week 2 Flashcards
Lipid bilayer
Dynamic and selectively permeable
Contains membrane proteins enables signalling, communication and selective permeability
What do membrane proteins do
Signalling, communication and selective permeability
What do the fatty acids chains in membrane determine
Fluidity of membrane
What does amphipathic mean
Both hydrophobic and hydrophilic
Phospholipids are amphipathic
Intracellular signal transduction lipids
Rapidly generated/ destroyed by enzymes in response to a specific signal
Spatially and temporally generated - highly specific signal
Bind specifically to conserved regions found within many different proteins and once bound induce conformational and/or localisation and activity changes within these proteins
How does cholesterol alter properties of lipid bilayers
Cholesterol inserts between membrane phospholipids
This tightens packing in the bilayer/ membrane rigidity and decreases membrane permeability to small molecules
what does the fluidity of membranes allow
Signalling lipids and membrane proteins to rapidly diffuse in the lateral plane and interact with one another
Ensures membranes are equally shared between daughter cells following cell division
Allows membranes to fuse with other membranes e.g. exocytosis
Integral and peripheral membrane proteins
Single pass- integral
Multi pass transmembrane protein- integral : hydrophobic amino acids with side chains interacting with lipid mono layer
B-barrel- integral
Lipid-linked -peripheral
Peripheral membrane protein -peripheral
What are functions of membrane proteins
Transport
Enzymatic activity
Signal transduction
Cell-cell recognition
Intercellular joining- connecting neighbouring epithelial cells
Attachment to cytoskeleton and extracellular matrix ECM
Types of passive transport
Simple diffusion: no membrane proteins involved, driven by concentration gradients
Facilitated diffusion- membrane proteins involved, driven by concentration gradients
No energy input ATP required for either
What does the ability of a solute to cross membrane by simple diffusion depend on
Concentration gradient
Hydrophobicity/ charge
Size
Membranes highly impermeable to ions- hydrophobic molecules can pass through
What are the two classes of facilitated diffusion
Channels- discriminates mainly on size and charge
Uniporter carrier proteins- involves a binding site for solutes, highly specific, binding of molecule to specific site causes conformational change resulting in movement of molecule from inside to outside
Transport inorganic ions/ small molecules across the membrane passively along their concentration/electrochemical gradient
What are channel proteins
Membrane proteins that form hydrophilic pores through plasma membrane
Most are non-directional ion channels
Show some selectivity based on size and charge
Fast
Gated channels offer more control than a simple membrane pore
What’s an electrochemical gradient
Combines the concentration gradient and membrane potential
The force driving a charged solute across a membrane is the concentration gradient and membrane potential
Why do cells maintain electrochemical gradients
To drive transport across membranes
To maintain osmotic balance
Electrical forces must be balanced
Without active transport to maintain electrochemical gradients ions would flow down their gradients through leak channels disturbing osmotic balance which results in cell death
How do cells carry out active transport
ATP driven pumps (primary active transport)- couple the transport of a solute against its gradient to the hydrolysis of ATP
Coupled transporters (secondary active transport)- couple the transport of one solute with the gradient to another against gradient
Light driven pumps found in plants and bacteria not humans -couple the transport of a solute against its gradient to the input of energy from light
How do coupled transporters work
Move solutes against concentration/ electrochemical gradient by coupling transport to Na+ gradient created by Na+/K+ ATPase
Do not depend directly on the hydrolysis of ATP (secondary active transport)
Symport- same directions
Antiport- opposite directions
Couple the transport of one solute with the gradient to another against gradient
Cell cycle
G1 and G2 are gap phases between mitosis and DNA synthesis
In G1 cells monitor their intracellular and extracellular environment to determine if conditions are correct during interphase cells continue with transcription and grow in mass
What is the restriction point in cell cycle
During G1
Decides whether to go into the cell cycle
G0 normal state for most cells (quiescence) not going through cell cycle
No growth factors
G1/S checkpoint
Will stop cell cycle if DNA is damaged
What do cyclin dependent kinases Cdks do
Regulate cell cycle checkpoint transitions
Are themselves regulated by feedback
Activating molecules are cyclins, proteins that cyclically fluctuate in concentration in cell cycle
What is a kinase
An enzyme which activates/ deactivates a protein by phosphorylating them
How do different cyclin-Cdk complexes regulate entry into different phases of cell cycle
Cyclins accumulate during the G1 S and G2 phases of cell cycle
