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CHEMISTRY OF LIFE
CHM 1313
Centre of Pre-U Studies
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Content
Protein chemistry
Genetic information
Energy Metals in biological systems
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11.1 The Chemistry of life
At the end of this course candidates
should be aware of the diverse variety of
roles played by proteins. These will beillustrated by examples in this section and
in sections 11.2 and 11.3. The recall of
specific examples will not be tested but
candidates will be expected to discuss thechemistry of given examples.
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Learning Outcomes
Recall that proteins are condensation
polymers formed from amino-acid
monomers and recognise and describe thegeneralised structure of amino acids
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ProteinsA protein chain will have somewhere in the range of50 to20002-amino acid residues.
Every protein has a similar backbone of carbon and nitrogenatoms held together by peptide bonds:
protein backbone (in box)
The proteins are difference in the length of the backboneand the sequence of the side chains (R groups) that areattached to the backbone.
-CCNCCNCCNCCNCC-
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Learning Outcome
Explain the importance of amino acid
sequence (primary structure) in
determining the properties of proteins
Distinguish between the primary,
secondary and tertiary structure of
proteins and explain the stabilisation of
secondary and tertiary structure using thechemistry learnt in the core syllabus.
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Primary Protein
refer to the linear sequence of amino acidand as such has an amino terminal end anda carboxy terminal end.
Each different protein in a biologicalorganism has a unique sequence of aminoacid residues.
The sequence that causes a protein chainto fold and curl into the distinctive shape and
enables the protein to function properly.
Only covalent bonds exist.7
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Primary structure of the enzyme lysozyme found in hen egg white
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1.Secondary protein structure is refer when the chain can berotated about carbon-to-carbon bonds to make it twist or fold.
2.The common secondary structures are the -helix (alpha helix)and the F-pleated (beta pleated) sheet.
a) -helix
The helical structure in proteins is coiled like a loosely-coiledspring that is stabilised by hydrogen bonds between carbonyloxygen and amide hydrogen.
The carbonyl group of each amino acid is hydrogen-bonded tothe amide hydrogen of the four amino acid in the chain.
The sequence of amino acids is important because the groupsthat form side-chains in a protein can interact with other side
chains further along the chains as it bends.(see tertiarystructure)
In the proteins -keratin (found in hair), myosin
(found in muscle), epidermin (found in skin), and
fibrin (found in blood clots), two or more helices
interact (supracoiling) to form a cable.
Secondary Protein
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The - helix - a deeper look
- Right-hand screw
- The R groups stick
out from the spiral.
-Each peptide group is
involved in two
hydrogen bonds. All
the N-H groups arepointing upwards, and
all the C=O groups
pointing downwards.
Each of them is
involved in a hydrogen
bond.
Each complete turn of the spiral has 3.6 (approximately) amino acid residues
in it.
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Proline is an amino acid that does not form an
alpha helix because of its cyclic structure, the
structure becomes destabilised.
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b) F-pIeated sheetIn a beta-pleated sheet,.
A secondary protein structure in which the chains are folded
so that they lie alongside each other held together by hydrogenbonds.
F-pleated sheet is found extensively only in the protein of silk.
The repeating secondary structure with its multitude of
hydrogen bonds provides the protein with strength and rigid.
F -pleated sheet
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The folded chains are again held together
by hydrogen bonds involving exactly the
same groups as in the alpha-helix.
The R groups point above and below the sheet.
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Tertiary protein structure
A specific three-dimensional shape of a protein resulting
from interactions between R groups/ side chains of the2-amino acid residues in the protein.
The tertiary structure results from interactions between theR side chains of the amino acid residues. These R-groupinteractions are of four types:
1. Disulfide bridges: As in the structure of insulin, a disulfidelinkage can form between two cysteine residues that areclose to each other in the same chain or between cysteineresidues in different chains.
2. Salt bridges: These interactions are a result of ionic bondsthat form between the ionized side chain of an acidic amino
acid (-COO-) and the side chain of a basic amino acid (-NH3
+).
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3. Hydrogen bonds: Hydrogen bonds can form between a
variety of side chains, e.g. between the OH group or
between backbone C=O and NH group.
4. Hydrophobic interactions: These result when non-polar
groups are either attracted to each other or forced together
by their mutual repulsion of aqueous solvent. Interactions of
this type are common between R groups such as the non-
polar phenyl rings.
