CHEMISTRY OF LIFE

CHM 1313 Centre of Pre-U Studies

Content
Protein chemistry Genetic information Energy Metals in biological systems

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 be illustrated 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 the chemistry of given examples.
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Learning Outcomes
Recall that proteins are condensation polymers formed from amino-acid monomers and recognise and describe the generalised structure of amino acids

Proteins
A protein chain will have somewhere in the range of 50 to 2000 2-amino acid residues. Every protein has a similar backbone of carbon and nitrogen atoms held together by peptide bonds:

protein backbone (in box)

-CCNCCNCCNCCNCC-

The proteins are difference in the length of the backbone and the sequence of the side chains (R groups) that are attached to the backbone.
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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 the chemistry learnt in the core syllabus.
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Primary Protein
refer to the linear sequence of amino acid and as such has an amino terminal end and a carboxy terminal end. Each different protein in a biological organism has a unique sequence of amino acid residues. The sequence that causes a protein chain to fold and curl into the distinctive shape and enables the protein to function properly. Only covalent bonds exist.

Primary structure of the enzyme lysozyme found in hen egg white

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Secondary Protein
1.Secondary protein structure is refer when the chain can be rotated 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-coiled spring that is stabilised by hydrogen bonds between carbonyl oxygen and amide hydrogen. The carbonyl group of each amino acid is hydrogen-bonded to the amide hydrogen of the four amino acid in the chain. The sequence of amino acids is important because the groups that form side-chains in a protein can interact with other side chains further along the chains as it bends.(see tertiary structure)
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.

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 are pointing 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. 10

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 sheet In a beta-pleated sheet,. A secondary protein structure in which the chains are folded so that they lie alongside each other held together by hydrogen bonds. 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 the 2amino acid residues in the protein. The tertiary structure results from interactions between the R side chains of the amino acid residues. These R-group interactions are of four types: 1. Disulfide bridges: As in the structure of insulin, a disulfide linkage can form between two cysteine residues that are close to each other in the same chain or between cysteine residues in different chains. 2. Salt bridges: These interactions are a result of ionic bonds that 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 nonpolar phenyl rings.

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Tertiary structure
Refers to its 3-dimensional structure of the polypeptide. is a description of the way the whole chain (including the secondary structures) folds itself into its final 3-dimensional shape. The tertiary structure of a protein is held together by interactions between the side chains - the "R" groups. There are several ways this can happen.
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1) Ionic bonds between charged R groups

Between 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, =NR groups)

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3. Van der Waals forces between non-polar molecules

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.

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4) Sulphur bridges
It 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 pleated sheets are shown The disulphide bridges are shown by purple atoms bonded together. 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 are called 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 transports round 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 carbon and 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 of 6 because the central metal ion is forming 6 co-ordinate bonds. 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 the haemoglobin. 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 Oxyhaemoglobin
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Heamoglobin + Oxygen

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 the surface 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 thus increase the rate by provided an alternative pathway with lower activation. The influence of enzyme on the rates of reactions essential to life is amazing. An example is to remove CO2 (a waste product of cellular respiration) out of the body by carbonic anhydrase. CO2 + H2O p H2CO3 28

The binding of a substrate molecule to the active site of an enzyme may occur through hydrophobic attraction, hydrogen bonding, and/or ionic bonding. The complex formed when substrate and enzyme bond is called the enzymesubstrate (ES) complex. Once this 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 accommodate only those substrates having specific shapes and sizes. Thus only specific substrates that fit a given enzyme can form complexes with it.

Example

Sucrose + sucrase p Sucrase p Glucose + Sucrase -sucrose complex + Fructose

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Competitive inhibition A competitive inhibitor binds to the active site of an enzyme and thus competes with substrate molecules for the active site. Competitive inhibitors often have molecular structures that are similar to the normal substrate of the enzyme. The effectiveness of the enzyme depends on the relative concentrations of the substrate and inhibitor molecules. E.g a competitive inhibition of succinate dehydrogenase by malonate which has similar structure to succinate. Succinate dehydrogenase catalyzes the oxidation of the substrate succinate to form fumarate by transferring two hydrogens to the coenzyme FAD:

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Extent of competitive inhibition

