Genes and Health

Lungs:

allow rapid gas exchange between the atmosphere and blood.

Air is drawn into the lungs via the Trachea due to low pressure in the lungs created by the ribs and diaphragm

The Trachea divides into two bronchi which carry air to and from each lung

In each lung there is a tree like systen of tubes ending in narrow tubes, bronchioles, attatched to tiny baloon like alveoli.

Alveoli are site of gas exchange

Mucus in tubes of gas exchange system. Produced by goblet cells and walls of airways.

any dust or debris that enter become trapped in mucus, and it becomes wafted away by hair like structures cilia that cover epithelial cells lining the tubes.

Mucus is drier than usual resulting in a sticky mucus layer that cilia find difficult to move

The sticky mucus has two major effects on health:

increases chances of lung infection and makes gas exchange less efficicent

microorganisms become trapped in musuc and can cause illness-Pathogens

mucus normally moved to the back of the throat where it is swallowed, acid in stomach kills most microorganisms that are swallowed

CF mucus is too sticky for the cilia to nmove, the musuc production still continues producing layers of thick mucus

low levels of O2 because it diffuses slowly through it and epithelial cells use more O2. Harmful bacteria thrive in anaerobic conditions.

White blood cells fighting infection in the mucus die and release DNA which makes it more stickier.

repeated infections eventually weaken the bodys ability to fight pathogens and cause damage to the structures of the gas exchange system

Substances that diffuse into or out a cell move down a concentration gradient.

larger orgnaism- more exchange has to take place

Surface area to volume ratio= dividing total surface area by volume

Features of gas exchange surfaces: (needs to be rapid, high demand)

• large surface area of alveoli
• numerous cappillaries around the alveoli
• thin walls of the alveoli and cappilaries meaning a short distance between the alveolar air and blood in the cappillaries
• steeo concentration gradient

Rate of diffusion dependant:- Ficks law

• Surface area- rate of diffusion is directly proportional to the surface area, as the surface area increases so does the rate of diffusion
• concentration gradient- directly proportional, the greater the concentration gradient, the faster the diffusion
• thickness of gas exchange surface- inversely proportional, thicker the surface the slower the diffusion

sticky mucis blocks the narrow arteries preventing ventilation of the alveoli .

Thus reducing the number of alveoli providing surface area for gas exhange

Blockages at the end of the airways, allowing air to pass breathing in but not

resulting in over inflation of the lungs which could damage the elasticity of the lungs

CF- find it hard to take part in physical exercise because their gas exchange system cannot deliver enough oxygen to their muscle cells. Needed for aerobic respirtation

CF- become short of breath but exercise is very benificial to them

Structure of an amino acid:

amine group NH2

carboxylic acid group COOH

Hydrogen H

All attached to a central carbon

All have different R residual group

Two amino acids joined in a condensation reaction to form a dipeptide.

A peptide bond forms between the subunits

this process is repeated to form a polypeptide chain

A protein is made up of one or more polypeptide chains

The sequence of amino acids in the polypeptide chain is the primary structure of a protein

(OH and H groups)

the chain of amino acids may twist to form an alpha helix

Hydorgen bonds form between the C=O of the carboxylic acid and the NH of the amine group stabilising the shape

Several chains link into a Beta pleated sheet

hydrogen bonds hold the chain parallel

within one protein molecule there are sections of both

Creates a three dimensional shape

the polypeptide chain bends and folds to form a 3D shape. chemical bonds and hydrophobic interactions between the R group maintains this final tertiary structure of the protein

an R group is polar when sharing electrons is not quite even

Polar R groups attract other polar molecules, they are hydrophilic (water attracting)

Non-polar groups are hydrophobic (water repelling). They are arrranges so they face inside the protein

• Ionic bonds between ionised R groups
• Hydrogen bonds
• disulphide bonds between R groups containing SH groups

A protein can be made from several polypeptide chains held together- Quaternary structure

Conjugated- they have another chemical group associated with their polypeptide chain

Globular protein:

• polypeptide chain is folded into a compact spherical shape. soluble due to hydrophilic side chains projecting out.
• important in metabolic reactions.
• enzymes are globular- their 3D shape is crucial to their ability to form enzyme-substrate complexes and to catalyse.
• antibodies

Fibrous protein:

• remain as long chains
• several polypeptide chains cross linked for additional strength (Hydrogen bonds)
• insoluable- important structureal molecules
• keratin, collagen, skin, tendons, bones, cartilige
• staggered strands avoiding creation of weak points

Two layers of phospholipid

two fatty acids; a negatively charged phosphate group replaces the third fatty acid

The phosphate head of the molecule is polar- one end is slightyly positive and the rest is slightly negative. making the head attract other polar molecules (hyrophilic)

The fatty acid tails are non-polar (hydrophobis)

Phospholipds arrage themselves to avoid contact between the between the tails and water. Forming a structure with their tails on the surface or in spherical clusters called micelles, or form a bialayer (favoured) because the two fatty acids are two bulky to fit in the interior of a michells.

