Key Chemical Concepts Related To Health Science

Part A

1. 1-hexanamine has a linear chain while triethylamine has a branched structure. Boiling point increases for a linear chain; more compact and branching structures exhibit less interaction between molecules, thereby having less Vander Waals forces of interaction as in case of triethylamine. More spread structure causes boiling point to rise in 1-hexanamine (Salammal et al., 2015).
2. The chemical structure of Propanol has a highly polar OH group which takes part in hydrogen bonding and its highly electronegative oxygen with lone pairs of electrons contribute to permanent dipole-dipole interactions.Propanal with CHO functional group lacks the hydrogen bonding interactions as the highly electronegative oxygen atom is bonded to carbon, only dipole-dipole interactions result. Vander Waals forces of attractions are present in both propanol and propanal (Cunningham et al., 2018). Higher number of intermolecular forces contributes to higher boiling point (97°C) in propanol compared to propanal (48°C).
3. The difference in melting point of fatty acids depends on the molecular weight and the extent of unsaturation. Stearic acid is a saturated fatty acidwith a linear structure. Linoleic acid has two unsaturated double bonds positioned at 9 and 12 respectively. Higher the number of unsaturation, lower will be the melting point of the fatty acid. Linoleic acid with 2 double bonds has a spherical non-linear structurewith less intermolecular interaction. Resultant decreased Vander Waals forces lower the melting point of Linoleic acid (Budin et al., 2014).
4. Amides have a functional group CONH2, which performs antibacterial activity by causing membrane disruption for gram-positive and gram-negative bacteria(Pérez-Peinadoet al., 2018). The amides and derivatives target the thick peptidoglycan layer in gram-positive bacteria and outer polysaccharide layer in gram-negative bacteria causing permeabilization and inhibition of peptidoglycan synthesis.

Amides are synthesized in derivatives to augment the antibacterial activities of bactericidal agents in response to evolving bacterial infections. They are used as beta-lactam targets and enzyme inhibitors to dissolve the bacterial cell membrane and inhibit both DNA and RNA synthesis.

Biological systems are composed of fundamental units of life termed as cells, whose structure and function rely on the carbon containing biomolecules: Carbohydrates, Proteins, Lipids and Nucleic acids. The complex structure of biomolecules are related to the diverse functions they perform in the living systems.

Carbohydrates serves as one of the major energy sources for living systems. Depending on the structural units, carbohydrates are classified into three classes namely:

Monosaccharides:The monosaccharides comprise of the simple sugars like glucose and fructose. They have a short chain length ranging from three to six carbon atoms. They are highly soluble in water and cannot be further broken down. Glucose is the most abundant monosaccharide found in living system and major metabolic byproduct. Monosaccharides are again classified into aldoses and ketoses based on the presence of oxidized functional group. Glucose is an aldose sugar with aldehyde as the functional group while dihroxyacetone is a ketose sugar with carbonyl group (Voet, Voet &Pratt, 2016).

Oligosaccharides:Monosaccharides are joined together through covalent linkage called glycosidic bonds to synthesize short chains varying between two to ten monosaccharide units. These short chains are termed as oligosaccharides which are easily hydrolysable into their constituent monosaccharides. Oligosaccharides are further classified depending on the number of linking monosaccharide units. These are classified as follows:

• Disaccharides:These are composed of two units of monosaccharides. Lactose is a disaccharide composed of glucose and galactose monosaccharides.
• Trisaccharides:These comprise of three units of linked monosaccharides. Raffinose is a trisaccharide consisting of alpha galactosyl derivatives of sucrose.
• Tetrasaccharides:These contain four units of monosaccharides linked together. Stachyose is a tetrasaccharide which hydrolyzes into one unit each of glucose and fructose and two units of galactose.

Polysaccharides: These comprise of thousands of monosaccharide units linked through glycosidic bonds. Polysaccharides are insoluble in water but soluble in organic solvents. Polysaccharides with one type of constituent monosaccharide are termed as homopolysaccharides whereas those with more than one type of monosaccharide unit are heteropolysaccharides (Lundblad & MacDonald, 2018).Cellulose is a plant homopolysaccharide with glucose as the constituent unit.Hyaluronic acid composed of glucuronic acid and N-acetyl glucosamine is a heteropolysaccharide found in synovial fluid of joints.

Proteins play a pivotal role in relation to genetic synthesis. Understanding their levels of structural organization help elucidate their functional roles in living systems.Proteins organize into four fundamental structures which are as follows:

Primary Structure:The sequence of universally occurring twenty amino acids connected by peptide bonds in the polypeptide chain forms the primary structure of proteins. Different arrangements of the amino acids in the polypeptide generates a huge diversity among proteins. The amino acids vary in the side chains which confer differing chemical, physical and structural properties to the peptide (Kennedy et al., 2016). This amino acid sequence is encoded into the genetic machinery (DNA) which is transcribed and translated to synthesize proteins. These proteins undergo modifications to become biologically active inside cells.

