Biology 1A03 Notes (1) PDF

Biology 1A03, September 30th, 2024, Theme 1: Module 1: The Composition and Structure of Membranes ▫ Estimated 10 trillion cells in an adult human ▫ Eukaryotic cells: Plant cells, animal cells, fungi ▫ Prokaryotic cells (no true nucleus): bacteria cells ▫ 10x as many bacteria cells th...

Biology 1A03, September 30th, 2024, Theme 1: Module 1: The Composition and Structure of Membranes ▫ Estimated 10 trillion cells in an adult human ▫ Eukaryotic cells: Plant cells, animal cells, fungi ▫ Prokaryotic cells (no true nucleus): bacteria cells ▫ 10x as many bacteria cells than our own cells, make up 2-3% of our body weight ▫ Microbiome: a population of microorganisms (organisms that aren’t visible to the naked eye) or microbes ▫ Cell: membrane bound structure containing macromolecules 1. Nucleic acids (DNA & RNA), 2. Proteins, 3. Polysaccharides, 4. Phospholipids (primary component to cell membrane) ▫ Membranes separate an internal environment from the external environment. This allows these distinct environments to have different chemical compositions ▫ Cell membrane is made up of lipid macromolecules, each have hydrophobic and hydrophilic properties that allow “stacked” lipid bilayers to form. ▫ Cell membranes are very thin from 5-10 nm ▫ Phospholipids are the main component of the membrane → Typically, 16-18 carbons in a single chain. → The bonds connecting the carbons may be single bonds (saturated) or double bonds (unsaturated). → These properties change the shape, size, and behaviour of the phospholipids and ultimately the membrane ▫ Amphipathic, since they have both hydrophobic and hydrophilic components ▫ Another important component of the cell membrane is steroid, ig. Colesterol → Characterized by a 4-hydrocarbon ring structure ▫ Water molecules interact with the head of the regions, but not the tails of the phospholipids ▫ These lipid aggregates (micelles, becomes a bowl shape) form spontaneously, without the use of any energy ▫ Phospholipids can move laterally within the cell membrane lipid bilayer (L, R, F, B) → However, phospholipids cannot easy flip from one layer to the other in the bilayer without the use of a great deal of energy ▫ The fluidity of membranes can be affected by many factors, → 1. Number of carbons in the fatty acid tails: # of carbons vary, typically between 16-18, longer chains pack together more tightly affecting fluidity 2. Unsaturated or saturated fatty acids: double bonds produce kinks / bends in the chain which pushes neighbouring phospholipids further apart increasing fluidity 3. Temperature: higher temps. Increase fluidity, colder temps. Decrease fluidity, cold adapted organisms tend to have unsaturated phospholipids to maintain fluidity 4. Cholesterol: can be found in all membranes, can strain fluidity by packing closely to phospholipids, lower temps make the bilayer behave like other fats by solidifying, however cholesterol maintains fluidity by keeping them apart ▫ Regions of low fluidity have lipid rafts, which can hold macromolecules together, they gather proteins found in the same metabolic pathways or a collection of receptors on the surface of the cell → lipid rafts are taller because of the longer saturated lipids which pack together tighter and can hold the macromolecules in the raft ▫ Macromolecules can move laterally through the cell membrane, the fluidity allows transmembrane movement (internal to external and v.v), → Lower permeability: less fluid membrane with fewer unsaturated fatty acids and more cholesterol → Higher permeability: more fluid membrane with more unsaturated fatty acids and cholesterol ▫ The ability of cell membranes to control the traffic of substances into and out of the cell and its organelles makes them selectively permeable → Small molecules and ions can cross the membrane through a concentration gradient that is from areas of high to low concentration with diffusion → Small and non-polar molecules can pass relatively quickly → Charged, polar, and large molecules have difficulty passing, if they do at all → Cell membranes are NOT exclusively made up of lipid macromolecules, they are a mosaic of lipids, proteins, and carbohydrates → Proteins embedded in the bilayer can facilitate transport across a membrane which allow efficient transport of molecules, ig. Bigger molecules ▫ The Fluid Mosaic Model: membranes consist of proteins and carbs embedded in the fluid bilayer (models make predications of natural phenomena) ▫ Passive diffusion: from areas of high to low concentration (along a gradient) ▫ Passive transport (facilitated diffusion): from areas of high to low concentration (along a gradient).  