Genes And Health Flashcards
What is the function of mucus?
- Traps foreign particles (dust, bacteria) and prevents them from entering the airways
- moisturises inhaled air (to aid diffusion)
What are the properties of gas exchange surfaces in living organisms?
- large sa/v ratio
- thin surface - short diffusion distance
- high concentration gradient
Ficks law - calculating rate of diffusion
The rate of diffusion is inversely proportional to the thickness of the gas exchange surface
rate of diffusion directly proportional to
SA x difference in conc
——————————
diffusion distance
How CF affects the respiratory system?
(breathing difficulties due to reduced gas exchange)
- less air can be breathed out - over inflation of the lungs causes elasticity of lungs decreases
- mucus blocks bronchioles: fewer alveoli available for gas exchange
- mucus fills alveolus: longer diffusion distance
- (Harder to breathe, exercise)
Gas exchange on outer surface of a land-living (terrestrial) organism?
- Outer surface for protection, not gas exchange
- high water content in mammal compared to the surrounding air, so would dry out
- outer layer is very thick, long diffusion distance ensures slow gas exchange
- have internet gas exchange surfaces to reduce evaporation losses
Multicellular aerobic respiration why?
Because they require a lot of energy and aerobic produces 19 times more ATP (adenosine triphosphate) per molecule of glucose
Gas exchange in other organisms:
Unicellular organisms: build up of CO2 - high conc gradient and thin surface membrane
Insects: hard exoskeleton unsuitable for gas exchange, lack of transport system - gas exchange through outer surface (short diff distance)
& tracheoles - large SA and they also contain fluid so glasses diffuse efficiently
How are alveoli adapted for efficient gas exchange?
- both endothelium and epithelium are 1 cell thick so short diffusion distance
- constant flow of blood and air flow from breathing so steep concentration gradient is maintained
- folded shape of alveoli, many alveoli and capillaries - large SA/v ratio
- pulmonary surfactant prevents the alveoli from collapsing
- moisture dissolves gases to allow diffusion + prevents lung tissue drying out
- close to capillaries - short distance
- smoking: destroys alveolar walls, decreased SA for gas exchange, decreased diffusion rate
Primary structure of proteins:
= The linear sequence of the amino acids in a protein
Secondary structure of proteins:
= Regular 3D structure formed due to hydrogen bonds between the H and O of PEPTIDE BONDS
Secondary structure - Alpha Helices
polypeptide chain wound round to form helix (many H bonds so have very strong, stable structure) - held together by hydrogen bonds running parallel with the long helical axis
Secondary structure - Beta pleated sheet
Polypeptide chain zig zags back and forward forming a sheet of anti parallel strands
Held together by H bonds between peptide bonds
Tertiary structure of proteins:
= 3D structure of the whole peptide chain, formed by hydrophobic interactions,
hydrogen bonds,
ionic bonds,
disulphide bonds between R GROUPS
Bonds involved in making up tertiary structure from weakest to strongest:
hydrophobic interactions between R groups
hydrogen bonds (between H and O)
ionic bonds between charged R groups
disulphide (covalent) bonds between cysteine R groups
Quaternary structure of proteins:
= The 3D structure of several polypeptide chains joined together
Conjugated proteins:
= proteins that are joined to other non-protein molecules (known as prosthetic groups e.g the Haem in Haemoglobin)
Globular proteins:
Proteins with a complex tertiary (sometimes quaternary) structure
- folded into spherical shapes (hydrophobic parts on the inside)
- soluble (hydrophilic parts on the outside)
• often small
E.g enzymes, antibodies, hormones
-insulin (51 aa)
Fibrous proteins:
= proteins that have little/no tertiary structure
- form long fibres made of several polypeptide chains
- insoluble
- often large
- strong
-structural role (e.g tendons)
-collagen (>1000 aa)
& Collagen has repeating sequences of amino acids
Why may the increase in temperature increase the length of the secondary structure of the polypeptide?
Increase in kinetic energy, more vibrations within the molecule that could break the hydrogen bonds - molecule unwinds
What surrounds the goblet cells and what are they attached to?
Ciliated columnar epithelial cells - attached to basal membrane that holds them in place
What is the fluid mosaic model?
