Macromolecules and importance of key biological processes
Biological processes are controlled and fuelled by Macromolecules. Structural change of any sort either genetically or during the life of an individual, such as diet can have drastic consequences on the life expectancy of the cell. Macromolecules to consider are proteins which are important for growth and repair, lipids protect the cell membrane and are a dense energy storage, carbohydrates are basically used for energy storage of the cell. Deoxyribonucleic acid and Ribonucleic acid, code for the characteristic of the organism and aids expression characteristics of the cell respectively.
Sickle cell Anaemia
Sickle cell disease is acquired by an abnormal form of the ?-globin gene called sickle haemoglobin (Hb S). |It is Inherited in an autosomal recessive fashion, meaning an individual can possess either two copies of Hb S or one copy of Hb S including another ?-globin form such as Hb C for disease expression. Sickle cell haemoglobin carriers are protected from malaria infection, and this protection probably led to the high frequency of Hb S in individuals of African ancestry. In spite of the evolutionary advantage, persons with sickle cell disease display severe morbidity and mortality rate. Symptoms consist of chronic anaemia, acute chest syndrome, stroke, splenic and renal dysfunction, pain crises, and susceptibility to bacterial infections. Pediatric mortality is primarily due to bacterial infection and stroke. In recent years, newborn screening, better medical care, parent education, and penicillin prophylaxis have successfully reduced morbidity and mortality due to Hb S. (Ashley-Koch, Yang and Olney, 2000). Thus, malaria has imposed extreme selective pressure on the human genome, far more than any other infectious disease, and the RBC has been the prime target for evolutionary adaptation. These mutations are prime examples of Haldane’s notion of “balanced polymorphism,” in which genes are fixed at a high frequency in susceptible populations because the enhanced fitness enjoyed by heterozygotes more than outweighs the morbidity and mortality suffered by homozygotes or compound heterozygotes (Bunn, 2012).
Central Dogma of Molecular Biology
The Central Dogma of molecular biology was proposed by crick in 1958, it describes the flow of genetic information in cells from DNA to messenger RNA (mRNA) to protein. Information stored in DNA is so central to cellular function, therefore, the cell keeps the DNA protected in the nucleus and copies it in the form of RNA. The translation of this information to a protein is more complex because three mRNA nucleotides correspond to one amino acid in the polypeptide sequence.
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. During transcription, a DNA sequence is read by RNA polymerase, which produces a complementary, antiparallel RNA strand. Transcription is the first step in gene expression. If the transcribed gene encodes a protein, the result of transcription is messenger RNA (mRNA), which will then be used to create that protein in the process of translation.
Translation is the process by which mRNA is decoded and translated to produce a polypeptide sequence, otherwise known as a protein. This method of synthesizing proteins is directed by the mRNA and accomplished with the help of a large complex of ribosomal RNAs (rRNAs) and proteins. Transfer RNA (tRNA), translates the sequence of codons on the mRNA strand. The main function of tRNA is to transfer a free amino acid from the cytoplasm to a ribosome, where it is attached to the growing polypeptide chain. The ribosome then releases the completed protein into the cell (Courses.lumenlearning.com, 2017).
Haemoglobin and Sickle cell Haemoglobin
The table below shows the mutations leading to qualitative alterations in haemoglobin, the missense mutation in the ?-globin gene that causes sickle cell anaemia is the most common. The mutation causing sickle cell anaemia is a single nucleotide substitution (A to T) in the codon for amino acid 6. The change converts a glutamic acid codon (GAG) to a valine codon (GTG).The underlying problem in sickle cell anaemia is that the valine for glutamic acid substitution results in haemoglobin tetramers that aggregate into arrays upon deoxygenation in the tissues. This aggregation leads to deformation of the red blood cell into a sickle-like shape making it relatively inflexible and unable to traverse the capillary beds. This structural alteration in the red blood cell can easily be seen under light microscopy and is the source of the name of this disease. Repeated cycles of oxygenation and deoxygenation lead to irreversible sickling (King, 2017).
