H2 Biology: Book 3 Questions

Outline cell signalling pathway.

Signal Reception

1. Detection of signal occurs when the extracellular signal molecule binds to a specific receptor protein located on the cell’s surface

2. Large, hydrophilic molecules are unable to diffuse across the hydrophobic core of the cell membrane, has signal molecules act as ligands to bind to specific complementary sites on the cell surface receptor to form a ligand-receptor complex

3. Receptor protein then undergoes a conformational change/subunit aggregation, directly activating the receptor protein, enabling it to intract with other molecules in the cell.

Signal Transduction

1. Activated cell surface receptors initate 1 or more signal transduction pathways

2. Transduction occurs via a multistep signal transduction pathway which consists of a series of relay proteins, usually enzymes in a specific sequence

3. Each relay protein in the pathway catalyses the conformational change, and hence activates/inhibits, of the protein immediately downstream

4. Protein kinases phosphorylates, and hence activates other protein kinases, turning on STP

5. Phosphatases dephosphorylate, and hence inhibits protien kinases, turning off STP when the initial signal is no longer present, allowing protein kinases to be reused

6. This forms a phosphorylation cascades that transmits the signal received at the cell surface into the cytosol

Cellular Response

1. The signal transduction pathway eventually leads to the regulation of 1 or more cellular activites

Define signal reception.

Signal reception is the target cells’s detection of a extracellular signal molecule.

Define cell signalling

Cell signalling is the process by which cells communicate with one another, ensuring cellular activities occur in the right cells, at the right time, and in proper coordination with other cells, through detecting and sending signals.

Define signal transduction.

Signal transduction is the process by which as cell converts an extracellular signal into an intracellular signal, resulting in a specific cellular response.

Define signal amplification.

Signal amplification is the process of enhancing signal strength as a signal is relayed through the signal transduction pathway.

Describe how the structure of G-protein linked receptors are adapted to its function.

1. Each G protein is made of 1 polypeptide chain

2. Each G protein has 7 a-helices which contain hydrophobic amino acids, causing hydrophobic interactions to exist between the a-helices, and between them and the hydrophobic fatty acids of the phospholipid bilayer, allowing the membrane-embedded domain to remain stabilized and embedded in the phospholipid bilayer

3. Hydrogen bonds and disulfide linkages are formed between non-helical segments, stabilizing the protein

4. The N-terminus and 3 non-helical segments form the extracellular domain, containing specific amino acids that form the extracellular signal binding site, and the C-terminus and 3 non-helical segments form the intracellular domain, containing specific amino acids at the G-protein interaction site —> enables the signal-binding site/G-protein interaction site to have specific 3D conformation to allow binding to specific ligands/interaction with G proteins

5. Hydrophilic amino acid residues form N & C termini, inter-helical loops, to allow the intracellular & extracellular domain to be soluble in aqueous matrix, and allow binding of water-soluble ligands/G protein

6. Binding of ligand to GPLR causes conformational change in protein, allowing it to interact with G protein, hence allowing GPLR to initiate signal transduction pathways via activation of G-protein.

Explain how insulin helps to regulate blood glucose concentration, including its cell signalling pathway.

1. The increase in blood glucose concentration above set point of 90mg/100ml is detected by the islets of Langerhans in pancreas.

2. Ligand binds to cell-surface receptor tyrosine kinase, resulting in protein dimerisation and aggregation, leading to activation of its tyrosine kinase activity, resulting in auto-phosphorylation

3. Each RTK domain adds 1 phosphate from an ATP molecule to tyrosine on the tail of its own polypeptide subunit

4. Activated RTK then binds cytoplasmic relay proteins, altering their activity

5. Relay proteins specific to the insulin receptor bind to specific phosphorylated tyrosine on receptor and is activated, each of which activates a signal transduction pathway.