1972 Singer and Nicholson’s membrane model:
Proteins are through the membrane, not holding phospholipids in place
• by increasing ionic strength of solutions or by adding protease-containing detergents, some proteins can be removed from membrane
What are the components of a phospholipid?
Hydrophilic phosphate heads face towards the solution (& polar)
Hydrophobic fatty acid tails face away from the solution (& non-polar)
What’s glycocalyx?
Protective role on membrane (carb part of glycolipid)
Why is it called the fluid mosaic model?
Fluid - because of the lateral movement of lipids and proteins through the bilateral
Mosaic - composed of many different macromolecules
What are other components of membranes?
Peripheral protein (cellular communication - on the surface), cholesterol, integral protein (on inside layer), integral transmembrane protein - channel proteins (across whole bilayer)
Increase membrane fluidity:
More unsaturated (double bonds, bends in chains) fatty acids, phospholipids less tightly packed (more movement possible)
Decreasing membrane fluidity:
more cholesterol, less fluid- prevents movement of phospholipids
(But if there is too little cholesterol, it is too fluid- disrupts structure)
What affects the degree of fluidity of cell surface membranes?
The length of the fatty acid side chains (longer - less fluid)
The proportion of the fatty acids which are saturated (higher percentage of saturated - lower fluidity)
The steroid (cholesterol) content (higher steroid content - lower fluidity)
PASSIVE transport definitions:
Diffusion: the movement of molecules from an area of high to low concentration
Facilitated diffusion: the movement of molecules from an area of high to low concentration via a carrier protein (across a membrane)
Osmosis definition:
The movement of water molecules from high to low water potential across a partially permeable membrane
Active transport:
= movement from low to high concentration via carrier proteins and using energy from ATP
Endocytosis:
= uptake of molecules starting with invagination of the cell membrane and resulting in the formation of vesicles (bulk transport into cell)
‼️ requires energy
Exocytosis:
= when vesicles fuse with the cell memes be and release their contents (bulk transport out of the cell)
‼️ requires energy
Hypotonic solution:
= lower solute concentration than inside cell
(When a plant/animal cell is in this kind of bathing solution, water moves into the cell by osmosis, leaving the cell lysed (in an animal cell) or turgid (in a plant cell ‼️ this is normal for a plant)
Isotonic solution:
= same solute concentration as inside cell
no net movement of water (plant flaccid, normal for an animal)
Hypertonic solution:
= higher solute concentration than inside cell
(When a plant/animal cell is in this kind of bathing solution, water moves out of cell/vacuole by osmosis, leaving the cell shrivelled (in an animal cell) or plasmolysed (in a plant cell)
Channel and carrier proteins:
Channel proteins are for polar molecules eg ions
Carrier proteins are for larger molecules eg glucose
Mucus formation in healthy people (with excess water)
Na+ actively pumped across basal membrane
Na+ diffuse through sodium channels in the apical membrane
Cl- diffuses down electrical gradient
Water moves out of cells by osmosis due to high salt conc into the tissue fluid
Water moves out of mucus by osmosis
Mucus formation in healthy people (with too little water)
Cl- actively pumped into cell from tissue fluid across basal membrane
CFTR channel is open and causes Na+ channel to close. Cl- diffuses through the open CFTR channel
Na+ diffuses down electric gradient into the mucus
Elevated salt conc in mucus draws water out of the cell by osmosis. Water diffuses into mucus + makes it more running
Water is drawn into cell from tissue fluid by osmosis
Enzymes:
Globular proteins that act as biological catalysts and reduce activation energy
Enzymes that catalyse reactions inside cells:
Intracellular enzymes
Enzymes that catalyse reactions outside cells:
Extracellular enzymes
Cofactors:
= non-protein chemical compounds that are bound to enzymes + required for enzyme action
coenzymes - loosely bound cofactors (vitamin c + metal ions)
prosthetic group - tightly bound cofactors (eg heme group)
Competitive inhibitor:
= compete with substrate for active site
non- competitive inhibitor
= bind to allosteric site + influence shape of active site
turnover number:
= number of substrate molecules transformed by one molecule of enzyme per second
Substrate and enzyme concentration as an affect on rate of reaction of an enzyme:
For either:
1) lower concentration, not all active sites occupied/few ES complexes formed, slow rate of reactive
2) high concentration - (/more active sites➡️) more ES complexes, higher rate
3) IF more substrate than enzyme, all active sites occupied, increasing substrate has so affect - max rate of reaction (V max) ➡️ depends on turnover number of enzyme
3) more enzyme than substrate, increasing enzyme conc has no more affect, substrate has become limiting factor
Active site:
Part of the folded protein where the substrate(s) bind
When all the active sites are occupied - enzyme is saturated
why measure the initial rate of reaction?
