 An organism’s metabolism transforms matter and energy, subject to the laws of
thermodynamics.
The sum total of an organism’s chemical reactions is called metabolism.
Metabolism is an emergent property of life that arises from interactions between molecules within
the orderly environment of the cell.
Catabolic pathways release energy by breaking down complex molecules to simpler compounds.
A major pathway of catabolism is cellular respiration, in which the sugar glucose is broken down
in the presence of oxygen to carbon dioxide and water.
The energy released by catabolic pathways becomes available to do the work of the cell, such as
ciliary beating or membrane transport.
Anabolic pathways, also called biosynthetic pathways, consume energy to build complicated
molecules from simpler compounds.
The synthesis of amino acids from simpler molecules and the synthesis of a protein from amino
acids are both examples of anabolism.
Energy released from the ―downhill‖ reactions of catabolic pathways can be stored and then used to
drive the ―uphill‖ reactions of anabolic pathways.
Energy is fundamental to all metabolic processes, and therefore an understanding of energy is key to
understanding how the living cell works.
Bioenergetics is the study of how energy flows through living organisms.
Organisms transform energy.
Energy is the capacity to cause change.
29
In everyday life, some forms of energy can be used to do work—that is, to move matter against
opposing forces, such as gravity and friction.
Energy exists in various forms, and cells transform energy from one type to another.
Kinetic energy is the energy associated with the relative motion of objects.
Objects in motion can perform work by imparting motion to other matter.
Thermal energy is kinetic energy associated with the random movement of atoms or molecules.
Heat is the transfer of thermal energy from one body of matter to another.
The energy of light can be harnessed to power photosynthesis in green plants.
Potential energy is the energy that matter possesses because of its location or structure.
Water behind a dam possesses energy because of its altitude above sea level.
Molecules possess energy because of the arrangement of electrons in the bonds between their
atoms.
Chemical energy is a term used by biologists to refer to the potential energy available for release
in a chemical reaction.
During a catabolic reaction, some bonds are broken and others are formed, releasing energy and
producing lower-energy breakdown products.
Energy can be converted from one form to another.
30
Entropy is a measure of disorder or randomness: The more random a collection of matter, the
greater its entropy.
The second law of thermodynamics states: Every energy transfer or transformation increases the
entropy of the universe.
Although order can increase locally, there is an unstoppable trend toward randomization of the
universe.
Much of the increased entropy of the universe takes the form of increasing heat, which is the energy
of random molecular motion.
In most energy transformations, ordered forms of energy are converted at least partly to heat.
Automobiles convert only 25% of the energy in gasoline to motion; the rest is lost as heat.
Living cells unavoidably convert organized forms of energy to heat.
For a process to occur on its own, without outside help in the form of energy input, it must
increase the entropy of the universe.
Spontaneous processes can occur without an input of energy, although they need not occur quickly.
Some spontaneous processes, such as an explosion, are instantaneous. Some, such as the rusting
of an old car, are very slow.
A spontaneous process is one that is energetically favorable. A process that cannot occur on its own
is said to be nonspontaneous: it will happen only if energy is added to the system.
Water flows downhill spontaneously but moves uphill only with an input of energy, such as
when a machine pumps the water against gravity.
Here is another way to state the second law of thermodynamics: For a process to occur
spontaneously, it must increase the entropy of the universe.
Living systems increase the entropy of their surroundings, even though they create ordered structures
from less ordered starting materials.
For example, amino acids are ordered into polypeptide chains.
The structure of a multicellular body is organized and complex.
However, an organism also takes in organized forms of matter and energy from its surroundings and
replaces them with less ordered forms.
For example, an animal consumes organic molecules as food and catabolizes them to low-energy
carbon dioxide and water.
8.2 The free-energy change of a reaction tells us whether or not the reaction occurs
spontaneously.
How can we determine which reactions occur spontaneously and which ones require an input of
energy?
The concept of free energy (symbolized by the letter G) is useful for measuring the spontaneity of a
system.
Free energy is the portion of a system’s energy that can perform work when temperature and
pressure are uniform throughout the system, as in a living cell.
The change in free energy, ∆G, can be calculated for any specific chemical reaction by applying the
following equation:
∆G = ∆H – T∆S
In this equation, ∆H symbolizes the change in the system’s enthalpy (in biological systems,
equivalent to total energy); ∆S is the change in the system’s entropy; and T is the absolute
temperature in Kelvin (K) units (K = °C + 273).