Cellular Response

1. Stimulate migration and fusion of vesicles containing GLUT4, a extra glucose transporter, to the plasma membrane, increasing the conc. of GLUT4 in the plasma membrane

   1. Increases uptake of glucose into all insulin-dependent cells

2. Increase rate of glycolysis (conversion of glcuose into pryuvate / lactate) for production of ATP in all insulin-dependent cells

3. Stimulate glycogenesis: activated insulin receptors activvate glucokinase, which phosphorylates glucose into glucose-6-phosphate, which is used in the synthesis of glycogen

4. Inhibits glycogenolysis

5. Stimulates amino acid absorption & protein synthesis

6. Inhibits gluconeogenesis

7. Stimulate lipogenesis in adipose tissues, increasing absorption of glucose into adipocytes where it is converted into triglycerides

This causes a decrease in blood glucose concentration back to the set point of 90mg/100ml. Negative feedback mechanisms prevent further release of insulin, as the decrease in conc. acts as a negative feedback signal for decreased stimulation of B cells, so lesser insulin is released, no further decrease in blood glucose concentration.

Explain how glucagon regulates blood glucose concentration, making reference to its cell signalling pathway.

The decrease in blood glucose conc. is detected by the islets of Langerhans in the pancreas, which stimulates a cells to secrete more glucagon, inhibiting the secretion of insulin by B cells.

1. Ligand binds to extracellular signal-binding site of GPLR, resulting in conformational change in the receptor, leading to increased affinity for the G protein

2. Intracellular domain of GPLR binds to inactive G-protein, causing GTP to displace bound GDP, activating the G protein

3. The activated G protein disassociates from the GPLR, diffusing along the membrane and binds to adenylyl cyclase, catalysing the synthesis of many cAMP molecules from ATP

4. cAMP activates protein kinase A, which phosphorylates other proteins, serving as 2nd messengers

Cellular Response

1. Inhibit glycogenesis

2. Stimulates glycogenolysis: breakdown of glycogen into glucose

3. Stimulates gluconeogenesis synthesis of glucose from non-carbohydrate precursors

4. Stimulates lipolysis: breakdown of triglycerides to release fatty acids to be used as energy source, only under prolonged hypoglycemia

This results in increased blood glucose conc. back to set point of 90mg/100ml. Negative feedback mechanisms occur to prevent further release of glucagon, with the increase in blood glucose concentration acting as negative feedback signal for decreased stimulation of a cells, hence lesser glucagon released, no further increase in blood glucose conc.

What are the benefits of cell signalling being a multi-step process?

1. Signal amplification: At each catalytic step of the cascade, the no. of activated products is much greater than the preceding step, and with the presence of multiple steps, a small number of extracellular signal molecules is sufficient to elicit a large cellular response.

   1. Persistence of proteins in pathway in active form long enough to process numerous molecules of substrate before inactivity

2. Provide more opportunity for regulation and coordination

   1. For a cell to remain sensitive, and continually repsond to incoming signal, each molecular change in its signalling pathway must only last a short time, so reversibility of changes elicited must be possible

   2. Entails signal termination: signal response is terminated by processes which return receptor and each component of signal transduction pathway to inactive states

   3. Reception and transduction stages serve as regulation points, with mechanisms of

      1. Phosphatase activity: catalyse dephosphorylation/inactivation of kinases —> impede transduction pathway downstream

      2. Intrinsic GTPase activity which catalyses rapid hydrolysis of GTP into GDP, inactiving G-protein

      3. Phosphodiesterase activity: catalyses cAMP —> AMP, reducing conc. of cAMP

3. Specificity of cell signalling: the specific combination of signalling proteins (receptors, relay proteins) results in great specificity in the signal it detects and the response it elicits, hence 2 cells respond differently to same signal by differing in 1 or more proteins that receive/transduce/respond to the same signal

Explain how specificity of the response is determined in different cells.

1. Different cells express different receptors that bind to particular ligands

2. Different cells have different relay proteins that activate different downstream molecules, leading to different responses in different cells from the same signal molecule

State the similarities between insulin and glucagon receptors.

1. Both are glycoproteins that span the cell surface membrane

2. Both are globular proteins with specific 3D conformations

3. Binding of specific ligand causes receptors to undergo conformational change

4. Both have extracellular binding site with specific 3D conformation complementary to that of a specific ligand

5. Both have intracellular binding site with a specific 3D conformation complementary to that of a specific relay protein

6. Both are involved in the regulation of blood glucose concentration about the set point of 90mg/100ml

Describe the mitoic cell cycle.

