Week 4 - Cell Signalling

Question 1

What are the four parts of an amino acid?

Answer 1

Carboxyl group, amino group, alpha carbon (between carboxyl and amino groups) and a side chain

Give protons to become COO-

Question 2

What bonds are the carboxyl and amino groups available for?

Answer 2

Hydrogen bonding

Question 3

What is a non polar amino acid and give examples

Answer 3

Repelled by water so involved in hydrophobic interactions e.g. interior of soluble proteins and outside surface of proteins associated with the middle of membranes

Alanine, glycine

Question 4

What is a polar amino acid and give examples

Answer 4

Unequal distribution of charge

Serine, threonine and tyrosine form hydrogen bond with -OH groups

Question 5

What is a acidic amino acid and give examples

Answer 5

-COOH groups in aspartic acid and glutamic acid

Question 6

What is a basic amino acid and give examples

Answer 6

-NH2 groups in lysine and arginine

Accept protons to become NH3+

Question 7

What is special about cysteine?

Answer 7

Has a sulphydryl group -SH

Can form a covalent cross-link S-S between two cysteines called a disulphide bridge to form a dimer called cystine

Question 8

What is special about proline?

Answer 8

Side chain and amino group form a rigid five member ring structure. Interrupts alpha helices in globular proteins

Question 9

What is primary structure?

Answer 9

The sequence of amino acids in the protein

Question 10

How do you name peptides?

Answer 10

With free amino - N terminus - valine become valyl

Amino is named first - A comes before C

With free carboxyl - C terminus - stays the same

Carboxyl is named second C comes after A

Question 11

What is secondary structure? Give examples

Answer 11

Local folding in the polypeptide chain

Alpha helix - 3.6 amino acids per turn
Right handed spira - non polar amino acids towards center and polar towards surface
Bulky side chains can interfere
Proline doesn't have a free amino group
Charged AAs can disrupt

Beta pleated sheets
Can be parallel or antiparallel

Question 12

What is tertiary structure?

Answer 12

Determines if a protein is globular or fibrous
Chaperones assist correct folding
S-S bonds, hydrophobic or hydrophilic interactions can stabilise

Question 13

What is quaternary structure?

Answer 13

More than one polypeptide

Sometimes have a prosthetic group such as haemoglobin

Question 14

Describe myoglobin

Answer 14

Present in heart and skeletal muscle
Reservoir and carrier of oxygen
Single polypeptide with 8 stretches of alpha-helices
Each is partially terminated by a proline to form kinks
Loops are stabilised with hydrogen and ionic bonds
Does not show cooperativity

Question 15

Describe haemoglobin

Answer 15

In RBCs
Transports oxygen from lungs to capillaries and H+ and CO2 in the other direction
Composed of 2 identical dimers - 2 alpha, 2 beta subunits
Can bind 4 oxygen molecules - 4 heme prosthetic groups - each has one iron that can bind oxygen
Tight binding between dimers in deoxygenated state
Some weak bonds between dimers break giving relaxed structure in oxygenated state

Question 16

Describe collagen

Answer 16

Long rigid structure of three polypeptides called alpha chains are wound around one another in a triple helix every three amino acids is glycine
Contains proline

Found in skin, connective tissue, blood vessels, sclera and cornea

Fibril forming - 1 tendon, 2 carTWOlage, 3 blood vessels, 4 rhymes with floor - basement membrane
Fibril associative
Other

Question 17

Describe elastin

Answer 17

Found in lungs, ligaments and arteries return to normal length when stretching is removed

Question 18

Describe enzymes

Answer 18

Protein catalysts

Increase chemical reaction time by 10^3 to 10^8

Question 19

What is a holoenzyme

Answer 19

An active enzyme including its non-protein component

Question 20

What is an apoenzyme?

Answer 20

An inactive enzyme without its non-protein component

Question 21

What are the types of non protein component?

Answer 21

Cofactor - metal

Coenzyme - organic

             - transiently associated - co-substrate
             - permanently bound     - prosthetic group

Question 22

How can an enzyme reaction velocity be affected

Answer 22

Temp - more chance for molecules to meet and not energy to overcome activation energy - too much and enzyme denatures

pH - extremes can denature proteins - some enzymes work at high or low pHs

Enzyme activity depends on substrate concentration

Question 23

What is feedback inhibition?

Answer 23

The first reaction unique to a pathway is catalysed by an allosteric enzyme regulated by the concentration of the end-product

Question 24

What is allosteric regulation?

Answer 24

Positive or negative effector molecules bind non-covalently to a non-active site - non competitive inhibition due to conformational change, altering the enzymes affinity to its substrate

Question 25

What is covalent modification?