Bialayer- no exposed hydrocarbon chains

cells are filled with watery aqueaus cytoplasm tissue fluid. The cell surafce membrame form their most stabe arangement.

cell surface membrane contains proteins, cholecterol:

• glycoproteins (proetin attached to a polysaccaride)
• glycolipids (protein attached to a polysaccaride)

some proteins span the membrane, other are found in the inner layer or only within the outer layer. membranes have hydrophobic areas posiotioned in the membrane

some proteins are fixed in the membrane but others are not and can move around the phospholipid bialyer.

Phosphate heads are more electron dense to show up darker and tails forming the lighter inner part of the sandwich:

two types of protein- those who can be dissociated easily by increasing the ionic strength and those that could only be removed by adding detergents supporting some proteins are loosely attached and some are embedded.

Freeze fracture electron studies- revealing a smooth mosaic surface interspersed by integral proteins

labelled molecules that attach to specific molecules- membranes are asymmetric, the outside surface of membrane is different to the inside

fusing mouse and human cells together, florescent label, after 40 mins as 37C there was a complete intermixing showing the proetins diffused through the membrane showing it was fluid

more phospholipids containing unsaturated fatty acids in membrane the more fluid it is. the Kinks in the hydrocarbon tails of Unsat phospholipids prevent packaging close-more movement

The net movement of molecules or ions from a region of their higher concentration to a region of their lower concentration. 

will continue until equilibrium when the substance is spead evenly throughout

small uncharged molecules diffuse down the concentration gradient

small molecules diffuse rapidly

Hydrophillic molecules are larger and cannot diffuse through the bialayer

They may diffuse through water filled pores in channel proteins than span the membrane

each channel protein has a specific shape only a particular ion can bind

some channels can be open or closed depending on the presence or absence of a signal/hormone or change in potential difference. these are gated channels

some are carrier proteins.

the ion or molecule binds to the specific site on the protein and the protein changes shape so an ion can cross the membrane. 

the movement can be in either direction dependant on the concentration difference

passive transport- no metabolic energy needed

net movement of water molecules from a solution with a lower concentration of solute to a solution with a higher conc of solute through a partially permable membrane

water molecules from hydrogen bonds with the solute reducing the movement of these water molecules. 

passive- no energy

Substances moving against a concentration gradient from low to high

energy required

specific carrier proteins are needed

the energy comes from respiration and supplied by energy transfer molecule ATP

The substance to be transported binds to a carrier protein

Energy from ATP changes the shape of the carrier protein causing the substance to be released in the other side of the membrane

Very large molecules need to be transported across a cell membrane. Bulk transport

Exocytosis- release of a substance usually proteins or polysaccharides from the cell as vesicles, fuse with the cell membrane (insulin)

Endocytosis- substances are taken into cell by creation of a vesicle 

part of the cell membrane engulfs the solid to be transported and then absorbed by endocytosis (cholesterol)

these cells produce musuc, which is continuosly regulated to maintain a constant stickyness of the mucus. Must be runny enough to be moved by the beating of cilia but not runny so it floods the airway

The regulation of of water content is through transport od Na and Cl ions across epithelial cells

water then follows ions because of osmosis

If the mucus contains too much water it is detected by the epithelial cells.

carrier proteins in the basal membrane actively pump Na ions out of the cells.

the concentration of Na in the cell falls setting up a concentration gradient across the apical membrane

Na diffuse down this gradient. the ions pass into the cell by facilitated diffusion through Na channels in the apical membrane

This raises the Na in the tissue fluid on the basal membrane creating a potential differnce between the tissue fluid and the nucis. The tissue fluid contains more positively charged ions than the mucus. This creates a electrical gradient. which causes negatively charged Cl ions to diffuse out the mucus into the tissue fluid via the gaps in the neighbouring cells

The elevated Na and Cl concentrations in the tissue fluid draw water out the cell by osmosis across the basal membrane into the tissue fluid. Solute conc in higher in the cell than mucus

water is drawn out the mucus through osmosis across the apical membrane into the cell

too little water, Cl ions are transported across the basal membrane into the epithelial cells. 

this creates a concentration gradient across the apical membrane. the CFTR protein channel is open.