Interphase comprises of 90% of the cell cycle, and consists of:

1. G1 phase: cell increases in size and acquires ATP, and undergoes intensive cellular gene expression to synthesis appropriate organelles & proteins

2. S phase: Each DNA molecule undergoes semi-conservative DNA replication where each parental DNA molecule is used as a template to synthesise a complementary daughter strand, giving rise to genetically identical DNA molecules, ensuring the integrity of genetic information in daughter cells. Histone proteins are synthesised and associate with the DNA molecule, and they remain fully uncoiled and decondensed as chromatin.

3. G2 phase: cells increase in size and acquires ATP, further synthesis of appropriate organelles and proteins with centrioles replicating and the mitoic spindlestarts to form

Mitosis:

1. Prophase:

   1. Nuclear envelope disintegrates into small vesicles, nucleolus disappears

   2. Chromatin becomes more tightly coiled, condenses into discrete chromosomes

   3. Centrioles migrate to opposite poles of the cell, spindle fibre continues to develop

2. Metaphase:

   1. Centriole pairs are positioned at opposite poles of each cell, with shortening & thickening of chromosomes at its maximum

   2. 2 sister chromatids are joined together at the centromere, with a kinetochore attached to the centromere

   3. The chromosomes migrate and align singly with the metaphase plate by action of the kinetochore microtubules

   4. Drugs like colchicine will interfere with spindle function, arresting cells at metaphase

3. Anaphase:

   1. Centromeres divide, sister chroamtids are separated to form daughter chromosomes which are pulled apart to opposite poles of the cell with their centromeres leading, sister chromatids pulled along behidn them in a characteristic ‘V-shape’ pattern

   2. poles of cells move further apart as polar microtubules slide past one another, elongating the cell

   3. special motor proteins are involved in the abrupt and rapid movement of centromeres to opposite poles of the cell

   4. At the end of anaphase, 2 poles have equal and complete set of chromosomes

4. Telophase

   1. occurs are all the daughter chromosomes are at their respective poles

   2. chromosomes uncoil, decondensing into chromatin

   3. nucleolus and nuclear envelope reform, causing the two nuclei to take on the appearance of interphase

   4. microtubules disassemble, with one pair of centrioles ending up in each daughter cell

5. Cytokinesis: division of cytoplasm to form 2 daughter cells by result of formation of a cleavage furrow

   1. Simultaneously occuring with telophase

   2. forms a shallow groove in cell surface near metaphase plate

   3. contractile ring of microfilaments conracts, causing farrow to deepen until it pinches into 2 daughte rcells

   4. in plant cells, division of cytoplasm occurs by growth of cell plate where vesicles from GA will migrate and fuse in the middle of the cell to form the cell plate

Describe the meiotic cell cycle.

Interphase:

1. G1 phase: cells increase in size, acquire ATP, synthesis appropriate organelles & proteins

2. S phase: Each DNA molecule undergoes semi-conservative DNA replication, giving rise to 2 genetically identical daughter DNA molecule. Chromosomes only replicate once

3. G2 phase: Cells increase in size…, pair of centrioles replicate, mitoic spindle starts to form

Meiosis I

1. Prophase I

   1. nuclear envelope disintegrate, nucleolus disappears

   2. chromosomes condense into chromatin

   3. centrioles migrate to opposite poles of celll, mitoic spindle starts to form

   4. 2 homologous chromosomes pair up to form bivalent, where homologues are bridged by synaptonemal complex, bringing the genes of each chromosome into precise alignment

   5. Formation of chiasmata between 2 non-sister chromatids of homologous chromosomes

   6. Crossing over occurs between non-sister chromatids of homologous chromosomes, undergoing exchange of alleles to form new combination of paternal and maternal alleles on each chromatid, hence the sister chromatids are non-genetically identical, forming recombinant chromatids

2. Metaphase I

   1. Centriole pairs are positioned at opposite poles of the cell, with shortening & thickening of chromosomes at maximum

   2. recombinant sister chromatids are joined at centromere of each chromosome, with kinetochore microtubules attached to kinetochores at the centromeres of 1 chromosome of each bivalent