Secondary Structure:The polypeptide chains form conformations through hydrogen bonding into structures called alpha-helix and beta-sheet. Alpha helices are right handed coiled coil structure with amino acid side chains protruding outward. Alpha helices are stabilized by hydrogen bonding interactions (Rahal & Waltz, 2018). Beta sheets are composed of either parallel (both strands are N to C terminus) or antiparallel (N to C terminus for strand and vice-versa for the other) strands stabilized by inter-strand hydrogen bonds. The antiparallel beta sheets occur as the most stable form of secondary structure due to less steric hindrance.

Equilibrium Constant Expression

Tertiary Structure:Polypeptides fold into random three dimensional shape to remain in the lowest energy state achieving maximum stability. Under physiological pH, the non-polar amino acids are buried inside the interior with the polar acidic and basic amino acids facing the outer hydrophilic aqueous environment.Covalent disulphide bridges, ionic interactions and salt bridge interactions stabilize the folding of polypeptide chains. The biological activities rely on the tertiary structure of proteins.

Quaternary Structure: The identical or different protein subunits arrange and aggregate into a native protein structure giving rise to its quaternary structure. They undergo conformational alterations to promote biological activity. The subunits are stabilized by interchain disulphide bonds, salt bridge interactions and hydrogen bonds (Dey & Levy, 2018).

Lipids comprise almost half of the membrane structure forming lipid bilayers. A lipid bilayer is essential to maintain the fluidic nature of cell membranes. Phospholipids are the most abundant form of lipids in bilayer formation, undergoing a change of phase from liquid to crystalline states termed as phase transition. Presence of unsaturation and shorter carbon chains lowers the temperature of phase transition, as a result the membrane remains in fluidic state. Cholesterol, glycolipids and inositol phosphates are commonly present in the membrane, important roles lying in cell signaling (Laganowsky et al., 2014). Sphingolipids remain concentrated into microdomains called lipid rafts through transient attractive forces. Lipid rafts also contain cholesterol; a common occurrence in animal cells membranes (Sezgin et al., 2017).Phosphatidylcholine and sphingomyelin are located in the outer leaflet while phosphatidylserine and phosphatidylethanolamine localize in the inner leaflet. The functional importance of asymmetry in phospholipid distribution in bilayer lies in the binding of cytosolic proteins to the lipid head groupsin response to extracellular signaling cascades.Lipid kinases bind and phosphorylate inositol phosphates activating the respective membrane transport proteins. Glycolipids are found in the outer leaflet of the cell membrane and function in calcium-mediated neural signalling. They serve a crucial role in cell recognition and immune response. Differing concentrations of membrane glycolipids lead to lysosomal storage disorders as well as diseases of CNS.

1. Cyanide anion blocks cellular respiration by inhibiting cytochrome c oxidase in mitochondria.

Mechanism of inhibition:Cyanide acts as a non-competitive inhibitor and binds irreversibly to a site other than the enzyme active site, thereby blocking the prosthetic group iron and inhibiting cytochrome c oxidasenormal activity.Increasing the substrate concentration does not reverse the inhibition.

Effect of inhibition:Cytochome c oxidase is involved in the electron transport chain transferring electrons to produce ATP in mitochondria. Inhibition results in hindrance of electron transfer. This results in dramatic reduction in ATP production blocking cellular respiration.

1. DNA strand 1     3′- TAAAATCAGCTCTAGACGGTACTCTACTAGTCATGGTCCATG- 5′

mRNA               3’-UAAAAUCAGCUCUAGACGGUACUCUACUAGUCAUGGUCCAUG-5’

Translation would be as follows:

5’-3’ Frame 1: Stop-NQL-Stop-TVLY-Stop-SWS-met

5’-3’ Frame 2: KISSRRYSTSHGP

5’-3’ Frame 3: KSALDGTLLVMetVH

3’-5’ Frame 1: HGP-Stop-LVEYRLELIL

3’-5’ Frame 2: MetDHD-Stop-Stop-STV-Stop-S-Stop-F

3’-5’ Frame 3: WTMetTSRVPSRADF

DNA strand 2    3′- AGGACGTAGCTTTTAACGCTCTAAAGGAAATTA- 5′

mRNA              3’-AGGACGUAGCUUUUAACGUCUAAAGGAAAUUA-5’

Translation would be as follows:

5’-3’ Frame 1: RT-Stop-LLTL-Stop-RKL

5’-3’ Frame 2: GRSF-Stop_RSKGN

5’-3’ Frame 3: DVAFNALKEI

3’-5’ Frame 1: Stop-FPLEL-Stop-KLRP

3’-5’ Frame 2: NFL-Stop-SVKSYV

3’-5’ Frame 3: ISFRALKATS

1. Normal DNA strand      5’-C A C G T G G A C T G A G G A C T C C T C T T C-3’

Sequence of the mRNA    3’-G U G C A C C U G A C U C C U G A G G A G A A G-5’

K Values

Sickle cell DNA         5’-C A C G T G G A C T G A G G A C A C C T C T T C-3’

Sequence of sickle mRNA 3’-G U G C A C C U G A C U C C U G U G G A G A A G-5’

CTC codon codes for leucine in normal strand which is replaced by codon CAC coding histidine. This will not affect the hemoglobin role in carrying oxygen. Glutamate substituted for valine results in hydrophobic patch formation, as a result hemoglobin cannot bind oxygen. Leucin to histidine substitution will not affect hemoglobin role of carrying oxygen.