1. Simple diffusion: a solute molecule comes in contact with and cross and the lipid portion of the plasma membrane into the cell. Movement along a concentration gradient (no energy required) 2. Facilitated diffusion requires protein molecules that assist in the transmembrane movement of solutes (no energy required) 3. Aquaporins: are exclusively permeable to water, these protein channels allow water to move across the cell membrane through osmosis, the movement is concentration gradient dependent Hypertonic: more concentration, water will flow into Hypotonic: less concentration, water will flow out of ▫ Active transport: molecules move against the concentration gradient (fueled by energy from the hydrolysis of ATP) 1. Primary transport: direct expenditure of ATP-dependent (sodium-potassium pump: cell establishes concentration differences in sodium and potassium on either side of the cell membrane. There is a higher concentration of K extracellularly than intercellularly, and there is a higher K in our cells than out in our body. This difference is maintained by the active role of the pump → For every 3 Na ions that are pumped out of the cell, 2 K ions are pumped into the cell. 2. Secondary transport: indirect expenditure. Biology 1A03, September 30th, 2024, Theme 1: Module 2: Organelles and Energy Acquisition ▫ Life and photosynthesis began ~4 million years ago ▫ Eukaryotic cells: an organism whose cells contain a nucleus, and many membranes bound organelles ▫ Prokaryotic cells: unicellular organisms that lack a nucleus and have few to no organelles ▫ Organelles: membrane-bound structure inside the cell → Chloroplasts, in plant cells → Mitochondria, in animals and plant cells (converts the energy from the food we eat into energy that powers cellular functions) ▫ Photosynthesis: a process in plant cells and other organisms that convert light energy into chemical energy. Chemical energy is stored into the bonds of carbohydrate molecules → Chloroplasts have double membranes around its exterior, and an interior that is filled with hundreds of stacked membranes called Thylakoids. → Thylakoids: organized into piles called grana (granum), pigments and enzymes participate in photosynthesis  ▫ Cellular respiration: a process used by plant and animal cells to release the chemical energy stored in the bonds of carbohydrate molecules and partially capture it in the form of ATP → Each membrane has two membranes: Outer membrane (surrounds the organelle), and inner membrane (connected to a series of sac-like structures called cristae) in these membranes is where most of the ATP is synthesized ▫ The Endosymbiotic Theory: states that these temporary relationships are permanent and heritable. Consistent with this theory, the same proteins and genes should be found in bacteria, chloroplasts, and mitochondria. ▫ Photosynthesis: the process of using sunlight to produce carbohydrates ▫ Carbohydrates: are made up from monosaccharides that polymerize via glycosidic linkages to form disaccharides ▫ Glucose processing produces most of the electron carriers that are used to make ATP Biology 1A03, September 30th, 2024, Theme 1: Module 3: Structure of the cell ▫ Proteins have various functions: 1. Transport and signalling 2. Movement and structure 3. Enzymes 4. Defense ▫ Proteins can have different sizes and shapes which affect their overall functions ▫ The gene for each protein synthesis is found in the DNA → Step 1: transcribe information into RNA ▫ In eukaryotes, the nucleus is a double membrane-bound organelle that contains chromosomes which pack and control DNA molecules → Nucleus contains a region called Nucleolus and it is within this that the ribosomal molecules are transcribed → Before protein synthesis can occur, the appropriate segment is read and transcribed into RNA → The double-membrane of the nuclear envelope has imbedded nuclear core complexes that allow materials to flow in and out → Most ribosomal membranes are manufactured in the nucleolus where they bind to proteins and form ribosomal subunits these are then exported to the cytoplasm ▫ Ribosomes: cellular machinery involved in the synthesis of proteins → The structural components are made in nucleolus and then are shipped out of the nucleus. Once exported, they assemble and have large and small subunit components that contain RNA molecules and proteins → Ribosomes can remain soluble in the cytosol as “free” or bind to the RER to become bind ribosomes; they produce different proteins that are destined for different part of the cell ▫ All cells produce many distinct proteins → All possible proteins are derived from 20 core Amino Acids; central carbon bound to an amino group, carboxyl group, H atom, and variable side chains represented by R → Amino Acid monomers are put together to create linear strands called polymers and polypeptides → Polypeptide: strand of amino acids that are covalently bound to one another by a condensation reaction which releases water. This bond can be broken by hydrolysis (breaking by addition of water) ▫ During protein synthesis, the unique sequence of amino acids in each protein is referred to as the primary structure of that protein ▫ The condensation reactions that join amino acids are catalyzed in the ribosome ▫ During translation by ribosome, amino acids polymerize to form primary structures