   3. independent assortment of paired homologous chromosomes at metaphase plate, where there is random orientation of each bivalent independent of other bivalents

      1. random distribution of parental and materal alleles into each gamete, increasing genetic variation

      2. alignment of paired homologous chromosomes at metaphase plate ensures equal distribution into daughter cells

3. Anaphase I

   1. 2 homologous chromosomes of each bivalent separate, pulled to opposite poles of the cell with centromere leading, producing characteristic ‘V’ shape pattern

      1. equal distribution of chromosomes into each daughter cell

   2. centromeres remain intact, sister chromatids remain attached to each other

   3. segregation: disjunction, failure to separate is non-disjunction

4. Telophase I

   1. microtubules disassemble, chromosomes decondense into chromatin form by uncoiling

   2. cell organelles become evenly distribute dbetween 2 poles of parent cells, pair of centrioles end up in each daughter cell, nuclear envelope & nucloelus reform

   3. nuclei formed are haploid since chromosome number & ploidy level already halved

5. Cytokinesis I occurs simultaneously with telophase I, forming 2 haploid daughter cells

Meiosis II

1. Interphase II: very short/non-existent, as meiosis II occurs almost immediately after meiosis I, centrioles replicate, no further DNA replication

2. Prophase II

   1. nuclear envelope disintegrate, chromatin condense into discrete chromosomes, centrioles move to opposite poles of teh cell

   2. new spindle fibres appear, arranged at right angle to spindle of meiosis I

3. Metaphase II

   1. Centrioles positioned at opposite poles of the cell, with shortening & thickening of chromosomes at maximum

   2. 2 sister chromatids joined at centromere of each chromosome, kinetochore attached to centromere of chromosome

   3. chromosomes migrate and align singly at metaphase plate by action of kinetochore microtubules, which is perpendicular to that of meiosis I

   4. independent assortment of chromosomes at metaphase plate, allowing for random distribution of non-sister chromatids, independent of the other

      1. ensures equal distribution of chromosomes to each gamete, ploidy level is haploid

   5. Anaphase II
      centroemres divide, 2 sister chromatids separate to form daughter chromosomes

   6. which are pulled to opposite poles of te cell with centromeres leading, sister chromatids pulled along behidn them in ‘V’ shape pattern

   7. polar microtubules slide past one another, elongating the cell

4. Telophase II

   1. microtubules diassemble, chromosomes decondense into chromatin

   2. cell organelles are evenly distributed between 2 ples of parent cell, one pair of centrioles ends up in each daughter cell

   3. nucleolus and nuclear envelope re-form

   4. nuclei formed are haploid

5. Cytokinese II: produces 4 haploid, genetically non-identical daughter cells

Explain the significance of mitosis.

1. Ensure preservation of genetic stability across generation of cells: Mitosis produces 2 daughter cells with same number of chromosomes, as semi-conservative DNA replication give rise to genetically identical daughter DNA molecule, and daughter chromosomes are distributed equally to daughter cells during anaphase

   1. No variation of genetic information during mitosis, so daughter cells are genetically identical to parent cell, hence genetic stability

2. Growth: new cells formed are genetically identical to existing cells to carry out the same functions

3. Repair: damaged cells replaced by exact copies of original to allow restoration to former condition

4. Regeneration of missing parts: cell replacement occurs to a certain extent in multicellular organism

5. Asexual reproduction: allows preservation of favourable traits down generation, division of one cell reproduces whole organisms for unicellular organisms

Explain significance of meiosis.

1. Sexual reproduction:

   1. Meiosis results in production of gametes, with ½ the number of chromsomes as compared to a parent cells

   2. If this does not occur, fusion of gametes during subsequent fertilisation will result in doubling of chromosome number for each successive generation

   3. Hence, meiosis stabilises and maintaisn a constant chromosome number in every generation of a species

2. Genetic variation: Meiosis allows for new combinations of alleles in gametes leading to genetic variation in the genotypes & phenotypes in offspring

   1. Crossing over of aleles during prophase I of meiosis to allow for new cobination of paternal & maternal alelles in chromatids

   2. Independent assortment in metaphase I & II to allow for random distribution of parental & maternal alleles to each gamete

   3. Random fusion of gametes during fertilisation, each with different combination of parental and maternal chromosomes

Compare dividing and non-dividing cells.

