Cell Structure and Function Flashcards
Transcription: Initiation
TBP binds to TATA box found at the start of promoter sequence.
Transcription factors bind to promoter.
RNA polymerase II binds to promoter and begins transcription
Transcription: Elongation and Termination
Transcribes from 3’ to 5’ on the template strand to give a mRNA strand from 5’ to 3’.
10 bases exposed at any given time.
Transcription ends at the polyadenylation signal (AAUAAA). Enzymes detach RNA polymerase and mRNA.
Transcription: Processing
Guanine cap added to 5’ end.
‘Tail’ of 50-250 adenines added to the 3’ end.
Introns edited out by spliceosomes, which look for donor and acceptor sequences at the start and end of an intron.
Translation: Initiation
mRNA binds to small subunit of ribosome that already has tRNA with methionine bound. Subunit scans mRNA for AUG codon for tRNA to bind to. Large subunit binds using energy from a GTP.
Translation: Elongation
tRNA with complementary anticodon to the next codon binds to aminoacyl site. Enzymes catalyse peptide bond between new amino acid and peptide chain.
Original tRNA moves into E site to be ejected and new tRNA moves into p-site.
Ejected tRNAs reloaded with necessary amino acid by aminoacyl-tRNA-synthetase.
Translation: Termination
Release factor binds to a stop codon to stimulate hydrolysis of bond between tRNA and last amino acid. 2GTPs are hydrolysed to separate the two ribosome subunits.
Function of the SRP
SRPs recognise sequences of amino acids near the N-terminus called signal polypeptides and pause transcription. Ribosomes stimulated to move to RER, where the SRP detaches and translation recommences, releasing the polypeptide into the RER.
Polypeptide chain modified by chaperone proteins in RER for secretion.
Protein Synthesis Errors: Transcription
Absence of RNA Polymerase II: no transcription.
Spliceosomes non-functional: Introns not removed and also translated. Incorrect primary structure.
mRNA not proofread: Incorrect codons leading to incorrect primary structure.
Protein Synthesis Errors: Translation
Correct translation factor absent: Translation cannot begin
Signal Polypeptide not recognised by SRP: No translocation to RER, so no chaperone protein to fold the polypeptide-incorrect tertiary structures.
Protein Synthesis Errors: Sorting
Incorrect molecular tags on vesicles or proteins: Protein/vesicle delivered to wrong target structure.
Similarly, the SRP error can prevent secretory proteins from being secreted because they are not placed into vesicles.
Protein Synthesis Errors: Modification
Failure to/over phosphorylating: Protein is inactive/too active.
Cell Signalling: Reception
Ligand binds to cell surface protein receptor which undergoes conformational change.
Conformational change causes receptor to bind to G-protein and a GTP displaces the GDP currently on the G-protein.
Activated G-protein detaches and diffuses across the membrane until it reaches and binds to an integral protein enzyme, which also undergoes a conformational change and activates it to begin transduction.
GTP bound to G-protein is hydrolysed back to GDP and Pi and the G-protein dissociates from the enzyme.
Cell Signaling: Transduction (+ cAMP Example)
Membrane bound enzyme activated by G-protein begins to synthesise secondary messengers. eg: adenylyl cyclase which synthesises the secondary messenger cyclic AMP from ATP.
cAMP phosphorylates protein kinase A and activates it, which will go on to phosphorylate more protein kinases. Afterwards, protein phosphotase will dephosphorylate the kinases to deactivate them.
cAMP is degraded by phosphodiesterase to prevent constant stimulation of kinases.
Cell Signalling: Transduction (+Ca2+ example)
Phospholipase C is the integral membrane enzyme and hydrolyses PIP2 to IP3 and DAG. IP3 is the first secondary messenger and binds to Ca2+ channels on the RER to trigger Ca2+ release. Ca2+ is the second secondary messenger.
Reason for the Cascade
Every kinase-activation acts as a control for the activity of the protein. If a kinase at a level is over-activated, the dephosphrylating mechanism in the next level will reduce the effect by inactivating all the excess kinases.
Interphase
G1: Metabolically active state. Replication of organelles for daughter cells and centrosomes for mitosis. Nondividing cells are in G0.
S: DNA replication occurs by semi-conservative replication.
G2: Enzymes and proteins required for mitosis is synthesised. Centrosome production completed.
Prophase
Early prophase: Condensation of chromatin into sister chromosomes. Joined at the centromere by cohesins. Centrosomes move to the poles of the cell and tubulin microtubules form.
Late prophase: Nuclear membrane disintegrates. Microtubules will attach to kinetochores at the centromeres and move the chromosomes back and forth to reach an equilibrium position.
Shorter microtubules form an aster around centrosomes to anchor them to the membrane.
Metaphase
Chromosomes reach the metaphase plate.
Anaphase
Cohesins are cleaved by enzymes. Kinetochore tubules shorten and pull chromosomes towards the poles.
Non-kinetochore microtubules push off each other to lengthen cell.
Telophase
Nuclear membrane reforms. Chromosomes dissociate back to chromatin. Microtubules degrade back to tubulin
Cytokinesis
Microtubules form a furrow that eventually cleaves the cell.
G1 Checkpoint
At the end of G1 phase. Checks for DNA integrity and whether the cell is prepared to undergo mitosis. If not, then the cell enters G0.
G2 Checkpoint
Occurs just before mitosis. Controlled by cyclin, which is accumulated during interphase, where it is protected by degradation. Cdk binds to cyclin at the checkpoint and forms MPF , which is an enzyme required to activate enzymes in mitosis. Cyclin is degraded in this process and MPF breaks down by the end of mitosis and Cdk recycled.
M checkpoint
Checks if all chromosomes are attached to microtubules before anaphase occurs to prevent non-disjunction.
Tumour Suppressor Gene Mutation
Mutation leads to the production of a protein with the wrong structure, which is non-functional.
Examples: TP53, APC, BRCA1/2
Proto-oncogenes Mutation
Actual mutation: Production of hyperactive form-overstimulates cell growth.
Extra copies: More protein produced due to more mRNA transcribed.
Wrong promoter: gene expression not controlled by the correct stimulus, can lead to continued expression.
Symptoms of Diabetes Mellitus (10)
- Excessive thirst (polydipsia)
- Frequent urination (polyuria)
- Extreme hunger or constant eating (polyphagia)
- Unexplained weight loss
- Presence of glucose in the urine (glycosuria)
- Tiredness or fatigue
- Changes in vision
- Numbness or tingling in the extremities (hands, feet)
- Slow‐healing wounds or sores
- Abnormally high frequency of infection
Products of each step of Aerobic Respiration per glucose
Glycolysis: 2 ATP, 2 NADH
Link Reaction: 2 NADH, 2 CO2
Krebs’ Cycle: 2ATP, 6 NADH, 2 FADH2
Electron Transport Chain: 26-28 ATP `
Process of Glycogenesis
Glucose phosphorylated by hexinase to glucose-6-phosphate, Glucose-6-phosphate isomerised to glucose-1-phosphate, then uridine disphosphate before being joined to a glycogen.
Process of Glycogenolysis
Glycogen converted to glucose-1-phosphate by phosphorylase, then glucose-6-phosphate and at last glucose by phosphatase. Skeletal muscles only convert to glucose-1-phosphate as they do not have phosphatase. Only hepatocytes convert glycogen to glucose.
Uses of Krebs Cycle intermediates
Citrate: Synthesis of Fatty Acids
Alpha-ketoglutarate: Synthesis of Amino Acids
Malate: Gluconeogenesis
Oxaloacetate: Amino acid synthesis