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June 2008
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1) Ionic bonds between charged R
groupsBetween two oppositively charged side
chains(e.g Aspartic acid and Lysine)
usually groups that ionise in water
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2) Hydrogen bonds between polar
R groups
Between polar side chains(-OH, -NH,=O, =NRgroups)
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Several amino acids have quite large hydrocarbon groups in their side chains. A few
examples are shown below. Temporary fluctuating dipoles in one of these groups
could induce opposite dipoles in another group on a nearby folded chain.
The forces set up would be enough to hold the folded structure together.
3. Van der Waals forces between
non-polar molecules
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4) Sulphur bridgesIt involves the amino acid cysteine.
If two cysteine side chains end up next to
each other because of folding in the
peptide chain, they can react to form a
sulphur bridge.
R-SH + HS-R +[O] R-S-S-R + H2O
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The alpha helix are shown
The beta pleatedsheets are shown
The disulphide
bridges are shown by
purple atoms bondedtogether.
The bits of the protein chain
which are just random coils
and loops are shown as bits
of "string".
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Quaternary Structure of Proteins
A protein which contains two polypeptides
chains that combine. The example shown
is haemoglobin
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The structure of haemoglobin contains four polypeptide chains.
Two chains are called
chains and the other two arecalled chains. (Not related
to helix and pleated
sheets).
Haemoglobin contains
such a group known as
haem, which is a large,iron-containing molecule
which gives haemoglobin
its red colour and is
responsible for binding
the oxygen that
haemoglobin transportsround the blood stream.
Each protein chain is
bonded to one haem
group.
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The functional part of this
is an iron(II) ion
surrounded by a
complicated molecule
called haem. This is a sort
of hollow ring of carbonand hydrogen atoms, at
the centre of which are 4
nitrogen atoms with lone
pairs on them.
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Overall, the complex ion has a co-ordination number of6
because the central metal ion is forming 6 co-ordinatebonds.
The water molecule which is bonded to the bottom position
in the diagram is easily replaced by an oxygen molecule
(again via a lone pair on one of the oxygens in O2) - and
this is how oxygen gets carried around the blood by thehaemoglobin.
When the oxygen gets to where it is needed, it breaks
away from the haemoglobin which returns to the lungs to
get some more.
Hb + 4O2 HbO8
Heamoglobin + Oxygen Oxyhaemoglobin
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Learning Outcome
Describe and explain the characteristics of
enzyme catalysis, including
(I) specificity(using a simple lock and key
model) and the idea of competitive inhibition
(ii) structural integrity in relation to
denaturation and non-competitive inhibition.
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Enzyme catalysis Specific behavior to catalyse one particular reaction.
Mostly water soluble
Globular(ball-shaped) protein
Folding of protein creates channels and grooves in thesurface of the enzyme.
Substrate and enzyme molecules come in contact and
interact over only a small region of the enzyme surface.This region of interaction is called the active site.
Enzymes catalyze biochemical reactions and thusincrease the rate by provided an alternative pathway withlower activation.
The influence of enzyme on the rates of reactionsessential to life is amazing. An example is to remove CO2(a waste product of cellular respiration) out of the body bycarbonic anhydrase.
CO2 + H2O p H2CO3
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The binding of a substrate molecule to the active site of an enzymemay occur through hydrophobic attraction, hydrogen bonding,and/or ionic bonding. The complex formed when substrate andenzyme bond is called the enzymesubstrate (ES) complex. Oncethis complex is formed, the conversion of substrate (S) to product
(P) may take place:
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Lock and key model, enzymes surfaces will accommodateonly those substrates having specific shapes and sizes. Thus
only specific substrates that fit a given enzyme can formcomplexes with it.
Example
Sucrose + sucrase p Sucrase p Glucose + Sucrase-sucrose complex + Fructose
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A competitive inhibitor binds to the active site of an enzymeand thus competes with substrate molecules for the active
site. Competitive inhibitors often have molecular structures thatare similar to the normal substrate of the enzyme.
The effectiveness of the enzyme depends on the relativeconcentrations of the substrate and inhibitor molecules.