1. Dividing cells are transcriptionally inactive while non-dividing cells are transcriptionally active

2. Dividing cells have tightly coiled DNA as discrete chromosomes, while non-dividing cells have DNA loosely coiled and uncondensed as chromatin

3. In dividing cells, nucleolus and nuclear envelope is absent, while in non-dividing cells, nucleolus and nuclear envelope is present.

Compare meiosis and mitosis.

1. Interphase and semi-conservative DNA replication precedes both processes

2. In prophase of mitosis, homologous chromosomes remain separate, while in prophase I of mitosis, homologous chromosomes are paired up to form bivalents

3. Formation of chiasma between non-sister chromatids during prophase I of meiosis occurs, while there is no formation of chiasma during prophase of mitosis

4. Pairs of homologous chromosomes align along metaphase plate during metaphase I of meiosis, whereas chromosomes align singly along metaphase plate in metaphase of mitosis

5. Homologous chromosomes separate in anaphase I of meiosis, whereas sister chromatids separate during anaphase of mitosis

6. No separation of centromere in anaphase I of meiosis, while centromeres divide in anaphase of mitosis

7. Meiosis gives rise to 4 haploid genetically non-identical daughter cells while mitosis give rise to 2 genetically identical diploid daughter cells

8. Meiosis is reduction cell division, mitosis is equatorial division

9. Genetic variation occurs in meiosis but not in mitosis

Describe the characteristics of a cancer cell.

1. High rate of cell division in the absence of growth factors

2. Genome instability caused by increased rate of accumulation of mutations

3. Replicative immortality

4. Loss of anchorage dependence, as they do not need contact with suitable substratum to replicate

5. Lack of contact inhibition and density-dependent inhibition

State the cell cycle checkpoints, and how the dsyregulation of said checkpoints can lead to cancer.

1. G1 phase: Assessment of cell growth

   1. checks for presence of growth factors which are needed to stimulate cell division

   2. Checks for DNA damage and cell size, imitating apoptosis if there is irreparable DNA damage

   3. Checks that there is sufficient nutrients in the cell

2. G2 phase: Assessment of DNA replication

   1. Check that DNA has successfully replicated, initate apoptosis if irreparable DNA damage

   2. Once passed, proteins will signal cell to begin molecular processes allowing mitoic division

3. Metaphase: Assessment of mitosis

   1. Checks for successful formation of spindle fibers, and the attachment of fibres to kinetochores of chromosomes

      1. Mitosis arrested if spindle fibers not formed/attachment inadequate

   2. Ensures successful separation of DNA into 2 daughter cells

The dysregulation of cell cycle checkpoints at

1. G1 / G2 phase will result in the cell cycle continuing to progress even when there is no repair of damaged/incorrectly replicated DNA, resulting in further accumulation of mutations in cancer critical genes

2. M checkpoint: spindle fibres might not be attached properly to kinetochores of chromosomes, resulting in chromosoaml abberrations which may result in accumulation of mutations in cancer-critical genes

Describe how the p53 gene carries out its function.

p53 gene codes for the p53 protein, which when activated, acts as a transcription factor to bind to specific control elements of DNA to promote the transcription of genes encoding proteins that work to:

1. Activates DNA repair proteins when DNA sustains damage

2. Initate apoptosis if irreparable DNA damage

Arrest cell cycle at G1/2 regulation point,

p21 protein stops cell cycle by binding to proteins involved in cell cycle progression, such as CDKs

Describe the loss of function mutation in tumour suppressor genes, and why it results in a recessive allele.

Gene mutation occurs in nucleotide sequence coding for tumour suppressor gene, resulting in a loss of function mutation caused by missense or silent mutation. However, the LOF mutation needs to occur for both copies of the tumour suppressor gene, as with 1 mutation, the other copy of the tumour suppressor gene will still produces sufficient quantities of the normal gene products that the effects of mutation are masked.