Answer 25

Addition or removal of phosphate groups from certain residues in the enzyme. Kinases and phosphatases. Conformational change which activate or inhibit enzyme activity

Question 26

What is the adjustment of enzyme synthesis or degradation?

Answer 26

Increasing or decreasing enzyme production or destruction will change number of active sites available and hence overall enzyme activity. Takes hours or days. Insulin regulation of glucose metabolism is an example

Question 27

What are the four types of signalling

Answer 27

Endocrine - hormones through the blood from glands Paracrine - signals are released locally and affect neighbouring cells Autocrine - signal molecules affect the cell that produces them Neuronal - transmitted along axons to neighbouring and target cells

Question 28

Two types of receptor

Answer 28

Surface - large and hydrophilic signalling molecules Intracellular - small, hydrophobic diffuse across membrane - STEROID HORMONES - affect transcription

Question 29

What is signal transduction?

Answer 29

Binding of a ligand to an external receptor to bring about an internal response

Question 30

Describe GPCRs

Answer 30

Polypeptides which span the membrane 7 times When ligand binds, changes conformational shape and allows it to bind to the alpha subunit of the G-protein. This binding decreases the affinity for GDP and so GTP binds. This activates the alpha subunit and it dissociates from the other two, which activates them to allow them to activate other molecules. The alpha subunit activates a target protein and then hydrolyses GTP to GDP and dissociates from the target protein. Inactive alpha subunit associates with the other two subunits to reform the inactive G-protein. This prevents constant activation of the target protein. The target protein is often an enzyme which produced product- secondary messenger molecules which act on intracellular signalling proteins

Question 31

Explain the phospholipase C pathway

Answer 31

GPCR activates G-protein which activates phospholipase C. This produces DAG and IP3 which binds to calcium channels on the ER. The calcium and DAG then activate protein kinase C which phosphorylates target proteins

Question 32

Explain the Adenylyl Cyclase pathway

Answer 32

Adrenaline binds to GPCR. Alpha unit binds to adenylyl cyclase which catalyses the production of cyclic AMP. cAMP activates protein kinase A which activates glycogen phosphorylase which catalyses the breakdown of glycogen into glucose - fight or flight

Question 33

Explain receptor tyrosine kinase

Answer 33

Inactive RTK made up of two monomers | Binding of ligand brings monomers together - dimerisation.

Question 34

Explain Ras pathway

Answer 34

Ligand binds to RTK Adaptor molecule binds to activated RTK and activated Ras-activating protein Activates Ras Activates MAP kinase kinase kinase Activates MAP kinase kinase Activates MAP kinase Activates a number of possible mitogen activated proteins which control gene expression If on permanent causes uncontrolled cell proliferation

Question 35

Describe the phospholipid bilayer

Answer 35

cholesterol - fits in gaps between phospholipids to stiffen membranes glycolipids - carbohydrate facing out Phosphatidylcholine most common phospholipid - has choline attached to phosphate group Asymmetrical - some phospholipids face extracellular space and some inwards

Question 36

What are the three types of transporter

Answer 36

Uniport - carries one solute in one direction Symport - carries two solutes in the same direction Antiport - carries two solutes in different directions

Question 37

Types of association with plasma membrane

Answer 37

Transmembrane Peripheral - lipid linked or protein linked Integral - integrated into the membrane

Question 37

Types of association with plasma membrane

Answer 37

Transmembrane Peripheral - lipid linked or protein linked Integral - integrated into the membrane

Question 38

Types of association with plasma membrane

Answer 38

Transmembrane Peripheral - lipid linked or protein linked Integral - integrated into the membrane

Question 39

Types of association with plasma membrane

Answer 39

Transmembrane Peripheral - lipid linked or protein linked Integral - integrated into the membrane

Question 39

Types of association with plasma membrane

Answer 39

Transmembrane Peripheral - lipid linked or protein linked Integral - integrated into the membrane

Question 40

What is the electrochemical gradient?

Answer 40

The concentration gradient and the voltage gradient

Question 41

Describe the sodium potassium ATPase

Answer 41

Sodium binds to the pump Phosphorylates itself using ATP Triggers conformational change - sodium ejected out of cell Potassium binds The pump is dephosphorylated Pump returns to original conformation - K released into cell

Question 42

Sodium glucose symport

Answer 42

Passive transport of sodium provides energy for transport of glucose against concentration gradient Sodium at high concentration out of cell due to na/k pump

Question 43

What are ABCs

Answer 43

ATP-binding-cassettes Have to ATP-binding sites on the inside of the membrane and two transmembrane domains that form a passage for transported molecules Active transport of ions, drugs and xenobiotics (not usually found in the cell) Implicated in multidrug resistance - responsible for extruding chemotherapeutic drugs from cancer cells