4a. Adenine is aconstituent of both DNA and RNA.

4b. Guanine is present in both DNA and RNA.

4c. 2-deoxy-D-ribose is present only in DNA.

4d. Cytosine occurs in both DNA and RNA.

4e. Thymine is present only in DNA.

4f. D-ribose occurs in RNA and DNA.

4g. Uracil occurs as a component of RNA in place of thymine in DNA.

1. Human DVEKGKKIFIM

Rhesus monkey DVEKGKKIFIM

Bullfrog             DVEKGKKIFVQ

Tuna                  DVAKGKKTFVQ

Chicken             DIEKGKKIFVQ

Silkworm moth NAENGKKIFVQ

Amino acid sequence similarity shows the evolutionary relationship. Amino acid sequence is unique to a given species; similarity among species shows the origin from a common ancestor.Amino acid sequence of rhesus monkey is identical to that of human, revealing their common ancestry. Differences in the amino acid sequence shows a likelihood being close relatives to the human species, as is observed for the above species.

6a. The coding strand is 5′ – ATGGACGGTTGA – 3′.

The template strand is 3′ – TACCTGCCAACT – 5′.

6b. The sequence of mRNA after transcription is 5’-AUGGACGGUUGA-3’.

6c. 5’AUG3’ is the initiator codon for translation, fMet tRNA with anticodon sequence 3’UAC5’ will initiate translation. The respective anticodons of tRNA are 3’CUG5’, 3’CCA5’ and 3’ACU5’.

6d. The protein sequence after translation is as follows:

5’-3’ Frame 1: Met-DG-Stop

5’-3’ Frame 2: WTV

5’-3’ Frame 3: GRL

3’-5’ Frame 1: STVH

3’-5’ Frame 2: QPS

3’-5’ Frame 3: NRP

References:

Bettleheim, I., Prywes, N., Zhang, N., & Szostak, J. W. (2014). Chain-length heterogeneity allows for the assembly of fatty acid vesicles in dilute solutions. Biophysical journal, 107(7), 1582-1590.

Cunningham, W. P., Xia, I., Wickline, K., Garcia Huitron, E. I., & Heo, J. (2018). Studying Intermolecular Forces with a Dual Gas Chromatography and Boiling Point Investigation. Journal of Chemical Education, 95(2), 300-304.

Dey, S., & Levy, E. D. (2018). Inferring and Using Protein Quaternary Structure Information from Crystallographic Data. In Protein Complex Assembly (pp. 357-375). Humana Press, New York, NY.

Kennedy, E., Dong, Z., Tennant, C., & Timp, G. (2016). Reading the primary structure of a protein with 0.07 nm 3 resolution using a subnanometre-diameter pore. Nature nanotechnology, 11(11), 968.

Laganowsky, A., Reading, E., Allison, T. M., Ulmschneider, M. B., Degiacomi, M. T., Baldwin, A. J., & Robinson, C. V. (2014). Membrane proteins bind lipids selectively to modulate their structure and function. Nature, 510(7503), 172.

Lundblad, R. L., & Macdonald, F. (Eds.). (2018). Handbook of biochemistry and molecular biology. CRC Press.

Pérez-Peinado, C., Dias, S. A., Domingues, M. M., Benfield, A. H., Freire, J. M., Rádis-Baptista, G., … & Veiga, A. S. (2018). Mechanisms of bacterial membrane permeabilization by crotalicidin (Ctn) and its fragment Ctn (15–34), antimicrobial peptides from rattlesnake venom. Journal of Biological Chemistry, 293(5), 1536-1549.

Rahal, I., & Walz, J. (2018). Secondary protein structure prediction combining protein structural class, relative surface accessibility, and contact number. International Journal of Data Science, 3(1), 68-85.

Salammal, S. T., Dai, S., Pietsch, U., Grigorian, S., Koenen, N., Scherf, U., … & Brinkmann, M. (2015). Influence of alkyl side chain length on the in-plane stacking of room temperature and low temperature cast poly (3-alkylthiophene) thin films. European Polymer Journal, 67, 199-212.

Voet, D., Voet, J. G., Pratt, C., & BIOCHEMISTRY, F. O. (2016). Life at the molecularlevel.