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Write a short essay on biological buffer systems and how they operate.Definition and relevance A buffer is an aqueous system that tends to resist changes in pH when small amounts of acids (H+) or base (OH-) are added.  These systems consist of a conjugate acid pair ; usually a weak acid (proton do...

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Write a short essay on biological buffer systems and how they operate.

Definition and relevance  A buffer is an aqueous system that tends to resist changes in pH when small amounts of acids (H+) or base (OH-) are added .  These systems consist of a conjugate acid pair ; usually a weak acid (proton donor ) and its conjugate base ( proton acceptor ).  Biological processes are predominantly pH dependent , meaning that a small change in this parameter can lead to larger changes in the rate of the process .  This is true for reactions which directly and indirectly involve the H+ ion.  The protonated amino and carboxyl groups of amino acids and the phosphate groups of nucleotides for example function as weak acids , with their ionic state determined by the pH of the surrounding medium.  Phosphate , bicarbonate and ammonia are main biolgocial buffering systems Henderson Hasselbach Equation  The fact that the titration curves of NH4+ and H2PO4- have near identical shapes suggests that these curves reflect a fundamental law or relationship .  This equation is important to understand buffer action and acid base balance in the blood and tissues.

Bicarbonate and ammonia buffering systems  pH of this buffering system depends on cenentrationof H2CO3 and HCO3- ( proton donor and acceptor )  near pH of 7.4 , H2Co3 of blood plasma is in equilbiirum with a large nerve capacity of Co2 in the air space of the lungs. Urinary buffer - -ammonia . Glutamine metabolism generates NH4+. Its secretion also generates “new” bicarbonate 

Diabetes  Blood plasma usually 7.35 -7.45 .  Diabetes mellitus , lack of insulin or hypersensitivity , disrupts uptake of glucose into tissues and forces to use stored fatty acids as fuel (B hydroxybutric acid and acetoacetic acid formed – ketoacidosis )  Alkosis of the blood can also occur.

Provide three different examples of stereoisomerism found in biomolecular structures

Intro • Stereochemistry: concerned with issues arising from the 3D nature of pharmaceuticals • Stereoisomers: same atom-to-atom connectivity, different orientation in 3D space • Cis/trans , D/L and epimers and anomers are all types of steroisomerism found in biomoleular structures .

Enantiomers D/L  Enantiomers – stereoisomers which are nonsuperimposable mirror images of each other  R/S system analogous to D/L , except D/L system is used specifically for amino acids.  Determined by the priority of the substituent at chiral centre (alpha carbon) , ranking based on atomic no of atoms by the Cahn Ingold Prelog sequence series  Amino acid residues in protein molecules are exclusively L stereoisomers , D stereosiomers have been found in a few small peptides eg found in bacterial cell walls and peptide antibiotics.

 Absolute configuration is determined by comparison with the absolute configuration of 3-carboned glyceraldehyde

Diastereoisomers • Diastereoisomers: stereoisomers which are not enantiomers • Are different chemical entities • Different physical properties, separate chromatographically, not the same chemical entities Cis /trans – E/Z Geometrical isomers differ in the spatial position around a carbon-carbon double bond due to restricted rotation. If same groups are placed on same side of the double bonded carbon atom, it is known as a cis-isomer. If

the same groups are placed on opposite sides of the double bonded carbon atom, it is known as a transisomer. Trans and cis-isomers show different physical and chemical properties like melting point, boiling point and other chemical reactions(3) Maleate is cis isomer and fumarate is trans isomer; each is a well-defined compound that can be separated from the other, and each has its own unique chemical properties. A binding site (on an enzyme ,for example) that is complementary to one of these molecules would not be complementary to the other, which explains why the two compounds have distinct biological roles despite their similar chemistry.

Cis and trans retinal

Epimers

 Two sugars that differ only in the configuration about one carbon are called epimers.

Describe the characteristic properties of the amino acid L-histidine Category

 Histidine is categorized as an amino acid with a positively charged R group; an aromatic imidazole group.  It may charged or uncharged at pH 7 due to be being the only common amino acid with a side chain of pKa (-log10Ka) of near neutrality.  As a result of this His residues facilitate a variety of enzyme catalysed reactions by serving as proton donors/acceptors.