Describe the functions of proto-oncogene.

Proto-oncogene encodes gene products which promote normal cell division, as the following:

1. Growth factors

2. Growth factor receptor

3. Protein kinases

4. Inhibitors of apoptosis

5. Transcription factors to regulate transcription of genes that induce cell proliferation

Describe the function of ras gene, and hence how its ability to carry out its function is affected by a gain in function mutation.

1. The activated ras protein relays signals from growth factor receptor to a series of protein kinases

2. The last protein kinase of signal transduction pathway activates transcription of genes encoding proteins that stimulate cell division

3. Pathway is normally activated only when the growth factor binds to the receptor

However, a gain in function mutation can lead to the ras protein being over expressed or the production of a hyperactive ras protein, which has a 3D conformational change in the ras protein shape, resulting in

1. GTP remains bonded to ras to form ras-GTP complex, resulting in a constant active site evening the absence of growth factors

2. Increased cell signalling, stimulating the cell cycle for increased cell division

Outline the multi-step model of cancer progression.

1. Accumulation of Mutations: Genesis of cancer requires gradual accumulation of several independent mutations in cancer critical genes, including at least 2 LOF mutations in tumour suppressor genes and 1 GOF mutation in proto-oncogene, in a single cell lineage

2. Activation of telomerase: mutations leading to the reactivation of telomerase, allowing the evasion of the Hayflick limit and hence apoptosis, allowing the cell to proliferate indefinitely

3. Angiogenesis: the formation of new blood vessels, allowing the supply of O2 and nutrients to the tumour and removing toxic waste products, allowing for continued cell division and increased in tumour size, and provides pathway for cancer cells to spread to other sites of the body

   1. Tumour cell releases angiogenesis-activating proteins, attracting endothelial cells & promoting proliferation

   2. Endothelial cells secrete protein-degrading enzymes (MMPs), which breka down blood vessel wall and components of extracellular matrix, allowing endothelial cells to be organized into new networks of blood vessels

4. Metstasis

   1. Mutation resulting in the ability of cancer cells to invade surrounding tissues and penetrate through the lymphatic and blood vessel wall to enter the circulatory system annd travel to distant sites, allowing the formation of secondary tumours at distant sites from primary sites

Describe the causative factors of cancer.

1. Chemical carcinogens:

   1. PAHs (polycyclic aromatic hydrocarbons) are produced by smoking and high-temperature cooking methods, which also produces heterocyclic amines (HCAs), both of which bind to DNA

   2. cause mistakes in DNA synthesis —> gene mutations

   3. forms adducts at several sites of p53 gene, preventing production of functional p53 protein

2. Ionising/UV radiation increases rate of mutations

3. Age: cancer results from accumulation of mutations which occur throughout life, so longer we life more likely we are to develop cancer

4. Genetic predisposition: inherit mutation in cancer-critical genes, bringing individual loser to accumulating necessary mutations for development of cancer

5. Loss of immunity: where immune system is suppressed by drugs, unable to detect & destroy cancerous cells due to absence or inadequate number of immune cells

6. Viral infection as tumour viruses can integrate into DNA of host cells, turning host cells into tumourigenic cells

   1. Inactive tumour suppressor genes/convert proto-oncogene into oncogene

   2. direct expression of viral protein which inactive p53 to render host cell more susceptible to cancer

   3. introduce oncogene into normal cell via retrovirus

In case of a donated trachea, explain why all the cells are removed from the donor trachea, and stem cells are taken from the body of the patient to form the trachea using the donated collagen.

1. The need to avoid stimulation of immune response that would lead to rejection of the donated trachea, which could result in

2. continued need to take immunosuppressive drugs in the long term

3. Donor cells may also be infected with virus / bacteria, which could infect host cell

Explain why stem cells need to be treated with chemicals to stimulate proliferation.

1. Chemicals act as signal molecules to stimulate mitosis, allowing for proliferation

Describe the chracteristics of a stem cells.