For a process to occur spontaneously, the system must give up enthalpy (H must decrease), give up
order (T∆S must increase), or both.
∆G must have a negative value (∆G < 0) in order for a process to be spontaneous.
In other words, every spontaneous process decreases the system’s free energy, and processes that
have positive or zero ∆G are never spontaneous.
31
Knowing the value of G gives biologists the power to predict which kinds of change can happen
without help.
Such spontaneous changes can be harnessed to perform work.
This information is important in the study of metabolism, where a major goal is to determine
which reactions can supply energy to do work in the living cell.
In any spontaneous process, the free energy of a system decreases (∆G is negative).
We can represent the change in free energy from the start to the finish of a process by
G = Gfinal state − Gstarting state
∆G can be negative only when the process involves a loss of free energy during the change from
initial state to final state.
Because it has less free energy, the system in its final state is less likely to change and is therefore
more stable than it was previously.
A system at equilibrium is at maximum stability.
Unstable systems (higher G) tend to change in such a way that they become more stable (lower
G).
Another term for a state of maximum stability is equilibrium.
In a chemical reaction at equilibrium, the rates of forward and backward reactions are equal, and
there is no change in the relative concentrations of products or reactants.
At equilibrium, G = 0, and the system can do no work.
A process is spontaneous and can perform work only when it is moving toward equilibrium.
Movements away from equilibrium are nonspontaneous and will have a positive G.
The relationship of free energy (G) to stability, work capacity, and spontaneous change
32
For the overall reaction of cellular respiration, C6H12O6 + 6O2 6CO2 + 6H2O, G = 686
kcal/mol.
For each mole (180 g) of glucose broken down by respiration under standard conditions (1 M of
each reactant and product, 25°C, pH 7), 686 kcal of energy are made available to do work in the
cell.
The products have 686 kcal less free energy per mole than the reactants.
An endergonic reaction is one that absorbs free energy from its surroundings.
Endergonic reactions store energy in molecules; G is positive.
Endergonic reactions are nonspontaneous, and the magnitude of G is the quantity of energy
required to drive the reaction.
If cellular respiration releases 686 kcal/mol, then photosynthesis, the reverse reaction, must require
an equivalent investment of energy.
For the conversion of carbon dioxide and water to sugar, G = +686 kcal/mol.
Photosynthesis is strongly endergonic, powered by the absorption of light energy.
Reactions in an isolated system eventually reach equilibrium and can do no work.
A cell that has reached metabolic equilibrium has a G = 0 and is dead!
Metabolic disequilibrium is one of the defining features of life.
Cells maintain disequilibrium because they are open systems. The constant flow of materials into and
out of the cell keeps metabolic pathways from ever reaching equilibrium.
A cell continues to do work throughout its life.
A catabolic process in a cell releases free energy in a series of reactions, not in a single step.
Work in an open system
33
Some reversible reactions of respiration are constantly ―pulled‖ in one direction, as the product of
one reaction does not accumulate but becomes the reactant in the next step.
The overall sequence of reactions is kept going by the huge free-energy difference between glucose
and oxygen at the top of the energy ―hill‖ and carbon dioxide and water at the ―downhill‖ end.
As long as cells have a steady supply of glucose or other fuels and oxygen and can expel waste
products to the surroundings, their metabolic pathways never reach equilibrium and can continue to
do the work of life.
Sunlight provides a daily source of free energy for photosynthetic organisms.
Nonphotosynthetic organisms depend on a transfer of free energy from photosynthetic organisms in
the form of organic molecules.
8.3 ATP powers cellular work by coupling exergonic reactions to endergonic reactions.
A cell does three main kinds of work:
1. Chemical work, pushing endergonic reactions such as the synthesis of polymers from monomers;
2. Transport work, pumping substances across membranes against the direction of spontaneous
movement;
3. Mechanical work, such as the beating of cilia, contraction of muscle cells, and movement of
chromosomes during cellular reproduction;
Cells manage their energy resources to do this work by energy coupling, using an exergonic process
to drive an endergonic one.
ATP is responsible for mediating most energy coupling in cells
In most cases, ATP acts as the immediate source of energy that powers cellular work.
The bonds between the phosphate groups on ATP can be broken by hydrolysis.
When the terminal phosphate bond is broken, a molecule of inorganic phosphate (HOPO32-,
abbreviated Pi here) leaves ATP, which then becomes adenosine diphosphate, or ADP:
ATP + H2O ADP + Pi
G = 7.3 kcal/mol (30.5 kJ/mol).