Sickle cell Haemoglobin (Hbs)
Normal Haemoglobin (Hb)
Sickle Cell Haemoglobin
Deoxyribonucleic acid and Ribonucleic acid
DNA, or deoxyribonucleic acid, is like a blueprint of biological guidelines that a living organism must follow to exist and remain functional. RNA, or ribonucleic acid, helps carry out this blueprint’s guidelines. RNA is more versatile than DNA, capable of performing numerous, diverse tasks in an organism, but DNA is more stable and holds more complex information for longer periods of time. DNA is found in the nucleus of a cell (nuclear DNA) and in mitochondria (mitochondrial DNA). It has two nucleotide strands which consist of its phosphate group, a five-carbon sugar (the stable 2-deoxyribose), and four nitrogen-containing nucleobases: adenine, thymine, cytosine, and guanine.
During transcription, RNA, a single-stranded, linear molecule, is formed. It is complementary to DNA, helping to carry out the tasks directed by the DNA. Like DNA, RNA is composed of its phosphate group, a five-carbon sugar (the less stable ribose), and four nitrogen-containing nucleobases: adenine, uracil (not thymine), guanine, and cytosine. In both molecules, the nucleobases are attached to their sugar-phosphate backbone. Each nucleobase on a nucleotide strand of DNA attaches to its partner nucleobase on a second strand: adenine links to thymine, and cytosine links to guanine. This linking causes DNA’s two strands to twist and wind around each other, forming a variety of shapes, such as the famous double helix (DNA’s “relaxed” form), circles, and supercoils.
In RNA, adenine and uracil (not thymine) link together, while cytosine still links to guanine. As a single-stranded molecule, RNA folds in on itself to link up its nucleobases, though not all become partnered. These subsequent three-dimensional shapes, the most common of which is the hairpin loop, help determine what role the RNA molecule is to play as messenger RNA (mRNA), transfer RNA (tRNA), or ribosomal RNA (rRNA) (Diffen.com, n.d.).
Semiconservative Replication of DNA and Storage
The semiconservative replication model states that two original DNA strands, that is the two complementary halves of the double helix separate during replication. Each strand then serves as a template for a new DNA strand, which means that each newly synthesized double helix is a combination of one original and one new DNA strand which is produced naturally in the body by an enzyme called polymerase. The complementary nature and the fact that adenine always pairs with thymine and cytosine always pairs with guanine makes the semiconservative model plausible (Pray, 2008).
Throughout most of the life of a cell, the DNA is only loosely wrapped around the histones and is not in the condensed chromosomal form. The condensing of chromosomes occurs only during mitosis, the process of cell division. During mitosis, the chromosomes condense so that each chromosome is a distinct unit. If the chromosomes do not line up properly, severe genetic abnormalities can occur, which can lead to the death of the cell or cancer. Condensing the DNA into tightly packed chromosomes makes the process of chromosome alignment and separation during mitosis more efficient (Thompson, 2017).
Arginine is essential amino acid and is a positively charged. Arginine is well designed to bind the phosphate anion, it is often found in the active centres of proteins that bind phosphorylated substrates such as the DNA since it is negatively charged. As a cation, arginine, as well as lysine, plays a role in maintaining the overall charge balance of a protein (Biology.arizona.edu, 2003).