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Tautomerism The ability of certain organic compounds to react in isomeric structures that differ from each other in the position of a hydrogen atom and a double bond. Tautomerism - N1 - N3 pKa of imidazole – 7.0 pKa in AA – 6.0 In proteins pKa is ~ 6-7.6 Small change in pH alters protonation state

Protonated His+: •Tautomerism H-N1+ and H-N3+ •Important in acid-base catalysis •His acts as proton shuttle

Imidazole/histidine When it is protonated, histidine can act as a general acid during catalysis, donating its proton to the substrate. When deprotonated, histidine can act as a general base. One family of enzymes, the ribonucleases, hydrolyze the phosphodiester bonds in RNA. A

key part of their catalytic machinery in a pair of histidines, one of which is protonated and one that is not. The latter acts as a base, and the former acts as an acid, in a mechanism that utilizes both acid and base catalysis.

Imidazole –H+ / histidine – H+ Isoelectric point of Histidine 7.47- the characteristic pH at which the net charge is zero. Another function of histidine is as a ligand for metal ions. Many enzymes use metal ions for catalysis, and contain a set of ligands that coordinate to the metal ion in order to hold it in place in the active site. Ligands must be able to function as Lewis bases, which are atoms that can donate electrons. The nitrogen atoms of the imidazole ring of histidine make it a

good Lewis base, so it is good at coordinating to metal ions and is frequently found in metalloenzymes. 4. Write a short essay on open chain and cyclic structures of monosaccharides.

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Definition Monosaccharides consist of a single polyhydroxy aldehyde or ketone unit . The most abundant monosaccharide in nature is the six carbon sugar D gluocose (dextrose ) . Monosaccharides of four of more carbons tend to have cyclic structures. These have chiral centres and their abosulte configurations are known by x-ray crystallography . Both Fischer and Haworth projections can be used to represent these structures.

Ketoses and aldoses  IN THE OPEN CHAIN FORM one carbonyl group – all remaining carbons are hydroxylated.  Aldose – carbonyl at end of carbon chain  Ketose – carbonyl not at end of carbon chain Names derived from number of carbons in chain eg Triose (3), tetrose (4), pentose (5), hexose (6), heptose (7) 

 Hexoses are the most common monosacchardies found in nature and key intermediates in the central energy yielding reactions in most organisms.

Ketones can be converted to aldoses eg dihydroxyacetone phosphate to glyceraldehydes 3 phosphate by the action of triose phosphate isomerase

Cyclic structure  In aqueous solution all monosaccharides and aldotetroses with five or more atoms in the carbon backbone occur predominatly as cyclic structures , carbonyl group formed covalent bond with the oxygen group of a hydroxyl group along the chain.  Six membered pyranoses - pyran.  Aldohexoses such as glucose can also exist in cyclic fivemembered rings that resemble furan, but this is not as stable as the pyranose.  Ketohexoses only form 5-membered furanose rings  Ring formation creates another chiral carbon about the hemiacetal or hemiketal anomeric carbon.  For 6- membered glucose rings the α anomer has the -OH projecting down, the β anomer has the -OH projecting upward.  Mutarotation – a and beta anomers of D – glucose interconvert , in which one ring form opne into the linear form briefly then closes to produce the B anomer.

Glyscosides • Treatment of a monosaccharide hemiacetal with an alcohol (R-OH) and an acid catalyst yields an acetal in which the anomeric –OH has been replaced by an –OR group • Glycoside • Stable to neutral bacic (rel. mild) conditions • Are not in equilibrium with open chain form • Do not show mutarotation • Converted back to monosaccharide with dilute acid. • Beta d glucopyransose – H+/-H20 – salicin

Saccharides  Phosphorylation - condensation with phosphoric acid to form a sugar ester (e.g. glucose-6-phosphate). This activates the sugar for subsequent transformation.  Acetylation, eg. at C2 - N-acetly glucosamine, N-acetyl galactosamine).  Amination - eg. - glucosamine, galactosamine, mannosamine  N-acetyl glucosamine (C2)  Oxidation/carboxylation  Sulfonation (heparan), etc.

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. Describe the process of ionisation of water and its main parameters and relationships.

Introduction  Eventhough most of the the solvent properties ofo water are explain with reference to the uncharged water molecule it is vitl that the small degree of ionsiatio of water to OH- and H+ ions isi taken itno account.  The total hydrogen ion concentration si experimentally masurabke and is expressed as the pH of the soulktion (log10[H+] / -log10[H3O+] Pure water is slightly ionised  Free protons do not exist in solution , hydrated H+ ions are hydronium ions.  The strong hydrogen bonding affinity of water molecules makes this process virtually instantaneous  Ionisation measured by electrical conductivity ( H3O+ to cathode and OH- to anode) Proton hopping  No individual proton moves very far from bulk solution , series of proton hops between the H- bonded water molecules causes the net movement of a proton over a long distance in a shirt time.)OH- moves in th same way but in the opposite direction.