E.g a competitive inhibition of succinate dehydrogenase bymalonate which has similar structure to succinate. Succinate
dehydrogenase catalyzes the oxidation of the substratesuccinate to form fumarate by transferring two hydrogens tothe coenzyme FAD:
Competitive inhibition
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Extent of competitive inhibition
The conc. Of the substrate
The conc. Of the inhibitor
The bond strength between the active siteand the substrate
The bond strength between the active site
and the inhibitor
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Noncompetitive inhibitor
A noncompetitive inhibitor bears no resemblance to thenormal enzyme substrate, and binds reversibly to the surface
of an enzyme at a site other than the catalytically active site.The interaction between the enzyme and the noncompetitiveinhibitor causes the three-dimensional shape of the enzymeand its active site to change. The enzyme does not bind asnormal substrate in catalyzing the reaction.
Unlike competitive inhibition, noncompetitive inhibitioncannot be reversed by the addition of more substrate because
additional substrate has no effect on the enzyme-boundinhibitor (it cant displace the inhibitor because it cant bond tothe site occupied by the inhibitor).
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Extent of non-competitive
inhibition The conc. Of the inhibitor The affinity of the enzyme for the inhibitor.
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A variety of drug therapies make use of enzyme control to
selectively affect target cells.
A drug design can create a molecule which binds to onlyone type of enzyme, blocks normal catalysis and causesenzyme inhibition. The following example, a specific enzyme
is inhibited, which in turn causes a selective metabolicchange.
1. Methotrexate is an anticancer drug because it is similar instructure but different in function as coenzyme dihydrofolate.This coenzyme is needed to reproduce cellular geneticmaterial. When methotrexate replaces dihydrofolate, anenzyme is inhibited and genetic replication is slowed. Sincerapid cell growth requires genetic replication, rapidly growingcancer cells are selectively impacted by methotrexate
treatment.
Use of enzyme in biological system
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The Denaturation of proteins.
This is the disruption of the protein (secondary, tertiary, and
quaternary) structure by the breaking of the non-covalent( but
including disulph
ide bridges) interactions th
ath
old th
esestructures in their native conformation.
Protein function depends absolutely on its structure.. In denaturation,
the peptide bonds are not affected, but the hydrogen bonds,
disulfide bonds, ionic bonds and non polarinteractions can all be
disrupted.
There are five ways in which denaturation can occur
Mild reducing agents which can disrupt disulphide bridges
Changes in pH
Changes in temperature The presence of urea (a polar molecule) or other similar
molecules which disrupts specific hydrogen bonds
Specific metal ions which can disrupt the van der Waals forces
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When the pH of a solution containing protein is changed, the
protonation state of the amino and carboxylate groups
changes, and ionic bonds in the proteins will be disrupted.
If the pH is outside the 3-9
range then the protein structure canbe permanently destroyed. If the pH is lowered greatly, the
proteins will only contain positive charges. Like charges repel
each other and cause the denaturation of proteins . Likewise for
high pH. Hence, affecting their solubility
Reducing agents can break disulfide bonds, leading to a loss of
structure. Oxidizing agents can create new disulfide bonds where
they don't belong. This is the process used in hair "permanents". Areducing agent is put on the hair to break existing disulfide bonds.
The hair is then arranged in a new conformation (curlers) and an
oxidizing agent is added to form new disulfide bonds to maintain
this new structure.
1) Reducing agents
2) Change in pH
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3) Change in temperature.
As temperature increases, the weakest intermolecular forces are broken
first. Van der Waals forces and then hydrogen bonds are disrupted more
easily than ionic bonds in the secondary, tertiary and quaternarystructures of proteins.
Increasing the temperature means these weak forces break up due to
the extreme vibration of the secondary and tertiary structures and
irreversible changes take place.
Most proteins become denatured and thus unfold at temperatures above
60oC.
4) Presence of heavy metal ions. Eg Ag+, Hg2+ , Cd2+, Pb2+
Heavy metal ions are positively charged. It competes with positively
groups for attraction with negatively charged groups. These can disrupt
the ionic bonds between some amino residues and can also effect the
disulphide bridges between cysteine residues. Resident metal ions may
also be displaced.
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The effect of temperature
Increase the speed of the molecules
The thermal stability of the enzyme and of
the substrate. The activation energy of the catalysed
reaction.