Chromosomal behaviour during meiosis in relation to sickle anaemia
Equal lengths of chromatids of the same homologous pair break off and crossed over. This stage is called the recombinant stage in meiosis 1. This is important as it ensures variation within a species to produce adaptable characteristics over time to ensure posterity of the human race (Bbc.co.uk, 2014)
Inherited characteristics are encoded in the DNA in segments called genes also known as Mendel factor. Genes occur in pairs called alleles. They occupy the same physical positions on homologous chromosomes.The expression of the trait that results in the physical appearance of an organism is called the phenotype in contrast to the genotype, which is the actual genetic constitution.The alleles do not always express themselves equally; one trait can mask the expression of the other. The masking factor is the dominant trait, the masked the recessive.If both alleles for a trait are the same in an individual, the individual is homozygous for the trait and can be either homozygous dominant or homozygous recessive. If the alleles are different that is, one is dominant, the other recessive the individual is heterozygous for the trait. Crosses between parents that differ in a single gene pair are called monohybrid crosses (Hb Hb and Hbs Hbs) produces individuals with the sickle cell traits, but not with no symptom of the disease. Some alleles are both expressed in the same phenotype, a situation called codominance (Bbc.co.uk, 2017) (Cliffsnotes.com, 2016).
Characteristic structures of Macromolecules
Triglycerides are made up of 3 fatty acid chains attached to a glycerol molecule. Fatty acids are chains of carbon atoms, the terminal one having an OOH group attached making a carboxylic group (COOH).Three of these chains become attached to a glycerol molecule which has 3 OH groups attached to its 3 carbons. This is called a condensation reaction because 3 water molecules are formed from 3 OH groups from the fatty acids chains and 3 H atoms from the glycerol. The bond between the fatty acid chain and the glycerol is called an ester bond.The 3 fatty acids may be identical or they may have different structures (S-cool.co.uk, 2016).
A phospholipid is composed of two fatty acids, a polar molecule, a glycerol unit, and a fatty acid which is displaced by a phosphate group (ThoughtCo, 2017).
Most carbohydrates are polysaccharides, a ?-glucose is a hexose monosaccharide because of the position of the OH group in the compound. Monosaccharides are linked together by glycosidic bonds. During synthesis, a hydrogen atom on one monosaccharide bonds to a hydroxyl (OH) group on the other, releasing a molecule of water, this is a condensation reaction which produces ?1-4 glycosidic bond from hexose sugars. The reverse of this synthesis reaction is hydrolysis; a molecule of water reacts with the glycosidic bond breaking it apart. A starch is a mixture of two polysaccharides of ?-glucose. Amylose is a type of starch made up of long unbranched chains of ?-glucose (Burrows et al., 2015).
Proteins are polymers made from monomer units of Amino acid. Bonds between amino acids are called peptide bonds. A compound formed by bonding two amino acids is called a condensation reaction. Hence a compound made of many amino acids bonded together is called a polypeptide. There are 20 amino acids; there are 12 amino acids the body can produce, hence there are non-essential. While the essential amino acid are those the body can not produce and there are 8 in number. Amino acids are mainly made of 3 functional groups a carboxylic acid (-COOH), an Amino group (-NH2) and an R group. The polypeptide can have four different levels of structure primary 10, secondary 20, Tertiary 30, and quarternary 40. Proteins come in two formats, structural and globular. If the ?-pleated sheet predominates in the protein, it is a structural protein example are keratin, collagen, actin and myosin. On another hand, if the ?-helix predominates in the protein it is a globular protein and all enzymes are globular proteins examples are Haemoglobin and Amylose (Variatch, 2017).
The fluid mosaic model describes the structure of a cell membrane. It describes that the cell membrane is not solid. The plasma membrane is a mosaic of phospholipids, cholesterol molecules, proteins and carbohydrates. Phospholipids make up the basic structure of a cell membrane. A single phospholipid molecule has two different ends. The head end contains a phosphate group and is hydrophilic. This means that it is attracted to water molecules. The tail end is made up of two strings of hydrogen and carbon atoms called fatty acid chains. These chains are hydrophobic and do not like to associate with water molecules.The phospholipids of a cell membrane are arranged in a double layer called the lipid bilayer. The hydrophilic phosphate heads are always arranged so that they are near water. The hydrophobic tails of membrane phospholipids are organized in a manner that keeps them away from water. Cholesterol molecules are important for maintaining the consistency of the cell membrane. Membrane proteins function as enzymes to speed up chemical reactions, act as receptors for specific molecules, or transport materials across the cell membrane.
