Topic 2- Genes and Health

formation of a peptide bond

formation of a peptide bond

condensation reactions occur between amine groups on one amino acid and carboxyl groups on other amino acids. a molecule of water is lost for the formation of each peptide bond.

primary structure

the specific sequence of amino acids in a polypeptide.

formed by condensation reactions

involves formation of peptide bonds

secondary structure

interactions of amino acids in polypeptide chains to form α-helices or β-pleated sheets.

involves the formation of hydrogen bonds (between C=O and N-H groups in different amino acids)

tertiary structure

further folding of the secondary structure into a precise/specific 3D shape.

involves hydrogen bonding, ionic bonding, and formation of disulphide bridges between R groups

quaternary structure

3-dimensional arrangment involving more than one polypeptide chain.

involves hydrogen bonding, ionic bonding, and formation of disulphide bridges between R groups

the importance of primary structure

the sequence of amino acids in a protein determine the position of R groups, which are responsible for hydrogen, disulfide, and ionic bonding present in the polypeptide chain. the bonds determine the folding and shape of the protein, which gives rise to specific properties that allow is to carry out specific functions

conjugated proteins

• proteins with a non-protein group associated with their polypeptide chain

• e.g. glycoproteins, lipoproteins, haemoglobin

fibrous protiens

• polypeptide chains remain elongated

• little or no tertiary structure

• repetitive sequences of amino acids

• hydrophobic R groups on the outside- insoluble

• has structural roles in organisms e.g. collagen, fibrin, keratin

globular proteins

• polypeptide chains folded into a spherical shape

• tertiary structure and some have quaternary structure

• does not have repetitive sequences

• hydrophillic R groups on the inside- soluble

• important metabollic roles, e.g. enzymes, thrombin, fibrinogen and prothrombin, haemoglobin

haemoglobin

• globular and conjugated

• contains haem (iron containing) groups

• 4 polypeptide chains

• has tertiary and quaternary structure

• soluble due to hydrophillic R groups on the outside

• required for binding and transport of oxygen in red blood cells

collagen

• fibrous

• 3 polypeptide chains

• has quaternary structure

• insoluble due to hydrophobic R groups on the outside

• provide structural strength and support in skin, artery walls

fluid mosaic model definition

described and fluid because the phospholipid tails move slightly and proteins are described to move through the sea of phospholipids

described as mosaic because of the random assortment of proteins, phospholipids, cholestrol- different shapes and sizes within the membrane

the fluidity of membranes allow them to fuse together- determined by the phospolipids; unsaturated fatty acids that make up phospholipids have kinks that disrupt the close packing to allow for more movement and therefore more fluidity

cell membrane structures and their functions

• glycolipids- act as receptors and stabilise membrane structure

• (extrinsic/peripheral) or (intrinsic/transmembrane) proteins- sit on top of the bilayer or completely span it, and can have a role in cell signalling pathways and stabilising membrane structure

• glycoproteins- role in cellular recognition and the immune response, act as receptors for hormones and neurotransmitters

• phospholipids- form the bilayer

• channel proteins- span the bilayer and control movement of molecules in and out of the cell

• cholestrol- disturbs the close packing of the phospholipids to regulate membrane fluidity- essential for membrane stability

Gorter and Grendel

red blood cell membranes contain enough phospholipids to cover the cell twice- the cell membrane is a phospholipid bilayer

Davidson and Danielli

electron microscope showed more detailed images of the cell membrane- darker outer layers (protein) and lighter inner layers (lipid) could be seen

freeze fracture

freeze fracture showed ‘bumps’ in the middle of the cell membrane- proteins are found embedded in the bilayer

Frye and Edinin

the proteins of two different cells were labelled with flourescent markers and fused, and the colours were seen to mix- the membrane is fluid as it allows proteins to move

Unwin and Henderson

some proteins release from the membrane easily by increasing ionic strength whereas others require strong detergents- intrinsic/integral proteins are fully embedded within the membrane whereas extrinsic/peripheral proteins are only loosely associated with the membrane

lectins

lectins (that only bind to carbohydrates) only bound to the outside of the cell membrane- carbohydrate is only found on the outside/tissue fluid side of the cell membrane

diffusion

the net movement of molecules down a concentration gradient- region of high to low

continues until equilibrium is reached

is passive

facilitated diffusion

passive movement of larger molecules down a concentration gradient via channel/carrier proteins

movement can be either direction

osmosis

the net movement of water molecules from a solution of low solute concentration to a solution of high solute concentration through a partially permeable membrane

active transport

movement of molecules across a membrane against a concentration gradient, usually using energy from ATP to drive pumps (eg carrier proteins) in the membrane

is active

one way direction

exocytosis

active bulk transport out of a cell: membrane bound vesicle containing substance fuses with the cell membrane and releases its contents- relies on the fluid nature of the membrane

endocytosis

active bulk transport into a cell: the cell membrane invaginates (bulges inwards) to form a vesicle that pinches off whilst enclosing the substance inside- relies on the fluid nature of the membrane

factors that affect rate of diffusion

• temperature- increasing temperature increases kinetic energy and therefore rate of successful collisions, so rate of diffusion increases