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Learning Outcome
Describe the double helical structure ofDNA in terms of a sugar-phosphate
backbone and attached bases( only
general structure in terms of block diagram
is required)
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DNA
Controls the passing of genetic informationfrom one generation to the next.
Synthesis of protein
The structure enabled our understandingof
Heredity
Plant and anima breeding
Genetic diseases
Identification of individuals by DNA
fingerprint43
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DNAThe structure of DNA, according to Watson and Crick, consists of two
polymeric strands of nucleotides in the form of a double helix, with both
nucleotide strands coiled around the same axis. Along each strand arealternate phosphate and deoxyribose units with one of the four bases
adenine, guanine, cytosine, or thymine attached to deoxyribose as a side
group. This is sugar-phosphate backbone and attached bases.
The double helix is held together by hydrogen bonds extending from the
base on one strand of the double helix to a complementary base on the
other strand. The structure of DNA has been likened to a ladder that has
been twisted into a double helix, with the rungs of the ladder kept
perpendicular to the twisted railings. The phosphate and deoxyribose
units alternate along the two railings of the ladder, and two nitrogen bases
form each rung of the ladder.
Phosphate PhosphateSugar Phosphate
Base
SugarSugar
BaseBase
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DNA double helix
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Learning Outcome Explain the significance of hydrogen-bonding in
the pairing of bases in DNA in relation to thereplication of genetic information.
The four possible basepairings, A-T, T-A, G-C, andC-G, adenine-thymine andguanine-cytosine base pairsattract each other byhydrogen bond and van derwaals . This pairing results in
A:T and G:C ratios of 1:1.
Note that if the sequence ofone strand is known, thesequence of the other strandcan be determined. The twoDNA polymers are said to becomplementary to each other.All things come good
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Learning Outcome
Explain in outline how DNA encodes for
the amino acid sequence of proteins with
reference to mRNA, tRNA and the
ribosome in translation and transcription.
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Replication
Replication is the biological process for duplicating
the DNA molecule where an exact copy of a DNAmolecule is produced.
The DNA structure of Watson and Crick holds thekey to replication; because of the complementarynature of DNAs nitrogen bases, adenine bonds only
to thymine and guanine only to cytosine. Nucleotides with complementary bases can
hydrogen-bond to each single strand of DNA andhence be incorporated into a new DNA double helix.Every double-stranded DNA molecule that isproduced contains one template strand and onenewly formed, complementary strand. This form ofDNA synthesis known as semiconservativereplication.
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The two helices
unwind, separating
at the hydrogen
bonds. Each strand
then serves as a
template,
recombining withthe proper
nucleotides to form
a new double-
stranded helix. The
newly synthesizedDNA strands are
shown in blue.
The two strands run in opposite directions (anti-
parallel).
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Transcription1.One of the main functions of DNA is to direct the synthesis
of ribonucleic acids (RNAs). The transfer of geneticinformation from DNA to a molecule of messenger RNA iscalled transciption.
2.DNA serves as the storehouse of genetic information,whereas RNA is used to process this information intoproteins. Three types of RNA are needed to produceproteins: ribosomal RNA (rRNA), messenger RNA (mRNA),
and transfer RNA (tRNA).3.More than 80% of the cellular RNA is ribosomal RNA.
Ribosomes are the sites for protein synthesis. It is thelargest molecule among the 3.
4.Messenger RNA carries genetic information from DNA to
the ribosomes. It is a template made from DNA and carriesthe code that directs the synthesis of proteins. The size ofmRNA varies according to the length of the polypeptidechain it will encode.
5.The primary function of tRNA is to bring amino acids to theribosomes during protein synthesis. It is the smallest
molecule among the 3.
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6. When the nucleotide sequence of one strand of DNA is transcribed into asingle strand of RNA, genetic information is copied from DNA to RNA.This transcription occurs in a complementary fashion and depends uponhydrogen bonded pairing between appropriate bases. Guanine (G) basein DNA transcribed to cytosine (C) in RNA, thymine (T) to adenine (A) and
A to uracil (the thymine like base which is found in RNA).
The sugar in RNAis ribose.
DNA RNA
A U
T A
G C
C G
After transcriptionis complete the newRNA separates fromits DNA template.
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Process of translation
53Elongation
initiation
Termination
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Genetic Code
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If one pair of bases coded for a
given amino acid. How many
possible amino acids would be
possible.