As reaction goes on, there is a decreasing about of substrate but the concentration of enzyme stays the same. This lessons the chances of a collision between a substrate molecule and an enzyme.
➡️ at the initial rate, most valid measurement, when rate of reaction is under the desired conditions, (much higher amounts of substrate than product)
How can CF cause lung infections?
- thick, dry mucus lines airways and traps bacteria but too sticky to be moved by cilia ➡️ inflammation + infection
- low o2 levels in mucus: anaerobic bacteria thrive
- WBC fighting bacteria die + release DNA making mucus stickier
How does CF impair the functioning of the digestive system?
Thick sticky mucus in the pancreatic duct + small intestine
➡️impaired digestion
- digestive enzymes made in pancreas can’t reach small intestine
- reduced digestion of food
- reduced nutrients uptake (longer diffusion pathway + reduced SA)
➡️ damage to pancreas
- trapped enzymes damage pancreas
- islets of langerhans might be damaged + insulin production affected
How does CF impair the functioning of the reproductive system?
- infertility
- thick sticky mucus in the reproductive system
FEMALE - TSM blocks cervix and oviducts
-sperm cannot get past mucus plug
MALE - sperm duct might be missing/blocked by TSM
- reduced number of sperm can leave testes (reduced sperm count)
- reduced fertility
How does CF affect sweat production?
• in healthy people, (sweat = salty water made in sweat glands) salt is reabsorbed out of sweat duct into cells (Cl- via CFTR, Na+ follow by diffusion)
• but in CF sufferers, in the absence of functional CFTR, Cl- and Na+ are not reabsorbed + instead are lost in sweat
- conc of body fluids changes (may affect the heart)
Why may an enzyme have a low pH optimum? (Acidic)
Eg pepsin catalysed reactions in the stomach in acidic conditions
What is the structure of a mononucleotide?
Deoxyribose/ribose (pentagon as pentose sugars) linked to a phosphate (circle) and a base
What are the general structures of DNA/RNA?
polynucleotides composed of mononucleotides linked through condensation reactions
Which bases have a single ring structure?
Thymine/Uracil and Cytosine
PYRIMIDINES
Which bases have a double ring structure?
Adenine and Guanine
PURINES
What are the steps of nucleotide formation?
Sugar joins base in condensation reaction = nucleoside (base + sugar)
phosphate joins sugar side of nucleoside in condensation reaction = nucleotide
What is a phosphodiester bond?
The bond between the OH and H from one sugar and the adjacent phosphate when they form the backbone of DNA in a condensation reaction.
Which bases form 3 or 2 hydrogen bonds?
A … T with 2 hydrogen bonds
G … C with 3 hydrogen bonds
Differences between DNA and RNA?
the sugar they contain
the bases
the structure - RNA is single stranded
the length - RNA is made of shorter strands and DNA is very long
the location - DNA is always in the nucleus, RNA is made in nucleus but found throughout the cell
the amount - DNA amount constant in cells, RNA varies from cell to cell
stability - DNA is chemically very stable, RNA is chemically unstable
Define the genetic code:
The DNA code that ensures amino acids are arranged in the correct sequence in proteins
What is the nature of the genetic code:
Triplet code: 3 bases (a codon) codes for 1 amino acid
It’s degenerate: one amino acid can be coded for by more than one codon
Non-overlapping (each codon is read separately)
ALSO ➡️
Universal: same code in all organisms
TAA, TAG, TGA (the 3 stop codons) don’t code for an amino acid
Define transcription and where does it occur?
The copying of DNA into messenger RNA (mRNA)
-it occurs in the nucleus
What catalyses transcription?
RNA polymerase
What are the steps in transcription?
