chemistry of life-student

8/3/2019 Chemistry of Life-student

1/83

CHEMISTRY OF LIFE

CHM 1313

Centre of Pre-U Studies

1


2/83

2

Content

Protein chemistry

Genetic information

Energy Metals in biological systems


3/83

3

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.


4/83

4

Learning Outcomes

Recall that proteins are condensation

polymers formed from amino-acid

monomers and recognise and describe thegeneralised structure of amino acids


5/83

5

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-


6/83

6

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.


7/83

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


8/83

8

Primary structure of the enzyme lysozyme found in hen egg white


9/83

9

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


10/83

10

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.


11/83

11

Proline is an amino acid that does not form an

alpha helix because of its cyclic structure, the

structure becomes destabilised.


12/83

12

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


13/83

13

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.


14/83

14

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

+).


15/83

15

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.


16/83

16

June 2008


17/83


18/83

18

1) Ionic bonds between charged R

groupsBetween two oppositively charged side

chains(e.g Aspartic acid and Lysine)

usually groups that ionise in water


19/83

19

2) Hydrogen bonds between polar

R groups

Between polar side chains(-OH, -NH,=O, =NRgroups)


20/83

20

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


21/83

21

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


22/83

22

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".


23/83

23

Quaternary Structure of Proteins

A protein which contains two polypeptides

chains that combine. The example shown

is haemoglobin


24/83

24

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.


25/83

25

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.


26/83

26

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


27/83

27

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.


28/83

28

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


29/83

29

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:


30/83

30

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


31/83

31

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


32/83

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

32


33/83

33

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).


34/83

Extent of non-competitive

inhibition The conc. Of the inhibitor The affinity of the enzyme for the inhibitor.

34


35/83

35

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


36/83

36


37/83

37


38/83

38

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


39/83

39

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


40/83

40

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.


41/83

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.

41


42/83

42

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)


43/83

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


44/83

44

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


45/83

DNA double helix

45


46/83

46

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


47/83

47


48/83

48

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.


49/83

49

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.


50/83

50

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).


51/83

51

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.


52/83

52

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.


53/83

Process of translation

53Elongation

initiation

Termination


54/83

Genetic Code

54

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-


55/83

55


56/83

56

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.


57/83

57

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


58/83

58

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.


59/83

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 ..


60/83

60

Learning Outcome

Outline in terms of the hydrolysis of ATP toADP + Pi, the provision of energy for the

cell.

Structure of ATP

and ADP


61/83

61

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.


62/83

62

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


63/83

63

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.


64/83

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.

64


65/83

Sodium Potassium Pump

65

The hydrolysis is accomplished

by Na+ ,K+- ATPase


66/83

66

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


67/83

67

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.


68/83

68

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:


69/83

69

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.


70/83

70

June 2008


71/83

More information

71


72/83

72

5 The primary function of tRNA is to bring amino acids to the


73/83

73

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.

T l ti


74/83

74

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


75/83

75

June 2007


76/83

76

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

M t l i bi l i l t


77/83

77

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


78/83

78

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


79/83

79

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.

5 C ti fib i ff t th l t d t


80/83

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.

80

An example of an


81/83

81

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.


82/83

82

June 2007

Primar Protein


83/83

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.

83

- chain

F- chain

chemistry of life-student

Documents