• concentration gradient- steeper concentration gradient increases rate of diffusion due to accumulation of molecules on one side

• stirring movement- increases kinetic energy

• surface area- larger surface area increases rate of diffusion

• distance thickness- shorter diffusion pathways will increase rate of diffusion

• size of molecule- smaller molecules diffuse faster as they have more kinetic energy

facilitated diffusion: carrier proteins

molecule or ion binds to specific site on the protein, which then changes shape as the molecule crosses the membrane

active transport: carrier proteins

substance binds to the carrier protein. ATP changes the shape of the carrier protein causing the substance to be released on the other side of the membrane

facilitated diffusion: channel proteins

they are specific to the molecule or ion that needs to be transported. gated channel proteins can be open or closed depending on the presence of a signal

mononucleotide structure

the pentose sugar is deoxyribose

organic base can be adenine, guanine, cytosine, and thyamine

DNA structure

DNA nucleotides are joined by phosphodiester bonds in condensation reactions to form two polynucleotide chains- the two DNA strands that twist around each other to form double helix. the strands are held together by hydrogen bonds between bases. the sugar and the phosphate group form the ‘sugar-phosphate backbone’ with the hydrophillic phosphate groups on the outside.

DNA replication

when a DNA molecule copies itself to make two identical new DNA molecules in order to pass down genetic information from cell to cell

DNA polymerase

acts as an enzyme to join adjacent mononucleotides with phosphodiester bonds, in condensation reactions to form the new DNA strand

compare and contrast structures of DNA and RNA

similarities:

• both made of nueclotides with structure of phosphate, pentose sugar, and organic base

• both contain adenine, guanine, and cytosine

• mononucleotides joined by phosphodiester bonds

differences:

• DNA contains deoxyribose sugar whereas RNA contains ribose sugar

• RNA contains uracil whereas DNA contains thyamine

• RNA is single stranded whereas DNA is double stranded

gene

a sequence of bases on a DNA molecule that codes for a specific sequence of amino acids in a polypeptide chain

how do mutations arise

mutations can arise due to errors in the process of DNA replication which happen randomly. risk of mutations can be increased by exposure to ionising radiation or carcinogenic chemicals

substitution mutations

base is substituted for another- changes one triplet in DNA

addition mutation

bases added into the DNA- usually causes a frameshift that changes all subsequent triplets

deletion mutation

bases in DNA deleted- usually causes a frameshift that changes all subsequent triplets

types of mutations that can result in the cystic fibrosis gene

• addition or deletion- frameshift changes the amino acid sequence, and CFTR protein may not be made especially if the mutation is at the start of the gene

• substitution- change in one codon may cause a specific amino acid to be missing and the CFTR protein may not fold correctly and its shape/structure may change, or it may change due to a shorter polypeptide chain if the mutation creates a stop codon

• substitution may not change it due to the degenerate nature of the genetic code, the changed codon may still code for the same amino acid

germ line mutations vs somatic mutations

germ line mutations occur in replicating DNA of ovaries or testes in the creation of gametes whereas somatic is in body cells after conception

germ line mutations are passed onto offspring whereas somatic are not

information about the CFTR protein

channel protein in the apical membrane of mucus producing (epithelial) cells of respiratory, digestive, and reproductive systems

its responsible for transporting chloride ions Cl- through cell membranes

cause of cystic fibrosis

• mutation results in change of the tertiary structure of a CFTR protein to make it faulty

• faulty CFTR protein cannot transport chloride ions so cannot move out of epithelial cells to enter mucus

• sodium ions do not move out of cells into the mucus and watter cannot move out of cells into mucus by osmosis

• mucus becomes sticker, thicker, and more viscous than normal, blocking parts of the body and impairing the function of certain systems

mucus: people without CF vs people with CF

without: the water in the mucus is regulated to maintain a constant viscosity, as it must be runny enough to be moved by beating cillia but not flood the airway

with CF: CFTR protein does not work properly and mucus becomes stickier than normal

regulation of water

water content is regulated by movement of sodium ions and chloride ions across the epithelial cells in the airways, where water follows the ions due to osmosis

effect of CF on digestion and absorption of digested food

thick mucus blocks the pancreatic duct

pancreatic digestive enzymes cannot leave the panreas and enter the small intestine- lower concentration of enzymes causes less efficient digestion and less products are absrobed into the blood

lack of glucose for respiration results in a lack of energy for cell activity causing tiredness