- RNA polymerase binds to promoter region
- RNA polymerase unwinds double helix and starts to transcribe DNA sequence on the anti-sense (template) strand into RNA sequence through complementary base pairing. ➡️ free nucleotides line up by complementary base pairing
- RNA transcript is made (and is same as coding strand with U instead of T)
- after RNA polymerase reaches termination point, transcription stops and RNA polymerase detaches
- RNA sequence is spliced (introns are removed) and processed
- RNA is translocated out of nucleus via pores in the nuclear envelope
Define translation and where does it occur?
Translating mRNA sequence into an amino acid sequence
Occurs on ribosomes in the cytoplasm or on the rough endoplasmic reticulum
What are the steps in translation?
- Amino acid binds to corresponding tRNA
- mRNA attaches to ribosome and ribosome moves along to the AUG (start codon). ribosome loads tRNA with complementary anticodon UAC.
- Ribosome moves a long and loads the next tRNA. adjacent amino acids join via a peptide bond (catalysed by peptide synthetase). when it loads the third tRNA, it releases the first one
- ribosome reaches stop codon and release factor stops translation. ribosome separates- polypeptide chain complete
What is a polysome?
mRNA with several ribosomes attached. several ribosomes can bind to the same mRNA so that several polypeptide chains are synthesised at the same time
what is the structure of tRNA
Is folded with a tertiary structure and has hydrogen bonds.
Has anticodons (at bottom) Has an amino acid binding site (at the top)
What structure is mRNA?
primary structure
What are the steps of DNA replication?
- DNA helicase unwinds the DNA double helix
- two strands are separated as H bonds break
- Each parent strand is a template for a new DNA strand. DNA polymerase pairs new nucleotides with complementary nucleotides (nucleotides join together forming phosphodiester bonds)
- two identical new DNA strands are exposures and they rewind into a helix
Why is replication considered ‘semi-conservative’
Each new DNA molecule has one strand of original parent DNA and one new strand
What were the theories about DNA replication and who proved the right one?
Semi-conservative
dispersive - 2 DNA molecules made randomly of 50% new and 50% old DNA
conservative - one molecule completely old and one completely new
Meselson and Stahl’s experiment
How can errors in DNA replication lead to mutations?
Eukaryotic DNA polymerase makes 1 mistake in every 10-100k base pairs but it has ‘proof reading’ enzymes to correct mistakes
So ~1 mistake in every 10 mil base pairs per cell division
mutagens can lead to chemical changes in bases, errors during replication
What are the types of gene mutations?
Point mutation - change in a single base(nucleotide)
Frame shift mutation - the reading frame changes and results in a different protein sequence (insertion/deletion of a nucleotide)
Substitution - a nucleotide is replaced by another base
Inversion - two nucleotides are swapped
What are the names given to the affect in the sequence of types of mutations?
Silent mutation - no change in amino acid sequence (bc it’s a degenerate code)
Missense mutation - change in the amino acid sequence
Nonsense - premature stop codon ➡️ non functional protein
How can a mutation be inherited?
Somatic mutation- mutation not passed on
Germ line mutation - in germ cell, passed on ➡️ mutation would be in every body cell and 50% chance of them in sex cells (because 1 of each chromosome)
How can a genetic disease suddenly appear in a family with no previous history of the disease?
By a random mutation in the genes causing a faulty protein to be produced.
Relief of symptoms of CF for respiratory system?
medications to relax muscles in airways (bronchodilators)
antibiotics to fight infections
DNAase enzymes to break down DNA from WBCs
steroids to reduce inflammation in lungs
Or phsyio therapy to dislodge mucus from lungs
heart/lung transplant
Relief of symptoms of CF for reproductive system?
Fertility treatment: IVF
Relief of symptoms of CF for digestive system?
diet: high energy food, high protein, salt supplements
digestive enzymes supplements - to help digestion
Define gene therapy:
= inserting a new gene into the cell nucleus to replace a defective gene that causes a disorder
What vectors can you use for gene insertion in gene therapy?
Liposomes (eg spherical cationic phospholipid bilayers)
Viruses (eg retroviruses)
What are the steps involved in gene therapy using liposomes?
1) CFTR gene is inserted into plasmid using restriction enzyme and DNA ligase ➡️ recombinant DNA
2) plasmids are mixed with liposomes - the negatively charged DNA is attracted to positively charged head groups of phospholipids
3) liposome-DNA complex forms and fuses with cell membrane ➡️ DNA is brought into cell and moves into nucleus
(( 4) CFTR gene is transcribed, mRNA moves to RER and it is transcripted. Functional CFTR is produced and targeted to plasma membrane ))
What are the pros of gene therapy using liposomes?