when a bond form between a carboxyl group of one amino acid and the amino group of another ▫ The C-N bond that comes from the condensation reaction is called a peptide bond. When amino acids are linked together in this manner, they are referred to as residue and the formed polymer is called a polypeptide ▫ The AA side chains differ in size, shape, and chemical properties, some are hydrophobic and some hydrophilic. ▫ Free ribosomes translate proteins that will remain in the cytosol or be targeted to organelles that include the nucleus, mitochondria, and chloroplasts. Other proteins can be transported through the nucleus pores into the nucleus which can act as histone proteins or transcription factors ▫ The side chains of the AA residues, whether they are hydrophilic or hydrophobic determine the overall shape of the protein ▫ All proteins take on a 3D fold → Primary structure: sequence of information, largely decides the manner of the fold → Secondary structure: interaction between the proteins backbone that are responsible for the following formations. 1. Alpha Helix: The AA and carboxyl groups are attached by covalent bonds called peptide bonds to form the polypeptide chain. In addition, the polymer is turned into a spiral / coil by the formation of a non-covalent bonds called H-bonds. H-bonds form between the carbonyl of the carboxyl group of one AA residue, and the amide of the other amino group of AA 4 positions away making consequently making the R groups stick out of the helix 2. Beta Sheets: made up of parallel protein strands with H-bonds also formed between the carboxyl and amino groups between the adjacent strands. H-bonds allow for pleated like organization → Tertiary structure: With regards to the overall shape, it’s all due to the interactions between the variable side chain that allows the protein back bone to bend and fold which lead to the 3D shape. Various interactions that can occur; H-bond,VDW, covalent and ionic bonds, disulfide bonds, hydrophobic interactions → Quaternary structure: There are cellular mechanisms that assist protein folding. 1. Molecular chaperons: These proteins bind to hydrophobic regions of the polypeptide and prevent the wrong folding just long enough for the structure to form. 2. Chaperonins: They are large molecule complexes that form isolation chambers. Inside is a single protein that is isolated away from others that they can fold without interference → Endomembrane system: includes the nuclear envelop, ER, Golgi apparatus, and lysosome, and allows for the compartmentalization of the cell for different roles ▫ mRNA that encodes proteins that are destined for the endomembrane system include a special signal sequence that once translated, causes the ribosomes to become bound to the ER. → Once this signal sequence appears, it binds a signal recognition particle (SRP) which then binds to a signal recognition particle receptor (SRPR) in the ER membrane → Once this interaction occurs, the polypeptide can continue to be translated and is able to enter the lumen (central canal) of the ER → Inside the lumen, the signal sequence is removed, and the translated polypeptide is now able to undergo important changes that allow for the final stages of protein processing and maturation to occur ▫ While some proteins remain in the ER, many proteins will continue to journey to their destination within vesicles: small membrane-bound compartments in the cell that bud off from the ER. → The ER is also the site where proteins get modified by the addition of one or more carbohydrate chains (glycosylation) → Glycosylation: occurs on most secreted membrane bound proteins and can contribute to protein stability, folding, and even cell-cell recognition. ▫ Once released from the ER, the next destination is the Golgi apparatus. Some of the glycosylation reactions can occur in the Golgi apparatus. Proteins are transported out the Golgi apparatus in vesicles that pinch off from the ER. These vesicles are then able to fuse with the Golgi and deposit their contents in the lumen of the Golgi apparatus → In the Golgi apparatus, further protein modifications can include the addition of carbohydrate groups.  → Some proteins will go to the cell membrane, others will be secreted out of the cell, or perhaps to other organelles. → There is evidence to suggest that each protein that comes out the Golgi apparatus has a tag that allows for it to be packaged into a particular type of transport vehicle. These transport vesicles also have their own respective tags that allow for them to be transported to the appropriate destination- the cell membrane, lysosome, or even back to the ER. → Once these vesicles reach their destination, the vesicle phospholipid bilayer fuse with that of the cell membrane ▫ Cytoskeleton: dense network of fibers that helps maintain and change cell shape. → One of these cytoskeletal components are the microtubules → These structures are protein polymers that form long fibers which stretch through the