effect of CF on pancreas function

sticky mucus blocks the pancreatic duct so pancreatic enzymes are trapped behind the mucus and damage the pancreas to cause cysts of hard fibrous tissue

if cells that produce insulin are damaged it can result in diabetes

effect of CF on the male reproductive system

thick mucus blocks sperm ducts as sperm cannot leave the testes, decreasing chance of sperm fertilising an egg

effect of CF on femal reproductive system

thick mucus forms a mucus plug which blocks the cervix and prevents sperm from reaching the ovum in the oviduct to reduce chances of fertilisation

fick’s law of diffusion

role of mucus in the lungs

traps dust, debris, and microorganisms

cillia in the epithelial cells of the trachea and bronchi remove mucus by a wave-like beating, which is then coughed up or removed or swallowed, where the acid in the stomach destroys pathogens

adaptation of the mammilian lung for gas exchange

• many alveoli- larger surface area for gas exchange

• thin alveoli walls, one cell- short diffusion distance

• capillary walls are thin, one cell- short diffusion distance

• ventilation of alveoli- maintains steep concentration gradient

• blood flow in capillaries- maintains steep concentration gradient

effect of CF on the respiratory system

thick mucus cannot be removed by cilia, which remains in the lungs and blocks the bronchioles, restricting airflow and prevents ventilation of the alveoli. this reduces the number of alveoli involved in gas exchange, reducing the surface area and concentration gradient for gaseous exchange

blockages can also cause over-inflation of the alveoli and damage the elasticity of the lungs

reduction in gas exchange reduces oxygen supply to cells and tissues- during exercise muscle cells recieve less oxygen

lung infections

mucus build up in the lungs allows rapid multiplication of anaerobic bacteria due to the lack of oxygen in the mucus, causing a lung infection

white blood cells die and break down to release DNA which makes the mucus even stickier

repeated infections damage the lung tissue

enzymes

biological catalyst- produced by organism to speed up rate of biological reaction by reducing the activation energy

mechanism of en enzyme

1. the substrate fits into and binds to the enzyme active site

2. the shape of the active site fits the shape of the substrate

3. an enzyme-substrate complex forms and reaction occurs- the activation energy is owered as the substrate is held in the correct position

4. product is released from the active site and enzyme is unchanged

enzyme specificity

• enzyme has specific tertiary structure

• due to shape of active site

• only substrate will fit- lock and key theory

• forms enzyme-substrate complex

types of enzymes

intracellular enzymes catalyse reactions inside cells

exracellular enzymes catalyse reactions outside of cells

homolohous chromosomes

every human cell nucleus has 22 pairs +1 pair of sex chromosomes

in each pair, one from mother one from father

homologous chromosomes are the same length, same position of centromeres, and genes in the same position

punnet squares

illustrate all the possible ways in which two types of allele can combine to show all the genotypes

pedigree diagrams 

show family inheritence

genetic screening- screening to confirm diagnosis

blood sample taken (WBCs or cheek cells)

DNA tested for presence of defective gene to confirm diagnosis

• disadvantages include emotional stress of genetic abnormalities, flase positives or negatives, screening does not test for all possible mutations

genetic screening- pre-conception screening to identify carriers

blood sample or cheek cells taken, DNA tested for presence of defective gene

• disadvantages- same as testing for disorder

• advantages- couples can make informed decision about having children, can have IVF and embryos screened

genetic screening- pre-implantation genetic diagnosis

8 cell embryos have one cell tested for presence of defetive gene and only unaffected ones are implanted into the uterus

• disadvantages- false negative means parents could still have child with disorder, IVF is expensive, low success rates

• advantages- affected embryos not implanted, disease not passed on, avoids need for prenatal testing, miscarriage, or abortion

amniocentesis

• when fetus is in uterus, 15-17 weeks

• foetal cells collected from amniotic fluid surrounding the fetus using a needle to the abdomen

• DNA is extracted and analysed to detect defective gene

• implications: risk of miscarriage, false positive could result in abortion of healthy foetus, stress

chrionic villus sampling

• when the fetus is in uterus, 8-12 weeks

• fetal cels collected from the placenta using needle to abdomen or vagina

• disadvantages- false positive, stress, risk of misscariage

non-invasive prenatal diagnosis

• when fetus is in the uterus, 7-9 weeks

• analyses cell free detal DNA from mothers blood plasma

• DNA is extracted and analysed to detect defective gene mutation

• disadvantages- false postives, stress

social and ethical issues related to genetic screening

• fetus is living, abortion is murder

• who ha the right to decide if tests should be performed, implications of medical costs, disagreements over next steps

• abnormalities found may result in discrimination by employers or insurance

• fetus has right to live

• issues with confidentiality of parents and child

• risks of prenatal tests are not fully understood- risk of miscarriage