Liposome-DNA complexes can be breathed in as an aerosol using a nebuliser (easier to administer)
Up to 25% restoration of CFTR function in lung epithelial cells - alleviation of symptoms
What are the cons of gene therapy using liposomes?
DNA not inserted into target cell DNA, effect does not last as the DNA isn’t replicated
Not all cells receive the liposome-DNA complex (due to TSM) ?
What are the pros of gene therapy using viruses?
Virus can be breathed in as an aerosol using a nebuliser (easy to administer)
DNA inserted into cells own DNA and thus replicated as cells divide (only some type of viruses this way)
➡️ more effective way to get CFTR gene into cells
What are the cons of gene therapy using viruses?
- inflammatory response (side effects of virus: headache, fever)
- insertion of DNA into cells’ DNA may destroy other genes
What are the steps of gene therapy using viruses?
1) take out DNA sequence that allows virus to replicate and insert CFTR gene (with promoter and other regulatory DNA sequences)
2) cells are infected with the virus; viral DNA with CFTR gene is incorporated into the cells DNA (or remains independent in the cell if other type of virus is used)
3) CFTR gene is transcribed and translated and functional CFTR protein is produced
What is somatic gene therapy?
= Gene therapy of normal body cells
Not all cells receive the healthy allele
Mutation still passed on to next generation
What is germ line therapy?
= gene therapy of cells that produce gametes (gametocytes)
During embryo development, the healthy allele is inserted- gametocytyes receive healthy allele so that gametes are healthy and mutation is not passed on
Potential abuse - people would use it to change skin colour, adult height (illegal in the U.K.), potential defects in embryo, offspring have no say in whether or not their genetic material is modified
Ethical for gene therapy?
Reduced suffering
Increase qualify and length of sufferers life
In theory could get rid of some genetic diseases
Can be used where conventional treatment has failed
The right to research of scientific community (doesn’t mean they have to use)
Ethical against gene therapy?
Slippery slope - changing traits about themselves such as skin colour
too much scientific uncertainty- Not sure yet of long term effects, could be apparent later
germ line - lack of consent of embryo, and violating rights of future generations
What is carrier testing?
Take samples of cheek cells and test DNA to see if it contains most common mutations in CFTR gene
(80-85% reliable sometimes false negatives with unknown mutations)
Explain IVF (and PGD)
Remove eggs from ovaries and fertilise with sperm in a test tube
A cell is removed from the resulting embryos at the 8-16 cell stage and their DNA is tested for mutations associated with CF
Choose embryo which does not carry faulty alleles
What is PGD?
Preimplantation genetic diagnostic
What is prenatal screening and the two different types?
To check if the foetus has CF:
Amniocentesis
chorionic villus sampling (CVS)
What is involved in cvs?
Chorionic villus sampling:
During 8-12 weeks pregnancy - sample of placental tissue, including cells of foetus, is removed through wall of abdomen or vagina
DNA is analysed
What is involved in amniocentesis?
During 14-16 weeks pregnancy - a needle is inserted into the amniotic fluid and cells that have fallen off the placenta and foetus are collected
DNA is analysed
Amniocentesis vs CVS
Amniocentesis is carried out later in pregnancy, CVS is earlier (better to have an early abortion?)
2-3 weeks to get results of amniocentesis, CVS results available next day
0.5-1% chance of miscarriage with amniocentesis, 1-2% in CVS
What is involved in newborn screening?
Heel prick test - blood sample 5-14 days after birth and DNA is analysed
What is an ethical framework?
= ethical guidelines that can be applied in order to make an ethical decision
What are the ethical frameworks it genetic screening?
Rights and duties - baby right to life/ parents duty of care/ parents right to comfortable life without strain
Utilitarianism (maximising amount of good in the world) - is it good to bring a suffering child into the world?/ is a suffering child not worthy of being born?/ abortions?
Autonomy - make decision for yourself/ conflict with father?/ selfish?/ what about the affect on the foetus?
Virtues - eg faith and hope ➡️ no faith/hope that the baby will have a good life; justice - not having the abortion/having the abortion