cell. They function as cellular roadways that allow for vesicles to be transported along. ▫ Proteins destined for the mitochondria, chloroplast, and peroxisomes are synthesized on free ribosomes. In some cases, the proteins fold before transport to the organelle, in others, folding occurs after → Some proteins are targeted to the lumen of the organelle while other proteins are embedded in the membranes of the organelle ▫ Each aquaporin is made up of 4 protein subunits that together form the tetrameric aquaporin channel (quaternary structure) → Each subunit contains membrane-spanning alpha-helices that form a central pore. As result, each monomer forms a functionally independent water pore and allows water to move through in either direction. Biology 1A03, September 30th, 2024, Theme 1: Module 4: Nucleic Acids ▫ In prokaryotic cells, the majority of DNA is contained in the nucleoid. → There are also small circular DNA molecules called plasmids. These plasmids often carry one or two genes. This allows for the rapid spread of genes that confer properties. ▫ Chromosomes: the organization of a double-stranded DNA molecule in its association with proteins and RNAs. → Organelles such as the mitochondria contain their own smaller chromosomes ▫ Supercoiling: occurs in a circular molecule, it is the coiling that occurs in the addition to the coil of the helical DNA structure. It preserves the double helix structure and compacts the DNA into a smaller space  ▫ Transformation: a change in cell behaviour resulting from the incorporation of hereditary material from outside the cell (Griffith’s experiment) ▫ The basic subunits of the DNA molecule are the nucleotides → Nucleotide: can be described by its three constituent components: a phosphate group, 5- carbon deoxyribose sugar, and a nitrogenous base → The four nucleotides that constitute DNA are chemically distinguished by the specific nitrogenous base found in the molecule ▫ Pyrimidines (single ring): Cytosine, Thymine ▫ Purines (two rings): Guanine, Adenine ▫ There are 2 H-bonds between A-T and 1 H-bond between G-C ▫ Helix has a major groove and a minor groove, with a turn occurring at every 10 nucleotides ▫ All RNAs are synthesized the same way, as a transcription of a sequence of DNA using an enzyme called RNA polymerase ▫ RNA can be categorized: mRNA, rRNA, tRNA, and difference enzymes synthesize different RNA’s ▫ To code information in the DNA, we must have all classes of RNA molecules ▫ mRNA: a single-stranded RNA molecule that is a copy of a gene that codes for a protein ▫ tRNA: carries AA into the ribosome and matches the AA to the appropriate mRNA sequence (never translated) ▫ rRNA: multiple rRNAs and proteins form the functional ribosome complexes that perform translation of mRNA into proteins ▫ The DNA molecules in eukaryotic cells are linear molecules that are organized around proteins called histones that make up a chromatin Biology 1A03, October 1st, 2024, Theme 2: Module 1: Transcription ▫ DNA molecules are often described as the “blueprint,” as they will each contain thousands of proteins or RNA molecules ▫ Genes are sections of the DNA which contain information that is then transcribed into an RNA copy ▫ Central Dogma: The process of copying and interpreting genes into proteins. It proposes that the info in the DNA acts like a blueprint and will specify the sequences of bases in an RNA molecule, which then specifies the sequence of AA in a protein → DNA can be copied multiple times into mRNAs which can then be translated into the nucleotide language and then into the AA language of the protein. → This whole process from DNA to mRNA to protein is the process of Gene expression ▫ The genetic information that codes for the RNA is contained on the genes of a chromosomes ▫ RNA molecules can be found to contain a single strand ▫ During transcription, DNA is utilized as a template to generate a complimentary and anti- parallel molecule, → only one DNA strand in each gene will be transcribed → As transcription occurs, the nucleotide sequence that is contained within the gene is what will determine the sequence of nucleotides contained within the RNA transcript → Because the RNA is transcribed of the compliment of the strand, the sequence of the RNA is the same as the non-template strands except for that Uracil replaces thymine ▫ For RNA to be transcribed from DNA, an enzyme called RNA polymerase attaches to specific promoter regions of the DNA ▫ Promoter regions: indicate the transcriptional starting point where the transcription begins and are situated upstream or 5’ in the gene of interest ▫ 5’ end: named for the 5’ phosphate on the nucleotide ▫ 3’ end: named for the 3’ hydroxyl group on the nucleotide ▫ DNA is read in the 5’ to 3’ direction ▫ RNA polymerase will recognize and bind to a promoter and once transcription is initiated it will move alone the 3’ to 5’ direction until the terminating sequence is in place ▫ Transcription occurs within the RNA polymerase enzyme → once RNA