The conc. Of the substrate The conc. Of the inhibitor The bond strength between the active site and 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 the normal 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 noncompetitive inhibitor causes the three-dimensional shape of the enzyme and its active site to change. The enzyme does not bind as normal substrate in catalyzing the reaction. Unlike competitive inhibition, noncompetitive inhibition cannot be reversed by the addition of more substrate because additional substrate has no effect on the enzyme-bound inhibitor (it cant displace the inhibitor because it cant bond to the 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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Use of enzyme in biological system

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 only one type of enzyme, blocks normal catalysis and causes enzyme inhibition. The following example, a specific enzyme is inhibited, which in turn causes a selective metabolic change. 1. Methotrexate is an anticancer drug because it is similar in structure but different in function as coenzyme dihydrofolate. This coenzyme is needed to reproduce cellular genetic material. When methotrexate replaces dihydrofolate, an enzyme is inhibited and genetic replication is slowed. Since rapid cell growth requires genetic replication, rapidly growing cancer cells are selectively impacted by methotrexate 35 treatment.

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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 disulphide bridges) interactions that hold these structures 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 polar interactions 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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1) Reducing agents
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". A reducing 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.

2) Change in pH
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 can be 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
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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 quaternary structures 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 of DNA 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 information from one generation to the next. Synthesis of protein The structure enabled our understanding of
Heredity Plant and anima breeding Genetic diseases Identification of individuals by DNA fingerprint
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DNA
The 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 are alternate 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. Base Base Base

Phosphate

Sugar

Phosphate

Sugar

Phosphate

Sugar

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 44 form each rung of the ladder.

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 the replication of genetic information.
The four possible base pairings, A-T, T-A, G-C, and C-G, adenine-thymine and guanine-cytosine base pairs attract each other by hydrogen bond and van der waals . This pairing results in A:T and G:C ratios of 1:1. Note that if the sequence of one strand is known, the sequence of the other strand can be determined. The two DNA polymers are said to be complementary to each other.
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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 DNA molecule is produced. The DNA structure of Watson and Crick holds the key to replication; because of the complementary nature 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 and hence be incorporated into a new DNA double helix. Every double-stranded DNA molecule that is produced contains one template strand and one newly formed, complementary strand. This form of DNA synthesis known as semiconservative replication.
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The two helices unwind, separating at the hydrogen bonds. Each strand then serves as a template, recombining with the proper nucleotides to form a new doublestranded helix. The newly synthesized DNA strands are shown in blue.
The two strands run in opposite directions (antiparallel).
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1. One of the main functions of DNA is to direct the synthesis of ribonucleic acids (RNAs). The transfer of genetic information from DNA to a molecule of messenger RNA is called transciption. 2. DNA serves as the storehouse of genetic information, whereas RNA is used to process this information into proteins. Three types of RNA are needed to produce proteins: 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 the largest molecule among the 3. 4. Messenger RNA carries genetic information from DNA to the ribosomes. It is a template made from DNA and carries the code that directs the synthesis of proteins. The size of mRNA varies according to the length of the polypeptide chain it will encode. 5. The primary function of tRNA is to bring amino acids to the ribosomes during protein synthesis. It is the smallest 51 molecule among the 3.

Transcription

6. When the nucleotide sequence of one strand of DNA is transcribed into a single strand of RNA, genetic information is copied from DNA to RNA. This transcription occurs in a complementary fashion and depends upon hydrogen bonded pairing between appropriate bases. Guanine (G) base in 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 RNA is ribose.  DNA RNA AU TA GC CG  After transcription is complete the new RNA separates from its DNA template.
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Process of translation
initiation

Termination

Elongation

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Genetic Code
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 mutation from provided data. Discuss the genetic basis of disease(for example, sickle cell anaemia) in terms of altered protein structure and function.

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Mutations
1. Mutation is the change resulting in genetic or chromosomal changes which have an incorrect base sequence on DNA during the replication process. Other causes of mutation: any process that damages the DNA, for example, UV light, gamma and x-ray radiation, cigarette smoke, and other chemical compounds. 2. Changes in a base or base pairs sequence may alter the amino acid coding and may lead to change in the structure and functioning of protein. However, not all changes are critical. Remove a start and stop codon has serious consequences. Common types of genetic alterations include the substitution or deletion of a base. Such cases lead to change in the genetic code and causes misinformation to be transcribed from the DNA. 3. Examples of genetic disorders are sickle cell anaemia(change of position of a.a.) or cystic fibrosis (deletion of a.a).