In the cell, G for the hydrolysis of ATP is about −13 kcal/mol because reactant and product
concentrations differ from 1 M.
Although the phosphate bonds of ATP are sometimes referred to as high-energy phosphate bonds,
these are actually fairly weak covalent bonds.
34
The reactants (ATP and water) themselves have high energy relative to the energy of the
products (ADP and Pi).
The release of energy during the hydrolysis of ATP comes from the chemical change to a state of
lower free energy, not from the phosphate bonds themselves.
Why does the hydrolysis of ATP yield so much energy?
o Each of the three phosphate groups has a negative charge.
o These three like charges are crowded together, and their mutual repulsion contributes to the
instability of this region of the ATP molecule.
o The triphosphate tail of ATP is the chemical equivalent of a compressed spring.
In the cell, the energy from the hydrolysis of ATP is directly coupled to endergonic processes by the
transfer of the phosphate group to another molecule.
This recipient molecule with a phosphate group covalently bonded to it is called a phosphorylated
intermediate. It is more reactive (less stable) than the original unphosphorylated molecule.
Mechanical, transport, and chemical work in the cell are nearly always powered by the hydrolysis of
ATP.
In each case, ATP hydrolysis leads to a change in a protein’s shape and often its ability to bind
another molecule.
This change may occur via a phosphorylated intermediate.
ATP drives chemical work – energy coupling and ATP hydrolysis
In most examples of mechanical work involving motor proteins ―walking‖ on cytoskeletal elements,
a cycle occurs in which ATP is bound noncovalently to the motor protein and hydrolyzed, then ADP
and Pi are released, followed by binding of another ATP molecule.
In each state, the motor protein exhibits a different shape and ability to bind the cytoskeleton,
resulting in movement of the protein along the cytoskeletal track.
35
How ATP drives transport and mechanical work
A working muscle cell recycles its entire pool of ATP once each minute.
More than 10 million ATP molecules are consumed and regenerated per second per cell.
Regeneration of ATP is an endergonic process, requiring an investment of energy:
ADP + Pi ATP + H2O
G = +7.3 kcal/mol
Catabolic (exergonic) pathways, especially cellular respiration, provide the energy for the endergonic
regeneration of ATP.
Plants also use light energy to produce ATP.
The chemical potential energy temporarily stored in ATP drives most cellular work.
36
To hydrolyze sucrose, the bond between glucose and fructose must be broken and new bonds
must form with hydrogen and hydroxyl ions from water.
To reach a state at which bonds can break and reform, reactant molecules must absorb energy from
their surroundings. When the new bonds of the product molecules form, energy is released as heat as
the molecules assume stable shapes with lower energy.
The initial investment of energy for starting a reaction is the free energy of activation, or activation
energy (EA).
Activation energy is the amount of energy necessary to push the reactants over an energy barrier so
that the ―downhill‖ part of the reaction can begin.
Activation energy is often supplied in the form of thermal energy that the reactant molecules absorb
from the surroundings.
The absorption of thermal energy accelerates the reactant molecules, which then collide more
often with more force.
It also agitates the atoms within the molecules, making the breakage of bonds more likely.
When the molecules have absorbed enough energy for the bonds to break, the reactants are in an
unstable condition called the transition state.
Consider a hypothetical exergonic reaction that swaps portions of two reactant molecules:
AB + CD AC + BD
Energy profile of an exergonic reaction
The energizing, or activation, of the reactants is represented by the uphill portion of the graph, with
the free-energy content of the reactant molecules increasing.
At the summit, when the energy equivalent to EA has been absorbed, the reactants are in the
transition state. They are activated and their bonds can be broken.
The bond-forming phase of the reaction corresponds to the downhill part of the curve, which shows
the loss of free energy by the molecules.
As the molecules settle into new, stable bonding arrangements, energy is released to the
surroundings.
The overall decrease in free energy means that EA is repaid with interest.
For some processes, EA is not high, and the thermal energy provided by room temperature is
sufficient for many reactants to reach the transition state.
37
In most cases, EA is high enough that the transition state is rarely reached and the reaction hardly
proceeds at all. In these cases, the reaction will occur at a noticeable rate only if the reactants are
heated.
A spark plug provides the activation energy to energize a gasoline-oxygen mixture and cause
combustion.
Without a spark, the hydrocarbons of gasoline are too stable to react with oxygen.