 Ionic product of water pH scale Kw is the basis for the pH scale.  Neutrality at & derived from Kw at 250C.  Glass electrode this is selectively sensitive to H+ concentrations but insensitive to Na+ and K+ and other cations . pH meter – signal from the electrode is amplified and compared with signal generated by a solution of accurately known pH.  Metabolic alkalosis – adrenal disease and lung disease can bring no respiratory alkalosis. Conjugate acid base pairs.  Behaviour of biological acids and bases in water  Acid dissociation constant  Stronger the tendency to dissociate a proton the stronger is the acid and lower pKa . pKa of water itself is H2) is 16) Flo eg  Pka – pH when 50% of the substance is ionised , midpoint of titration curve for acid or base

2. Write an essay on the common secondary structures found in proteins describing their characteristic features.

 Introduction  Secondary structure refers to any chosen segement of a polypwptide chain and describes the local spatial arrangement of its main chain atoms without regard ot the positioning of its side chains or relationship to other segments.  Regular 2structure – when phi and psi remain the same or nearly the same throughout the segement.  

The four atoms making up φ are a carbonyl carbon, the connecting αcarbon, an amide nitrogen and the next carbonyl carbon – phi The four atoms which constitute a ψ are an amide nitrogen, a carbonyl carbon, an α-carbon and a second nitrogen- psi

Alpha helix

 Simplest conformation that a polypeptide can adopt.  The polypeptide backbone wound tightly around an imaginary axis 5Å in diameter, R’s stick outwards at an angle from the axis.  10 – 40 AA (shorter more stable)  Although both R- and L-handed helices are possible, only Rhanded are observed in the cell.

 The C=O is bonded to the NH : i + 4  i AA (towards the Cterminus)  The repeating unit of a single helical turn occurs every 5.4Å.  Some AAs occur with greater frequency: eg. Glu, Met and Ala  Infrequently occurring: eg. Pro, Gly certain combinations together eg. bulky or similarly charged residues spaced four apart multiple sequential Glu or Lys.

Beta sheets  Zigzagging PP chains arranged in parallel Tend to be quite short involving 5-8 consecutive residues.  H-bonding occurs between back bone atoms in adjacent strands either within the same polypeptide chain or between different polypeptide chains.  Adjacent chains can be either parallel or antiparallel with respect to amino  carboxyl orientations  Significant part of protein structure is non-oriented (random coil) Diagrams

Turns and Loops  In globular proteins turns and loops REVERSE the direction of a polypeptide chain, helping it adopt a more compact shape β- Turns Involve 4 amino acid residues  The C=O of the first residue forms a H-bond with H-N of the fourth residue  often involve Gly and Pro (6% of peptide bonds involving proline are in the cis configuration.  found near the surface of proteins, interacting with H2O

Recurring principles of protein structure 1.The 3D structure of a protein is determined by its amino acid sequence. 2.The function of a protein depends on its 3D structure. 3.An isolated protein usually exists as one or a small number of structural forms (thermodynamically most favorable). 4.The most important forces stabilizing protein structure are noncovalent interactions. 5.Many proteins contain common structural patterns (motifs, sequence homologies). Alpha keratin – fibrous protein found in hair and nails Silk fibroin – B conformation – rich in Ala and Gly residues

5. Write a short essay on adenosine triphosphate (ATP) as the main energy currency of the cell.

 Introduction  Adenosine triphosphate is a coenzyme which classified as a purine and is sometimes referred to "molecular unit of currency" of intracellular energy transfer.  The plasma membrane is impermeable to organic molecules with phosphate groups , trapping ATP inside cells to serve as the universal energy carrier of cell metabolism.

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Mechanism Cells require chemical energy for three general types of tasks: to drive metabolic reactions that would not occur automatically; to transport needed substances across membranes; and to do mechanical work, such as moving muscles. ATP is not a storage molecule for chemical energy; that is the job of carbohydrates, such as glycogen, and fats. When energy is needed by the cell, it is converted from storage molecules into ATP.

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ATP then serves as a shuttle, delivering energy to places within the cell where energy-consuming activities are taking place.