1. Stem cells are unspecialized cell types, with no tissue-specific structures that allow it to form specialised functions

2. Stem cells are capable of dividing and long-term self-renewal by mitosis, as they replicate many times with resulting daughter cells continuing to be unspecialised

3. Stem cells can give rise to Specialised cell types by undergoing cell differentiation, triggered by internal or external signals

Define stem cell potency.

Stem cell potency refers to he range of cell types ht a stem cell can give rise to, determined by the number of possible developmental pathways it can take via cell differentiation.

Differentiate between totipotent, pluripotent and multipotent cells.

1. Totipotent stem cells consist only of zygotic stem cells, existing as fertilized egg and the first few cells produced as zygote undergoes rapid mitosis

   1. capable of forming extra-embryonic membranes and embryo

   2. has the largest possible no. of developmental pathways

2. Pluripotent: descend from totipotent stem cells, making up inner cell mass of blastocyst, and have ability to give rise to cell types that form the 3 germ layers (ectoderm, mesoderm, endoderm)

   1. do not have developmental potential to make differentiated cells that form extra-embryonic membranes

3. Multipotent: descend from pluripotent stem cells that differentiated into limited number of cell types (e.g. blood stem cells)

Describe the functions of embryonic stem cells.

Embryonic stem cells are derived from the inner cell mass of blastocyst, and

1. capable of undergoing unlimited number of symmetrical divisons without differentiating

2. exhibit and maintain stable, full, normal complement of chromosomes

3. clonogenic, with each ESC giving rise to colony of genetically identical cells

4. give rise to differentiated cell types derived from all 3 primary germ layers

5. capable of developing into all fetal tissues during development

6. easy to obtain pure, and can be cultivated in large numbers

Describe functions of adult stem cells.

Adult stem cells are undifferentiated cells found among differentiated cells in a tissue/organ

1. Maintain/repair the tissue in which they are found

2. Replace cells that die because of injury/disease

3. are able to remain undifferentaited for prolonged periods of time

4. rare, very small number of adult stem cells in each tissue

5. capable of giving rise to fully differentiated cells that have mature phenotypes, are fully integrated into eh tissue and can carry out specialised functions

Describe the function of hematopoietic stem cells.

Hematopoiesis is blood formation, with is a good example of cell differentiation as:

1. blood cells at all stages are relatively accessible

2. blood cells can be grown in culture

Hematopoietic stem cells replace blood cells, of

1. lymphoid lineage: derived from common lymphoid progenitor cells, produces lymphocytes, including 2 antigen-specific cell types of immune system (B & T lymphocytes)

2. myeloid lineage: derived from common myeloid progenitor cells, giving rise to the rest of white blood cells which all derive from bone marrow

3. erythroid lineage: yield erythrocytes and megakaryocytes

Distinguish between sister chromatids and homologous chromosomes.

1. Sister chromatids genetically identical, homologous chromosomes are not

2. Sister chromatids are attached at the centromere, homologous chromosomes are unattached but pair up during prophase I of meiosis

3. Sister chromatids are separated during anaphase II of meiosis while homologous chromosomes separated during anaphase I of meiosis

Explain why meiosis is important for continued existence of species.

1. Enables genetic variation in gametes, fusion of gametes giving rise to genetically variable individuals, better adapt to environmental changes

2. haploid gametes fuse during fertilization to give a diploid zygote, maintainence of no. of chromosomes in each successive generation

Vinblastine disrupts the formation of spindle apparatus. Explain how vinblastine acts as an anti-cancer drug.

1. Growth of tumour is caused by mitosis

2. Spindle apparatus is required for stages of mitosis

3. Hence,

   1. cannot attach to centromeres in prophase

   2. chromosomes cannot align singly with metaphase plate

   3. division of sister chromatids not possible In anaphase

4. mitosis stops, prevent tumour cells from further mitosis

Explain which mutations of the following has the most serious consequences for the structure of the protein:

1. Single-base insertion

2. Single-base substitution

3. Single-base deletion

Insertions and deletions results in frameshift mutations, causing all amino acids after mutation to be different, hence 3D conformational change

Substitutions may change only 1 amino acid, hence having a lower impact on the structure of the protein.