Proteins, DNA, and other complex organic molecules are rich in free energy. Their hydrolysis is
spontaneous, with the release of large amounts of energy.
However, there is not enough energy at the temperatures typical of the cell for the vast majority of
organic molecules to make it over the hump of activation energy.
How are the barriers for selected reactions surmounted to allow cells to carry out the processes of
life?
Heat would speed up all reactions, not just those that are needed.
Heat also denatures proteins and kills cells.
Enzymes speed reactions by lowering EA. The transition state can then be reached even at moderate
temperatures.
Enzymes do not change G; they hasten reactions that would occur eventually.
Because enzymes are so selective, they determine which chemical processes will occur at any time.
The effect of an enzyme on activation energy
Exergonic
Endergonic
38
Enzymes are substrate specific.
The reactant that an enzyme acts on is the substrate.
The enzyme binds to a substrate, or substrates, forming an enzyme-substrate complex.
While the enzyme and substrate are bound, the catalytic action of the enzyme converts the substrate
to the product or products.
39
The active site and catalytic cycle of an enzyme
The rate at which a specific number of enzymes convert substrates to products depends in part on
substrate concentrations.
At low substrate concentrations, an increase in substrate concentration speeds binding to available
active sites.
There is a limit to how fast a reaction can occur, however.
At high substrate concentrations, the active sites on all enzymes are engaged.
The enzyme is saturated, and the rate of the reaction is determined by the speed at which the
active site can convert substrate to product.
○ The only way to increase productivity at this point is to add more enzyme molecules.
Many enzymes require nonprotein helpers, called cofactors, for catalytic activity.
Cofactors bind permanently or reversibly to the enzyme.
Some inorganic cofactors are zinc, iron, and copper in ionic form.
Organic cofactors are called coenzymes.
Most vitamins are coenzymes or the raw materials from which coenzymes are made.
Some reversible inhibitors resemble the substrate and compete for binding to the active site. These
molecules are called competitive inhibitors.
Competitive inhibition can be overcome by increasing the concentration of the substrate.
Noncompetitive inhibitors impede enzymatic reactions by binding to another part of the molecule.
Binding by the inhibitor causes the enzyme to change shape, rendering the active site less
effective at catalyzing the reaction.
Toxins and poisons are often irreversible enzyme inhibitors.
o DDT acts as a pesticide by inhibiting key enzymes in the nervous system of insects.
Many antibiotics are inhibitors of specific enzymes in bacteria.
Penicillin blocks the active site of an enzyme that many bacteria use to make their cell walls.
Not all enzyme inhibitors are metabolic poisons.
Molecules naturally present in the cell often regulate enzyme activity by acting as inhibitors.
Such regulation—selective inhibition—is essential to the control of cellular metabolism.
41
A permanent change in a gene, known as a mutation, can result in a protein with one or more
changed amino acids.
In an enzyme, if the changed amino acids are in the active site or some other crucial region, the
altered enzyme might have a novel activity or it might bind to a different substrate.
Under environmental conditions where the new function benefits the organism, natural selection
would tend to favor the mutated form of the gene, causing it to persist in the population.
Researchers have used a lab procedure that mimics evolution in natural populations.
Using molecular techniques, the researchers introduced random mutations into E. coli genes and then
tested the bacteria for their ability to break down a slightly different disaccharide.
The researchers found that six amino acids had changed in the enzyme altered in this experiment.
Two of these changed amino acids were in the active site, two were nearby, and two were on the
surface of the protein.
As the chemical conditions in the cell shift, the pattern of allosteric regulation may shift as well.
By binding to key enzymes, the reactants and products of ATP hydrolysis may play a major role in
balancing the flow of traffic between anabolic and catabolic pathways.
42
For example, ATP binds to several catabolic enzymes allosterically, inhibiting their activity by
lowering their affinity for substrate.
ADP functions as an activator of the same enzymes.
ATP and ADP also affect key enzymes in anabolic pathways.
In this way, allosteric enzymes control the rates of key reactions in metabolic pathways.
In enzymes with multiple catalytic subunits, binding by a substrate molecule to one active site in a
multisubunit enzyme triggers a shape change in all the subunits.
This mechanism, called cooperativity, amplifies the response of enzymes to substrates, priming
the enzyme to accept additional substrates.
Cooperativity is considered to be ―allosteric‖ regulation because binding of the substrate to one
active site affects catalysis in a different active site.
Cooperativity – another type of allosteric activation
43
Feedback inhibition in isoleucine synthesis
44