By the G2 checkpoint enough cyclin is available to form M-Cdk (maturation promoting factor) complexes which initiate mitosis
Later in mitosis M-Cdk switches itself off by initiating a process which leads to destruction of cyclin
Cdk persists in cell as inactive until it associates with new cyclin synthesised during interphase
Consequences of checkpoint failure
Proliferation of cells in absence of growth factors
Replication of damaged DNA
Segregation of incompletely replicated chromosomes
Division of cells with wrong number of chromosomes
What is metabolism
The chemical processes that occur within a living organism in order to maintain life
What do catabolic pathways do
Break down complex molecules into simple molecules and release energy
What do anabolic pathways do
Build complex molecules from simple molecules and require energy usually in form of ATP
Oxidation
Loss of electrons
Reduction
Gain of electrons
Functions of connective tissue
Structural support for body and organs
Tensile strength
Binding tissues together
Immune defence
Metabolism and energy storage
Cushioning
Elasticity
What’s a fibroblast cell
Main cell type in non-specialised connective tissue
Produce and maintain extracellular matrix ECM and ground substance
Spindle shaped cell
Cigar shaped nucleus
Activated myofibroblasts involved in wound healing»_space; fibrosis
Fixed connective tissue cells
Fibroblasts
Fibrocytes- inactive fibroblasts
Adipocytes- fat cells
Macrophages- phagocytic immune function derived from monocytes
Wandering connective tissue cells
Plasma cells- oval nucleus actively produces antibodies
Eosinophils- 2 lobe nuclei eosinophilic granules
Neutrophils- multilobed nuclei phagocytic functions
Lymphocytes- round nuclei with small cytoplasm
Mast cells- basophilic granules inflammatory reactions histamine production
What is ground substance
Transparent semi solid gel
Part of extracellular matrix
Amorphous
Fibres are embedded in ground substance
Glycosaminoglycan GAGs backbone, GAG often is hyaluronic acid
Contains glycoproteins and complex carbohydrates
Hydrophilic binds water
Makes it strong resists compressive forces
Provides volume to connective tissue
What are elastin fibres
Secreted as precursor tropoelastin polymerises to become elastin requires glycoprotein fibrillin scaffold
Found in skin, ears, arteries, lung, bladder
Allows stretch and recoil to maintain shape
What are collagen fibres
Main fibre type, high tensile strength, flexible but can break, formation is triple alpha helix, thicker than elastin, doesn’t branch
Types of collagen fibres
Type 1- bone, skin, tendons, ligaments
Type 2 - cartilage
Type 3- reticular fibres reticulin
Type 4- basement membrane
What are reticular fibres
Delicate and thin
Form the framework of organs/ glands and blood vessels
How do we classify different types of connective tissue
Density of tissue- loose vs dense
Arrangement of fibres- regular vs irregular
What is lamina propria
Loose connective tissue
Immediately underlying certain epithelia
Very thin CT layer
Ground substance and loosely arranged fibres
Allows blood vessels to serve epithelial tissues above
Good for diffusion
Good breeding ground for microbes
Usually has immune cells
What’s the difference between dense irregular connective tissue and dense regular connective tissue
Irregular connective tissue the fibres are randomly arranged so are strong and can withstand pressure from different directions
Regular connective tissue fibres are organised in parallel good tensile strength but only resists forces in one direction
what is adipose tissue
Also known as fat tissue, its a connective tissue that’s mainly composed of fat cells called adipocytes
There’s two types of adipose tissue - white and brown
White adipose tissue
Unilocular
Have a single large lipid droplet
Look empty in sections
Can stain with Oil red O/Sudan Red
Most common in adult
Main function is to store excess energy in the form of fatty molecules mainly triglycerides
Other functions are to insulate body, cushion vital organs, secrete hormones and biological factors
Brown adipose tissue
Multilocular
Have many smaller lipid droplets
Look empty in sections- lipid washed away
Most common in newborn
In adult found around kidney/adrenals
Rich in mitochondria
Rich in capillaries
Specialised for thermogenesis
What are adipocytes
Energy storing cells that contain large globules of fat known as lipid droplets surrounded by a structural network of fibres
What are some genetic mutations in connective tissue
Type 1 collagen- osteogenesis imperfecta - brittle bones/malformation
Type 2 collagen- chondrodysplasia- cartilage defects, joint abnormalities
Type 1, 3 or 5 collagen- Ehlers Danlos syndrome- fragile, extra elastic skin, hypermobility joints
Fibrillin- Marfan’s syndrome - affects tissues rich in elastic fibres- aorta skeletal defects- long digits and arms
What does pluripotent mean
Potential to become any cell type
Multipotent
Can be lots but not every cell type
What does unipotent
Specialised, only one cell type
What is oligopotent
Can make a few cell types
What are hematopoietic stem cells
HSCs give rise to all blood cells types via committed oligopotent progenitor cell intermediates
DNA binding domain
Binds to the DNA sequence