But there are 20 types of amino
acids.
What is the number of bases needed
to code for every amino acids?
Identify codes for start, and stop.
What amino acid sequence would the
following base code produce?
You may use abbreviations in your
answer.-AUGUCUAGAGACGGGUAA-
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Learning Outcome
Explain the chemistry of DNA mutationfrom provided data.
Discuss the genetic basis of disease(for
example, sickle cell anaemia) in terms ofaltered protein structure and function.
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1.Mutation is the change resulting in genetic orchromosomal changes whichhave an incorrect base
sequence on DNA during th
e replication process. Othercauses of mutation: any process that damages the DNA, forexample, UV light, gamma and x-ray radiation, cigarettesmoke, and other chemical compounds.
2.Changes in a base or base pairs sequence may alter theamino acid coding and may lead to change in the structure
and functioning of protein. However, not all changes arecritical. Remove a start and stop codon has seriousconsequences. Common types of genetic alterations includethe substitution or deletion of a base. Such cases lead tochange in the genetic code and causes misinformation to betranscribed from the DNA.
3.Examples of genetic disorders are sickle cell anaemia(changeof position of a.a.) or cystic fibrosis (deletion of a.a).
Mutations
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4 5 6 7 8 9
Normal HbA -Thr-Pro-Glu-Glu-Lys-Ala
Sickle cell HbS -Thr-Pro-Val-Glu-Lys-Ala
4.Sickle-shaped red blood cells arises from a singlemutation in the DNA for one of the haemoglobinchains (see primary protein). Sickle cells sticks
together, to form a long rod making it insoluble andmay clog the blood vessels.
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Cystic Fibrosis
Thalassemia is an inherited blood disorder in which the body makes toomuch hemoglobin, the protein in red blood cells that carries oxygen. Thedisorder results in excessive destruction of red blood cells and anemia.
Diabetes Mellitus (DM) is a group of chronic metabolic disordercharacterized by high blood sugar (glucose) levels because the body doesnot produce enough insulin or deficiency of insulin.
He He Phe His Lys
He He His Lys ..
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Learning Outcome
Outline in terms of the hydrolysis of ATP toADP + Pi, the provision of energy for the
cell.
Structure of ATP
and ADP
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Hydrolysis of ATP This nucleotide is synthesised in the mitochondria of the cell.
This molecule consists of 3 phosphate groups and covalentlybonded to ribose sugar. Another organic base is attached to it.
ATP hydrolysis is an exothermic reaction. The is a net gain duringthe bond breaking of the phosphate groups and water.
The high negative charge density associated with the three adjacentphosphate units of ATP also destabilizes the molecule, making it higherin energy. Hydrolysis removes some of these electrostatic repulsionsas well, liberating useful energy in the process.
The conversion of ATP to ADP is enzyme catalysed because of thehigh activation energy.
One glucose molecule produces 38 molecules of ATP.
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Understand why some metals areessential to life, be able to explain the
chemistry involved,e.g haemoglobin;
sodium and potassium in transmission of
nerve impulses, zinc as enzyme as
cofactor.
3 Zi f t
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3. Zinc as enzyme cofactor A cofactor is a non-protein chemical compound that is
bound tightly to an enzyme and is required for catalysis.
They can be considered "helper molecules/ions" that assistin biochemical transformations. Carbonic anhydrase, is one of the most efficient enzymes in
our red blood cells, it is responsible for the removal of carbondioxide from the blood, producing hydrogen carbonate ions.Zinc ion (Zn2+) reacts as cofactor of the enzyme. It bound to
the enzyme as part of a complex using nitrogen atoms on theprotein chain. Water is also bound to the zinc ion. Since the zinc ion has a
high charge density it assists the breakdown of this watermolecule into an H+ and an OH- ion. The hydroxide ion isthen in a position to attack the carbon dioxide molecule. The
product of this nucleophilic attack is the hydrogen carbonateion which is released from the active site.
CO2 + OHp HCO3
-
Following release of the hydrogen carbonate ion a furtherwater molecule binds to the zinc and the catalytic cyclebegins again.
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Other cofactors
Large organic molecules often provided by
vitamin .
Bind temporarily to the enzyme
Assist in the transfer of groups or
electrons not available within the active
site itself.
