Week 3 - molecules Flashcards
stem cell differentiation
asymmetric division - produce one identical daughter cell and one second daughter cell with different genetic instructions (will become a progenitor or precursor cell)
cell potency
cells ability to differentiate into other types of cell - more cells it can differentiate into, the greater its potency
four types of cell potency
totipotent - any cell type of adult body and embryonic membrane
pluripotent - any cell type in adult body
multipotent - tissue-specific cell type of adult body
unipotent - one specific type of adult body tissue cells
hierarchy of a stem cell potency using haematopoeitic stem cells as example
fertilised egg - totipotent stem cells - blastocyst containing pluripotent stem cells - haematopoeitic stem cells - blood cells
haematopoeitic stem cells
generate blood and immune cells
found in bone marrow
can self renew
can differentiate into RBCs, WBCs and platelets
what are induced pluripotent stem cells
adult somatic SCs that have been reprogrammed back to pluripotency - meaning they can be turned back to SCs and differentiate into other cell types
how to make induced pluripotent stem cells
Treated with transcription factors (OCT-3/4, SOX2, c-Myc and KLF4) to switch on genes to induce and maintain pluripotency
describe iPSCs
stem cells markers self-renewal capability differentiation potential the ability to be cultured (grown in lab) the ability to form all the germ layers
where are human embryonic stem cells derived from
inner cell mass of blastocyst
cons of using adult stem cells instead of embryonic SCs
more difficult to isolate them as there is few in number and it is difficult to keep them proliferating in culture
theory of cancer stem cells
stem-like cells within tumours
exhibit characteristics of both SCs and cancer cells
Defined by ability to generate more stem cells (self-renewal) and to produce cells that differentiate
Have ability to seed tumours when transplanted into an animal host
stem cell potential uses
tissue repair drug screening vehicles for gene therapy regenerative medicine (bone marrow transplants and HoloclarR) develop cartilage treatment current research into making new blood
examples of adult tissue stem cells and their function
haemopoeitic stem cells generate blood and immune cells
mesenchymal stem cells can make different cells belonging to skeletal tissues
genome
complete set of genetic instructions
transcriptome
complement of genes that are actually transcribed
housekeeping genes
genes transcribed in every cell type
do all cells transcribe the same genes
Different cells transcribe different subsets of genes, and it’s a subset of genes that you transcribe into message RNA that starts to give the cell its identity or it’s phenotype
proteome
entire set of proteins that can be expressed by a genome
amino acid structure
Amine group and carboxyl group
R is a variable chemical group
Link up via a condensation reaction – water is removed from amino acids and they join as a peptide bond
examples of post-translational modifications of proteins
Many proteins are glycosylated - help interacting with partner proteins, protect them, increase half life, important for orientation
Many are phosphorylated – receptor signalling, intracellular communication, control of enzyme function
to begin translation, how does the ribosome know which methionine to bind to
little sequences of bases called kozak sequnces help – when ribosome sees kozak sequence that tells ribsome the next methionine codon is the start
locations of protein synthesis
Smooth ER involved in lipid synthesis and metabolism
Rough ER involved in protein secretion
translate the protein in the centre of the endoplasmic reticulum and then the proteins, bud off into little vesicles, they can get decorated in the Golgi apparatus and then they could be secreted by fusing with the membrane
Soluble intracellular proteins are synthesised by free ribosomes
how do newly synthesised proteins know where to go
they carry amino acid sequences (signals) that tell them where to go
signal peptides is used for entry into ER and a nuclear translocation signal is used for proteins going to the nucleus
explain what is meant by the four different protein structures
primary structure - amino acid sequence
secondary - amino acids folded into structures such as alpha helixes or beta pleated sheets
tertiary - proper folding of protein into final shape
quartenary - coming together of subunits to form the overall functional protein
diseases caused by protein mutations
sickle cell anemia - Mutation in the beta-globin gene - 1 codon changes – valine is coded for instead of glutamic acid - Changes the whole structure of protein
cancer - RAS can become hyperactive
haemostasis
the stopping of blood flow which helps to prevent blood loss
three phases of haemostasis
vasoconstriction
formation of a platelet plug
coagulation
haemophilia
patients lack a clotting factor which leads to impaired ability to form blood clots
vasoconstriction
blood vessels narrow to reduce blood flow to the injured area
formation of a platelet plug
Disruption to the endothelium activates platelets (bc collagen is exposed)
Activation of platelets results in a shape change and also results in the release from secretory granules - released products make platelets sticky
sticky activated platelets attract one another and adhere forming a clump
what is essential for the intrinsic and extrinsic pathway
calcium
coagulation process (final common pathway)
extrinsic and intrinsic result in prothrombinase activating prothrombin to form thrombin
thrombin facilitates formation of insoluble fibrin from soluble fibrinogen - leads to gel like consistency of clot - lattice of fibrin forms which traps blood cells and forms a soft clot
cross links form between fibrin strands which leads to a more stable hard clot
fibrinolysis
plasminogen circulates in plasma and as clot forms it becomes trapped - it is activated by a serine protease called tissue plasminogen activator (tPA) - tPA converts plasminogen to plasmin which then breaks down the fibrin mesh
components of blood
RBCs, plasma, platelets, WBCs
function of RBCs
carries oxygen from lungs to systemic tissues, carries carbon dioxide from tissues to lungs
assists in the buffering of acids and bases
structure of RBCs and how it relates to their function
biconcave shape maximises surface area to volume ratio to maximise O2 exchange
flexible and has a bell shape so it can pass through small blood vessels
no nucleus to maximise space for oxygen
Deoxy-haemoglobin has a relatively low affinity for oxygen, but when one molecule binds to a single heme, the oxygen affinity increases, allowing the second molecule to bind more easily, etc.
function of platelets
small cell fragments that are essential component of coagulation system
function of plasma
fluid that carries blood components throughout body - delivers nutrients, hormones and proteins to parts that need it
helps remove waste from the body
differences between the intrinsic and extrinsic pathway
intrinsic is slower and involves more steps
extrinsic is initiated by tissue factor and intrinsic is initiated by activated platelets