polymerase binds to the specific promoter regions of the DNA is it able to open the double stranded DNA revealing the template and non-template strand within a transcription bubble. → The RNA polymerase can then begin to catalyze the production of an anti-parallel RNA strand that is complimentary to the template creating an RNA-DNA duplex ▫ As transcription continues, the RNA polymerase continues to move downstream from the promoter site while unwinding the DNA helix and creating the RNA polynucleotide transcript → As the RNA molecule is synthesized, it dissociates with the DNA template and the DNA helix can reform ▫ A single gene can be transcribed by several RNA polymerase molecules at a time ▫ Because the DNA molecules in a cell contains many genes, when any one gene is being transcribed, it is important to terminate the process when the end of the sequence is reached → This is facilitated through termination sequences in the DNA located in the 3’ end → Enable the release of the RNA transcript ▫ Prokaryotes have two types of terminating sequences; → Rho independent terminated sequence: inverted nucleotide sequences, series of nucleotides that are followed downstream by a specific reverse compliment. They are  transcribed and then folded back onto themselves to form a G-C rich hair-pin loop along the same mRNA strand. Pauses the RNA polymerase and leads to the release. → Rho dependent terminated sequence: uses a specific prokaryotic protein (Rho factor) which can bind to and use ATP energy to move along the formed RNAtranscript while unwinding it from the template. They can destabilize the interaction between RNA and DNA template ▫ Prokaryotes have no nuclear envelope that separates the process of transcription and translation ▫ While the RNA polymerase in bacteria requires only a sigma factor to directly recognize and bind the promoter region, in eukaryotes, several specific proteins called general transcription factors are required to mediate the binding of RNA polymerase to a promoter and to initiate transcription ▫ Eukaryotes require the presence of three different types of RNA polmyerase: RNA polymerase 1, 2, and 3 → RNA polymerases 1,3: transcribe structural, non-coding RNAs. RNA polymerase 1 transcribe the genes for the rRNA, the RNA polymerase 3 transcribes the genes for the tRNA, as well as other small regulatory RNA molecules. → RNA polymerase 2: that transcribes the messenger RNAs, which serve as the templates for production of protein molecules ▫ Post-transcriptional modification: occur at each end of the primary mRNA transcript → They include the addition of a 5’ cap, and a 3’ poly tail. Both 5’ and 3’ modifications are important to ensure the stability of the mRNA molecule. These modifications can ensure the export of the mRNA from the nucleus, help protect against the ribonuclease, enzymes that target phosphodiester bonds, and help with attachment of the ribosome and initiation of transition once the mRNA reaches the cytoplasm of the cell. ▫ All transcribed mRNA molecules have a number of adenine nucleotides added to the 3’ end, this is referred to as the poly (A) tail ▫ Polyadenylation: when the poly (A) enzyme is able to add between 150-200 adenine nucleotide bases to the 3’ end ▫ Exons: The sequences of the mRNA that are necessary for coding the sequence of AA in the protein ▫ Introns: The intervening sequence → In transcribing a gene from DNA to RNA, an RNA polymerase will transcribe both the introns and the exons from the DNA, but the introns need to be removed from the mRNA and the exons need to be joined or spliced together prior to translation through a process called RNA splicing (if this does not occur, the protein may contain the wrong sequence of AA)  → RNA Splicing: occurs at specific short nucleotide sequences that are situated at each end of an intron. → The process of RNA splicing is catalyzed by large molecule machines called spliceosomes ▫ Transcription of DNA into mRNA is then followed by the export of this mRNA from the nuclear compartment to the cytoplasm of the cell → Facilitated by nuclear pore complexes in the nuclear membrane that act as gateways for molecules to move into and out of the nuclear. The nuclear pores are protein-lines channels that pass through both membranes of the nuclear envelope. They can also transport proteins, carbohydrates, and important signaling molecules into the nucleus Biology 1A03, September 30th, 2024, Theme 1: Module 2: The genetic code ▫ It is important to note that codons are always written in the 5’ to 3’ direction ▫ Only the nucleotide triplet AUG codes for methionine. This unique triplet is the first triplet in every protein coding sequence. It is the AUG start codon that signals the region where protein synthesis should begin ▫ Transcription: reading genetic information from a DNA template and synthesizing a complementary RNA molecule ▫ The coding region of a gene is the open reading frame, they reflect the way in which a nucleotide sequence is read