Cl ions diffuse out of the cell through the CFTR channels down the concentration gradient into the mucus. when open it inhibits the NA ion channels to open

the build up of negatively charged Cl ions in the mucus creates an electrical gradient between the mucus and the fluid. Na ions diffuse out the tissue fluid and down this gradient.

this draws up water out the cell by osmosis until the solutions on wither side of the membrane have the same concentration of free water molecules - isotonic

preventing the mucus becoming too sticky

In CF the CFTR protein may be missing or not functioning correctly

too little water in the mucus Cl cannot be secreted across the apical membrane.

no blockage of the Na channels so they are always open, a continue of Na absorption by the epithelial cells.

raised level of Na draws chloride ions and water out the mucus into the cells.

making the mucus more viscous and harder for the cilia to move it so the mucus is not cleared out the lungs effectively.

sticky mucus builds up and becomes frequently infected with bacteria causing a spiral or airway inflammation and damage

Difficulty maintaining body mall because of problems with digestion and absorbtion of nutrients

High basal metabolic rates

Poor appetities but have to eat  more than most people and high-energy food.

need to take food supplements that contain digestive enzymes to help break down large food molecules

Chemical breakdown of food occurs in the small intestine

Glands secrete digestive enzymes into the lumen of gut where they act as catalysts to speed up the extracellular breakdown of food molecules

Some enzymes are produced in the exocrine glands outside the gut which secrete into the duct.

Pancreatic cells produce enzymes for the breakdown of proteins, carbohydrates and lipids, they are delivered to the gut in pancreatic juice through the pancreatic ducts

in CF, the pancreatic duct becomes blocked by sticky mucus impairing the release of digestive enzymes.

the lower concentration of enzymes within the small intestine reduces the rate of digestion, so food is not fully digested and nutrients not fully absorbed. 

A higher proportion of partially digested and undigested food means energy is lost in the feces- malabsorption syndrome

pancreatic enzymes become trapped behind the mucus blocking the pancreatic duct which damage the pancreas itself.

Hard, damaged, fibrosed tissue in the pancreas

damage occurs to the cells within the pancreas that produce hormone insulin which is involved in the control of blood sugar levels, diabetes can occur

Enzymes- globular proteins that are catalysts and speed up chemical reactions.

precise 3D shape with an active site made from amino acids

Lock and key theory:

molecule with a complementary shape fits onto the active site. These substrate molecules form temporary bonds with the amino acid on the active site to produce an enzyme-substrate complex

after the reaction the products are released leaving the enzyme unchanged

substrate is the key and the enzyme is the lock

each enzyme catalyses one specific reaction because only one shape of substrate will fit into its precisely shaped active site

Induced fit theory:

active site is flexible and when the substrate enters the active site the enzyme molecule changes shape slightly sitting more closel;y around the substrate. it will return to its original shape

Bonds must be broken to convert substrate to product.This requires energy

This is activation energy

Without an enzyme, temperature would provide this energy

The heat agitates atoms in the molecules, the molecules become unstable and the reaction proceeds.

Enzymes reduce the amount of energy needed to bring about this reaction

the active site and the complementary substrate are electically charges groups. the attraction of these distort the shape of the substrate and assist in breaking the bonds or making new bonds. The active sites may contain amino acids withi acidic side chains which are favourable for the reaction.

enzymes catalyse intracellular, extracellular.

catabolic- breaking down larger molecules into smaller ones

anabolic- builds up

Rate of reaction is measured by determining the quantity of substrate used or formed at a given time

initial rate of reaction is the slope of rapid phase of the reaction

the initial rate of reaction is directly proportional to the enzymes concentration because the more enzyme is oresent, the greater number of active sites are available to form enzyme-substrate complexes

the high substrate concentrations, the enzyme concentrations limit the rate of reaction

every active site is occupied and substrate molecules cannot enter an active site until one becomes free again 

Females have a reduced chance of becoming pregnant because a mucus plug develops in the cervix. This stops sperm from reaching the egg

Males commonly lack the vas deferens (sperm duct) on both sides which means the sperm cant leave the testes.

When the vas deferens are present it can become blocked by thick sticky mucus layers so fewer sperms are preset in each ejaculate