Carbohydrates are sometimes found attached to proteins or lipids as glycoproteins or glycolipids and are only found in the extracellular matrix of the cell membrane.Together, these carbohydrates form the glycocalyx. The glycocalyx of a cell has many functions. Based on the structure and types of carbohydrates in the glycocalyx, your body can identify cells and determine if they should be there or not. It can also act as a glue to attach cells together (Study.com2017).
Enzymes and functions
Enzymes function by lowering the activation energy needed to make a chemical reaction occur. Like other catalysts, enzymes change the equilibrium of a reaction but do not get used up in the process. A crucial characteristic of an enzyme is its specificity.
Two explanations of how enzymes interact with substrates are the “lock and key” model, proposed by Fischer in 1894. The induced fit model is a modification of the lock and key model that was proposed by Daniel Koshland in 1958. In the lock and key model, the enzyme and the substrate have three-dimensional shapes that fit each other. Nevertheless, the induced fit model proposes that enzyme molecules can change their shape on interaction with the substrate in this model. The enzyme and sometimes the substrate change shape as they interact until the active site is fully bound (Helmenstine, 2017).
Globular Proteins are enzymes molecule which forms a coiled shape. The hydrophobic groups point into the centre of molecule away from water. Only hydrophilic groups are exposed outside the molecule so globular proteins are soluble. Haemoglobin is an example of globular protein where the 3D shape of the protein is crucial binds to oxygen to transport it around body.like in the sickle cell anaemia where one change has a radical in changing the shape and reduces its ability to bind to oxygen
Fibrous Proteins are Polypeptides which form long chains running parallel to each other.These chains are linked by disulphide cross bridges making the proteins very stable and strong. Fibrous proteins have structural functions: Keratin in skin and hair and Collagen is found in bone, cartilage, tendons and ligaments for tensile strength (Alevelnotes.com, 2016).
The first stage of cellular respiration is glycolysis. It occurs in the cytosol of the cytoplasm. Enzymes split a molecule of glucose into two molecules of pyruvate also known as pyruvic acid. This process is believed to have evolved before oxygen because it is an anaerobic process.
The Krebs cycle itself actually begins when acetyl-CoA combines with a four-carbon molecule called oxaloacetate. This produces citric acid, which has six carbon atoms. This is why the Krebs cycle is also called the citric acid cycle. After citric acid forms, it goes through a series of reactions that release energy. The energy is seized in molecules of NADH, ATP, and FADH2, another high energy compound.
Electron transport is the last phase of aerobic respiration and it occurs in the mitochondria. In this stage, energy from NADH and FADH2, which result from the Krebs cycle, is transferred to ATP. ATP synthase acts as a channel protein, helping the hydrogen ions across the membrane. It also acts as an enzyme, forming ATP from ADP and inorganic phosphate (CK-12 Foundation, 2017).
A Slight change in protein expression in the haemoglobin lead to potential death from sickle cell anaemia and the over-consumption of carbohydrate and lipids can lead to obesity, diabetes and numerous health complication. Although research has shown that sugar is the main culprit, not lipids. An element which is essential for all this process to occur in living cells is Carbon, because of its versatile binding capability. Since without it the formation of DNA, RNA, protein, lipids and carbohydrate will not be possible.
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Varaitch S, (2017) Class note: Protein
Appendix 1: Codon table
Appendix 2: Images of both the disc shaped and sickle cell shaped Erythrocyte
Appendix 3: DNA and RNA nucleotide ann the double Helix showing complimentary base pairing
Appendix 4: DNA Transcription, Translation to protein
Appendix 5: DNA transformation to Chromosome
Appendix 6: Recombinant phase of meosis 1
Appendix 7: Punnet Square
Appendix 8: Cell membrane
Appendix 9: Lock and key theory