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4. Sickle-shaped red blood cells arises from a single mutation in the DNA for one of the haemoglobin chains (see primary protein). Sickle cells sticks together, to form a long rod making it insoluble and may clog the blood vessels. Normal HbA Sickle cell HbS 4 5 6 7 8 9 -Thr-Pro-Glu-Glu-Lys-Ala -Thr-Pro-Val-Glu-Lys-Ala

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He He

He He

Phe His

His Lys ..

Lys

Cystic Fibrosis

Thalassemia is an inherited blood disorder in which the body makes too much hemoglobin, the protein in red blood cells that carries oxygen. The disorder results in excessive destruction of red blood cells and anemia. Diabetes Mellitus (DM) is a group of chronic metabolic disorder characterized by high blood sugar (glucose) levels because the body does not produce enough insulin or deficiency of insulin.

Learning Outcome
Outline in terms of the hydrolysis of ATP to ADP + Pi, the provision of energy for the cell.

Structure of ATP and ADP

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 This nucleotide is synthesised in the mitochondria of the cell. This molecule consists of 3 phosphate groups and covalently bonded to ribose sugar. Another organic base is attached to it. ATP hydrolysis is an exothermic reaction. The is a net gain during the bond breaking of the phosphate groups and water. The high negative charge density associated with the three adjacent phosphate units of ATP also destabilizes the molecule, making it higher in energy. Hydrolysis removes some of these electrostatic repulsions as well, liberating useful energy in the process. The conversion of ATP to ADP is enzyme catalysed because of the high activation energy. One glucose molecule produces 38 molecules of ATP.

Hydrolysis of ATP

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 Understand why some metals are essential 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.

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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 assist in biochemical transformations. Carbonic anhydrase, is one of the most efficient enzymes in our red blood cells, it is responsible for the removal of carbon dioxide 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 the protein chain. Water is also bound to the zinc ion. Since the zinc ion has a high charge density it assists the breakdown of this water molecule into an H+ and an OH- ion. The hydroxide ion is then in a position to attack the carbon dioxide molecule. The product of this nucleophilic attack is the hydrogen carbonate ion which is released from the active site. CO2 + OH p HCO3 Following release of the hydrogen carbonate ion a further water molecule binds to the zinc and the catalytic cycle 63 begins again.

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

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, for e.g. mercury

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4. Problems associated with heavy metal

Heavy metal ion poisoning You are probably aware that compounds containing heavy metals such as lead, mercury, copper or silver are poisonous. This is because ions of these metals are noncompetitive inhibitors for several enzymes. 1. E.g Silver ions react with -SH groups in the side groups of cysteine residues in the protein chain:

2. 3.

The bond between silver and sulphur can be considered as covalent since their difference of electronegativities is 0.6 (2.5-1.9). If the cysteine residue is on the protein chain, it might affects the tertiary structure and the shape of the active site, then stop the enzyme from working. 67

Mercury ions like silver ions may act as non-competitive inhibitor that may bind irreversibly to enzyme containing amino acids side-groups such as SH and COOH or discrupt the disulphide bridge. This changes distort the shape of the enzyme so that they cannot carry out its function. The effects such as Minamata disease where 1,700 people died after methyl mercury was released in waste water. The mercury accumulated in the food chain via shellfish and 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 and these can be washed off crops into the soil, 3. mercury compounds have been used to treat timber or felt and 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, the leakage of mercury is dangerous as micro-organisms can convert mercury salts into organomercury compounds e.g. methylmercury salts, and these can be ingested by waterborne organisms. Here they accumulate and are passed through the food chain, via fish, for instance, and finish up in man.