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Sodium Potassium Pump
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The hydrolysis is accomplished
by Na+ ,K+- ATPase
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Learning Outcome
Recognise that some metals are toxic and
discuss, in chemical terms, the problems
associated with heavy metals in the
environment entering the food chain, fore.g. mercury
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4. Problems associated with heavy metalHeavy metal ion poisoning
You are probably aware that compounds containing heavy
metals such as lead, mercury, copper or silver arepoisonous. This is because ions of these metals are non-competitive inhibitors for several enzymes.
1. E.g Silver ions react with -SH groups in the side groups ofcysteine residues in the protein chain:
2. The bond between silver and sulphur can be consideredas covalent since their difference of electronegativities is0.6 (2.5-1.9).
3. If the cysteine residue is on the protein chain, it mightaffects the tertiary structure and the shape of the activesite, then stop the enzyme from working.
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Mercury ions like silver ions may act as non-competitiveinhibitorthat may bind irreversibly to enzyme containingamino acids side-groups such as SH and COOH or discrupt
the disulphide bridge.This changes distort the shape of the enzyme so that theycannot carry out its function.The effects such as Minamata disease where 1,700people died after methyl mercury was released in wastewater.
The mercury accumulated in the food chain via shellfishand fish which were consumed by the local population.
The chemical action of mercury ions may be described as follows:
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Mercury can enter the food chain by a number of routes:1. in waste water discharged into rivers from factories(battery
manufacturer or gold extraction) that use mercury
compounds in their processes,2. mercury compounds have been used as fungicides andthese can be washed off crops into the soil,
3. mercury compounds have been used to treat timber or feltand again they can be washed into rivers and streams,
4. a mercury cathode cell is one which is used in the large
scale production of sodium hydroxide. However, theleakage of mercury is dangerous as micro-organisms canconvert mercury salts into organomercury compounds e.g.methylmercury salts, and these can be ingested by water-borne organisms. Here they accumulate and are passedthrough the food chain, via fish, for instance, and finish upin man.
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June 2008
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More information
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5 The primary function of tRNA is to bring amino acids to the
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5.The primary function of tRNA is to bring amino acids to theribosomes for incorporation into protein molecules.Consequently there exists at least one tRNA for each of the20 amino acids required for proteins. Transfer RNA
molecules have a number of structural features in common.a)The primary structure of tRNA allows extensive folding of
the molecule such that complementary bases are hydrogen-bonded to each other to form a structure that appears like acloverleaf.
b)The end of the chain of all tRNA molecules terminates in aCCA nucleotide sequence to which is attached the aminoacid to be transferred to a protein chain.
c)The cloverleaf model of tRNA has an anticodon loopconsisting of seven unpaired nucleotides. Three of thesenucleotides make up an anticodon. The anticodon iscomplementary to, and hydrogen-bonds with, three baseson an mRNA.
d)The other two loops in the cloverleaf structure enable thetRNA to bind to the ribosome and other specific enzymesduring protein synthesis.
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Translation1. Translation is a conversion process of the code
carried by mRNA into an amino acid sequence of a
protein.2. In the translation the mRNA serves as a template on
which amino acids are assembled in the proper sequencenecessary to produce the desired protein. This takesplace when the code or message carried by mRNA istranslated into an amino acid sequence by tRNA.
3. In summary of protein synthesis process.
a) DNA partially unwind (unzip) and transcribes its basesequences code to a shorter strand of RNA mRNA.
b) This moves out of the cell nucleus to the ribosomes.Amino acids are collected by transfer-RNA moleculescoded for a particular position on a m-RNA molecules andhence the correct sequence (primary structure) isassured.
DNA RNA ProteinTranscription Translation
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Aspartic acid, 2-aminobutanedioic acid, residue Aspwhich with alkali,
HOOCCH2CH(NH-)CO- + OH- -OOCCH2CH(NH-)CO- + H2O
so increase in pH (more alkaline) could disrupt a hydrogen bond involving the
HOOC group,
or with acid, -OOCCH2CH(NH-)CO- + H+ HOOCCH2CH(NH-)CO-
so decrease in pH could disrupt an important ionic bond.