Structure  2 phosphoanyhdride and 1 phosphoester bond  ATP is a nucleotide that consists of three main structures: the nitrogenous base, adenine; the sugar, ribose; and a chain of three phosphate groups bound to ribose.  The phosphate tail of ATP is the actual power source which the cell taps.  Available energy is contained in the bonds between the phosphates and is released when they are broken, which occurs through the addition of a water molecule (a process called hydrolysis).  Usually only the outer phosphate is removed from ATP to yield energy; when this occurs ATP is converted to adenosine diphosphate (ADP), the form of the nucleotide having only two phosphates.

 Phosphorylation  ATP is able to power cellular processes by transferring a phosphate group to another molecule (a process called phosphorylation).  This transfer is carried out by enzymes eg phosphatases and kinases that couple the release of energy from ATP to cellular activities that require energy. Production  Although cells continuously break down ATP to obtain energy, ATP also is constantly being synthesized from ADP and phosphate through the processes of cellular respiration.  Most of the ATP in cells is produced by the enzyme ATP synthase, which converts ADP and phosphate to ATP.  ATP synthase is located in the membrane of cellular structures called mitochondria; in plant cells, the enzyme also is found in chloroplasts.

3. Write an essay on the four common nucleotide bases that compose ribonucleic acids.

Introduction  Uracil , adenine , cytosine and guanine are all found in RNA  The nitrogenous bases are derivatives of two parent compounds purine (adenine and guanine ) and pyrmidine ( cytosine and uracil ) .  These bases are heterocyclic compounds.

Uracil

cytosine

Adenine Structure in nucleotide

Guanine

 Base is joined covalently in a N- beta – glycosyl bond to the 1’ carbon of the pentose , and the phosphate is esterified to the 5’ carbon. The N – beta – glycosyl bond is formed by removal of the elements of water as in O – glycosidic bond formation . Adenine  Nucleobases" are the parts of RNA and DNA that are involved in pairing up.  Adenine forms two hydrogen bonds with uracil in RNA  The structure of adenine is critical, in that having only two sites for hydrogen bonding, it binds only to thymine (and uracil in RNA), while cytosine, which has three sites for hydrogen bonding, binds only to guanine.  These four "code letters" allow cells to store their blueprint about how that life form is built.  The manner in which these hydrogen bonds hold the strands of the nucleic acid together to form the double helix, yet allow the strands to "unzip" for replication and transcription, is remarkable from a design point of view.  All cells of all living organisms, no matter how simple or complex, share this design. 

In the human body, adenine is synthesized in the liver and changes to adenosine when combined with ribose.

Uracil

 Uracil is also a component of several coenzymes that act in conjunction with enzymes in several processes of carbohydrate metabolism Guanine 

Guanine binds to cytosine through three hydrogen bonds.

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In cytosine, the amino group acts as the hydrogen donor and the C-2 carbonyl and the N-3 amine as the hydrogen-bond acceptors.

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Guanine has a group at C-6 that acts as the hydrogen acceptor, while the group at N-1 and the amino group at C-2 acts as the hydrogen donors.

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Guanine has two tautomeric forms: the keto form (characterized by an attached OH group) and the enol form (characterized by an attached CH2 group).

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Guanine can be hydrolyzed with strong acid at 180°C to glycine, ammonia, carbon dioxide, and carbon monoxide. Guanine oxidizes more readily than adenine, the other purine-derivative base in DNA and RNA. Its high melting point of 350°C reflects the strong intermolecular hydrogen bonding between the oxo and amino groups in the molecules in the crystal

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. Because of this intermolecular bonding, guanine is relatively insoluble in water, although it is soluble in dilute acids and bases

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Cytosine can also be a part of a nucleotide other than related to DNA or RNA. As cytidine triphosphate (CTP), it can act as a co-factor to enzymes, and can transfer a phosphate to convert adenosine diphosphate (ADP) to adenosine triphosphate (ATP

4. Describe the main groups of lipids. Discuss their common and distinctive features using examples.

Intro

 Lipids are a chemically diverse class of biomolecules characterized by their insolubility in H2O  That means lipids are generally NON-POLAR and HYDROPHOBIC  some lipids, however, are AMPHIPATHIC (part of the molecule is polar and part is non-polar) They are generated primarily from fatty acids

Fatty Acids • Fatty acids are carboxylic acids with hydrocarbon chains • Saturated fatty acids DO NOT contain carbon-carbon double bonds • Unsaturated fatty acids contain carbon-carbon double bonds (C=C) • Cellular oxidation of fatty acids to CO2 and H2O is highly exergo...