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More information

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5. The primary function of tRNA is to bring amino acids to the ribosomes for incorporation into protein molecules. Consequently there exists at least one tRNA for each of the 20 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 hydrogenbonded to each other to form a structure that appears like a cloverleaf. b)The end of the chain of all tRNA molecules terminates in a CCA nucleotide sequence to which is attached the amino acid to be transferred to a protein chain. c)The cloverleaf model of tRNA has an anticodon loop consisting of seven unpaired nucleotides. Three of these nucleotides make up an anticodon. The anticodon is complementary to, and hydrogen-bonds with, three bases on an mRNA. d)The other two loops in the cloverleaf structure enable the tRNA to bind to the ribosome and other specific enzymes during protein synthesis. 73

Translation
1. 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 sequence necessary to produce the desired protein. This takes place when the code or message carried by mRNA is translated into an amino acid sequence by tRNA. 3. In summary of protein synthesis process. a) DNA partially unwind (unzip) and transcribes its base sequences 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 molecules coded for a particular position on a m-RNA molecules and hence the correct sequence (primary structure) is assured. DNA Transcription RNA Translation Protein
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Aspartic acid, 2-aminobutanedioic acid, residue Asp which with alkali, HOOCCH2CH(NH-)CO- + OH-OOCCH 2CH(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 next amino 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 in the blood to all parts of the body. It also plays a vital role in many metabolic reactions. Iron deficiency can cause anaemia resulting from low 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 it through the blood to the body's tissues and organs.

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2. Sodium and potassium in transmission of nerve impulses

The ionic composition within living cells is different from that of their surroundings. Within cells the Na+ ion concentration is lower, and the K+ ion concentration higher, than the surrounding liquid outside. When a nerve is stimulated sodium ions pour into the nerve cell. When this signal has passed the Na+ and K+ ion concentrations have to be restored to normal by the sodium being transported out of the cell once again. The energy to drive this transport come from the hydrolysis of ATP assisted by an enzyme often referred to as the sodium-potassium pump. These enzyme molecules are located in the cell membrane. They sit across the membrane with parts of the protein exposed on the outer and inner surfaces (they are trans-membrane proteins). Initially three Na+ ions and an ATP molecule bind to the inner protein surface of the enzyme. The ATP is then hydrolysed, with the Pi binding to the protein. The enzyme changes shape so that the Na+ ions move to the outside surface. Here they are released and two K+ ions attach to the protein instead. The release of the phosphate group from the enzyme results in the K+ ions moving into the cell. When a new ATP molecule attaches to the enzyme, the K+ ions are released inside the cell and the cycle of transport can begin again. Thus the ATP-driven sodium-potassium pump restores the concentrations of K+ and Na+ to78 their normal levels following a nerve impulse.

 The maintenance of ion balance in cells, and the generation and transmission of electrical impulses, does not solely depend on ATPdependent ion pumps. There are also specific water and ion channels that have been identified in cell membranes. These are also protein structures but the energy required and their selectivity is dependent on the hydration and size of the ions concerned. The potassium specific channel has been worked on in detail and the explanation found as to why K+ ions, and not the smaller Na+ ions are allowed through the channel. The key lies in the fact that the aqueous K+ ions (K+(aq)) must lose their hydration shells before they can pass through the channel. The K+ (aq) ions are stripped of the associated 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 is formed with the protein. The K+ ions pass through the channel and then re-associate with water on the other side. The hydration shell is re-formed around the ion and energy is released. The selectivity of the channel depends on the distances between the oxygen atoms in the protein side-chains and the K+ ions. The smaller Na+ ions will not fit the channels as the distances are too great for the complex to form. Diabetes and other serious diseases of the nervous system, muscles, and heart can be attributed to malfunctioning cellular water and ion channels. 79

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 due to 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 enzyme that contains a cofactor is carbonic anhydrase and is shown in the ribbon diagram with a zinc cofactor bound in its active site. These tightly-bound molecules are usually found in the active site and are involved in catalysis reaction. The grey sphere is the zinc cofactor in the active site.
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Primary Protein
The human insulin consist of two chains having a total of 51 amino acid residues. In the molecule, there are two disulfide bridges that hold the chains together and one disulfide linkage within a chain. Insulin serves an essential role in regulating the use of glucose by cells. Inadequate production of insulin leads to diabetes mellitus, and people with severe diabetes must take insulin shots.
- chain

F- chain

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