The red - covalent bond connects the peptide CO/NH link of the nextamino acid residue, the polypeptide linkage between two residues is NH-CO
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Metals in biological system
1. Iron in haemoglobin
Iron is an essential component of haemoglobin, transporting oxygen inthe blood to all parts of the body. It also plays a vital role in manymetabolic reactions. Iron deficiency can cause anaemia resulting fromlow levels of haemoglobin in the blood.
Functions
Iron is essential for the formation of haemoglobin, the red pigment in
blood. The iron in haemoglobin combines with oxygen and transports itthrough the blood to the body's tissues and organs.
2. Sodium and potassium in transmission of nerve impulses
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p p The ionic composition within living cells is different from that of their
surroundings.Within cells the Na+ ion concentration is lower, andthe K+ ion concentration higher, than the surrounding liquid
outside. When a nerve is stimulated sodium ions pour into the nerve cell. Whenthis signal has passed the Na+ and K+ ion concentrations have to berestored to normal by the sodium being transported out of the cell onceagain. The energy to drive this transport come from the hydrolysis ofATP assisted by an enzyme often referred to as the sodium-potassiumpump.
These enzyme molecules are located in the cell membrane. They sitacross the membrane with parts of the protein exposed on the outerand inner surfaces (they are trans-membrane proteins).
Initially three Na+ ions and an ATP molecule bind to the inner proteinsurface of the enzyme. The ATP is then hydrolysed, with the Pi bindingto the protein. The enzyme changes shape so that the Na+ ions moveto the outside surface. Here they are released and two K+ ions attach tothe protein instead. The release of the phosphate group from theenzyme results in the K+ ions moving into the cell. When a new ATPmolecule attaches to the enzyme, the K+ ions are released inside thecell and the cycle of transport can begin again. Thus the ATP-drivensodium-potassium pump restores the concentrations of K+ and Na+ to
their normal levels following a nerve impulse.
The maintenance of ion balance in cells, and the generation and
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The maintenance of ion balance in cells, and the generation andtransmission of electrical impulses, does not solely depend on ATP-dependent ion pumps. There are also specific water and ionchannels that have been identified in cell membranes. These arealso protein structures but the energy required and their selectivity is
dependent on the hydration and size of the ions concerned. Thepotassium specific channel has been worked on in detail and theexplanation found as to why K+ ions, and not the smaller Na+ ionsare allowed through the channel. The key lies in the fact that theaqueous K+ ions (K+(aq)) must lose their hydration shells before theycan pass through the channel. The K+ (aq) ions are stripped of theassociated water molecules as they enter the channel, linking
instead to oxygen atoms in certain R-groups of the protein. The enthalpy required to lose the hydration shell around the ions is
compensated for by that given out when the new association isformed with the protein. The K+ ions pass through the channel andthen re-associate with water on the other side. The hydration shell isre-formed around the ion and energy is released. The selectivity ofthe channel depends on the distances between the oxygen atoms inthe protein side-chains and the K+ ions. The smaller Na+ ions will notfit the channels as the distances are too great for the complex toform.
Diabetes and other serious diseases of the nervous system,muscles, and heart can be attributed to malfunctioning cellular waterand ion channels.
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5. Cystic fibrosis affects the lungs, pancreas, gut and sweat
glands due to secretion of a thick sticky mucous forms
that block the supply of enzymes as in the case of the
pancreas or cavities and tube inside the lung. This is dueto the malfunctioning of the CFTR protein (cystic fibrosis
transmembrane regulatory protein) that do not allow
chloride ions in the cell to leave. The osmotic pressure in
the cell increases and draws water into the cell instead.
Hence the mucus lining of the cell become thicken.
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An example of an
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An example of anenzyme that contains acofactor is carbonic
anhydrase and isshown in the ribbondiagram with a zinccofactor bound in itsactive site.
These tightly-boundmolecules are usuallyfound in the active siteand are involved incatalysis reaction. Thegrey sphere is the zinccofactor in the activesite.
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June 2007
Primar Protein
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Primary ProteinThe human insulin consist of two chains having a total of51 amino acid residues. In the molecule, there are twodisulfide bridges that hold the chains together and onedisulfide linkage within a chain.
Insulin serves an essential role in regulating the use ofglucose by cells. Inadequate production of insulin leads todiabetes mellitus, and people with severe diabetes must
take insulin shots.
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- chain
F- chain