Activation domain
Interacts with RNA polymerase
What is connective tissue made up of
Fibres
Ground substance
Cells
The fibres and ground substance make up the extra cellular matrix
Connective tissue definition
Composed of cells and a significant amount of extra cellular matrix. Differ in their physical properties because of differences in the types of cells and the composition of the extracellular matrix. There are different classes of connective tissue
Provides structural and metabolic support for other tissues and organs
Ground substance definition
The ground substance is a viscous, clear substance and is highly hydrated
It’s composed of proteoglycans-highly hydrophilic molecules that trap water within the matrix
Fibres are embedded in an amorphous ground substance which is the component of connective tissue that occupies the space between the fibres and the cells
Loose connective tissue definition
One of the two subclasses of connective tissue
One of its roles is to support epithelial tissue
Works to hold organs in place and is made up of extracellular matrix and collagenous elastic and reticular fibres
Dense connective tissue definition
What makes up tendons and ligaments and consists of a higher density of collagen fibres
Contains fewer cells and less ground substance in comparison with loose connective tissue
Ehlers-Danlos syndrome
EDS is a heterogeneous group of connective tissue disorders. They are characterised by joint hyper mobility, skin hyperextensibility , and tissue fragility
It can result from mutations in genes for the structure and synthesis of collagen. There are many subtypes
Marfan syndrome
A disorder of the body’s connective tissues, a group of tissues that maintain the structure of the body and support internal organs and other tissues
Heritable, autosomal dominant, mutation in the gene for fibrillin
Characteristics: being tall, abnormally long and slender limbs, deformity of chest wall, fingers and toes (arachnodactyly), heart defects, lens dislocation
Gene defect leads to abnormal production of fibrillin resulting in parts of body being able to stretch abnormally when under stress
No cure. Genetic tests used for diagnosis
Function of glycolipids and glycoproteins
Glycolipids- allow recognition by other cells e.g. cells of the immune system
Glycoproteins- allow cell communication (cell signalling)
4 major phospholipids in the mammalian plasma membrane
Phosphatidylethanolamine
Phosphatidylserine
Phosphatidylcholine
Sphingomyelin
All have similar structure so are able to link together (only head group is different except for sphingomyelin)
Other 3 all have central glycerol molecule
Intracellular signal transduction lipids
Phosphatidylinositol
Diacylglycerol
Ceramide
Sphingosine-1-phosphate
Minor proportion of the (phospho)lipid content of intracellular membranes. Derived from lipids residing in the plasma membrane
Rapidly generated/ destroyed (to prevent continuous signals) by enzymes in response to a specific signal
Spatially and temporally ( at a specific space at a specific time) generated= highly specific signal
Bind specifically to conserved regions found within many different proteins and once bound, induce conformational and/or localisation and activity change within that protein in membrane helping to increase signal (drive increased transduction)
Uniporter carrier proteins
Glucose transporter Glut2 in gut epithelia
Highly selective- transported molecule bound to carrier
Relatively slow
ATP driven pumps
Move solutes against concentration/electrochemical gradient by expending energy
E.g Na+ K+ ATPase
Operates continuously to expel Na+ that enters cell through other carrier proteins and channels. Hydrolyses ATP to ADP both an enzyme and carrier protein, couples the export of Na+ to import of K+
1) 3 Na+ bind inside cell, pump hydrolyses ATP and is phosphorylated
2) Na+ dependent phosphorylation causes pump to undergo conformational change, Na+ transferred across membrane and released
3) 2 K+ bind outside cell and pump is dephosphorylated
4) K+ dependent dephosphorylation causes pump to return to its original conformation. K+ is transferred across membrane and released
Na+/ glucose symporter (gut epithelia)
Na+ electrochemical gradient used to drive movement of glucose against its gradient
[Na+] high in gut low in cell. [glucose] high in cell low in gut
Binding of Na+ and glucose is cooperative i.e.binding of glucose is dependent on Na+
Because [Na+] is much higher outside cell glucose is more likely to bind to symporter when its in initial state- allows for binding of extracellular molecules
As a result there’s an overall net flow of glucose against its concentration gradient and Na+ along concentration gradient into cell
Na+/Ca2+ antiporter
Important in cardiac muscle
Cardiac muscle cell contraction is triggered by a rise in intracellular [Ca2+]
Much higher concentration of Na+ and Ca2+ outside cell than inside
Therefore antiporter moves 3Na+ in cell along gradient for every 1 Ca2+ out against gradient
Antiporter rapidly reduces intracellular Ca2+ concentration which reduces strength of cardiac muscle contraction i.e. causes cardiac muscle relaxation
Main function of the cell cycle
Growth and development
