Cells, Components and Communication Flashcards
amino acid structure
Central Carbon with 4 groups attached:
- Amino group
- Carboxyl group
- Hydrogen group
- R group- side chain
physiological pH
7.4
what are amino acids dissociated into at 7.4 pH?
- Carboxyl group- carboxylate ion (negatively charged so acidic)
- Amino group is protonated by a hydrogen ion (positively charged so basic)
non polar amino acids
- Have side chains involved in hydrophobic interactions and tend to cluster in the centre of proteins
- Examples: glycine, alanine, valine, proline etc.
proline special structure
due to cyclic structure- disrupts secondary structure of proteins (eg. alpha helices, beta sheets), allows formation of fibres in collagen so is important in connective tissue
polar amino acids
- Side chains involved in hydrophilic interactions and tend to be found on surface of proteins
- Examples: serine, threonine, tyrosine, cysteine etc.
basic amino acids
- R groups accept protons at 7.4 pH
- Nitrogen in R groups
- Examples: lysine, histidine, arginine
acidic amino acids
- R groups are acidic at 7.4 pH so they have a negative charge
- Have carboxyl group in R gorup
- Examples: aspartic acid and glutamic acid
special case amino acids
Glycine- simplest amino acid, R group is just a hydrogen
Alanine- R group is a methyl group
Proline
Cysteine- sulfhydryl group allows for formation of disulphide bridges, important in quaternary structure of proteins
protein bonds
- peptide bonds form between amino acids between the carboxylate ion of one amino acid and the protonated amino group of the next
- strong covalent bonds, not affected by mild conditions like heat or ph
primary structure
sequence of amino acids, polypeptide chain
secondary structure
local folding in the polypeptide chain caused by interactions between atoms of the amino acids that aren’t involved in R groups
alpha helix
- Right-handed spiral of tightly packed coiled backbone of amino acids
- Amino acids with bulky side chains wont fit in the spiral eg. proline
- 3.6 amino acids per turn
- Found in keratin, myoglobin etc.
beta sheets
- parallel or antiparallel
Polypeptide chains line up next to each other and hydrogen bonds are formed between the opposing O- and NH+
tertiary structure
further folding assisted by chaperone proteins, determines whether protein is globular or fibrous, by the end of this process functional areas of the protein will be configured
quartenary structure
when proteins is made up for more than one polypeptide chain, sometimes with prosthetic group- inorganic group eg. haemoglobin
haemoglobin structure
- globular
- 4 polypeptide chains (2 alpha helices, 2 beta sheets)- each alpha group binds ot a beta group via strong hydrophobic bonds to form a dimer (2 dimers in a haemoglobin molecule), each dimer binds to the other via weak ionic and hydrogen bonds
states of haemoglobin
- Deoxyhaemoglobin (no oxygen)- tight binding between dimers
- Oxyhaemoglobin (oxygen-bound)- some weak bonds between dimer break, giving a relaxed structure
cooperatively of haemoglobin
If one of the 4 haemoglobins subunits bonds to oxygen, the others have increased affinity for oxygen. If one subunit releases oxygen, others have decreased affinity. Due to conformational changes in the protein structure.
myoglobin
- globular
- Found in skeletal and cardiac muscle
- One polypeptide- with many alpha helices that are partially terminated by prolines
- Oxygen carrier
- Does not show cooperativity- 1 unit
collagen general structure
- 3 alpha polypeptide chains that wind around eachother
- Important amino acids: glycine, proline
fibril forming collagen
- 1= skin, bone, tendon, blood vessels, cornea
- 2= cartilage, intervertebral discs
- 3= blood vessels
fibril associative collagen
bind to collagen fibres and link them to form ECM
- 9= cartilage
- 12= tendons
other types of collagen
- 4= basement membrane
- 7= underneath stratified squamous epithelia
elastin
- fibrous
- Synthesised from tropoelestin- secreted in ECM onto fibrillin scaffold
- Tropoelastin molecules crosslinked between lysine side chains
- Found in lungs, arteries
enzyme active sites
pocket containing amino acids that participate in substrate binding and catalysis i.e substrate binds, and product is released
apoenzyme
inactive enzyme without non protein component
holoenzyme
= active enzyme including non-protein component
cofactor
metal molecules that help enzymes to function
coenzymes
organic molecule that helps enzymes to function
cosubstrate
coenzymes that transiently (for a short time) associate with the enzyme
prosthetic group
coenzymes that are permanently associated with the enzyme
reaction velocity
number of substrate molecules converted to product/ unit of time
transition state
has the highest associated energy in any part of the reaction: to complete the reaction there must be sufficient energy to form this state, transition state is lowered in enzyme catalysed reactions
effect of substrate concentration on reaction velocity
Increased concentration of substrate increases the rate of reaction until all the active sites available are saturated and further increases have no effect
Effect of Temperature on Reaction Velocity
- Increase in temp= increased number of molecules have sufficient energy to reach transition state
- Velocity therefore increases but only until 37C, further increase will break weak bonds holding secondary and tertiary structure and denature enzyme so reaction velocity will decrease
Effect of pH on Reaction Velocity
- Optimum pH is specific for each enzyme and reflects its function
Eg. Pepsin’s optimum ph 2 is reflected in the acidic nature of the gastric lining where it helps with digestion - Extreme pH denatures enzymes
allosteric regulation
- Bind non covalently and non-competitively to allosteric site and can positively or negatively modulate the enzymes
- Causes conformational changes in the activity site, altering the affinity of the enzyme for its substrate or modifying maximum catalytic activity
feedback inhibition
allosteric enzyme is regulated by the concentration of the end product of the reaction pathway.
- Inhibition only when there is too much end product
- End product binds to allosteric site of enzyme that catalyses regular rate limiting step of series to change its conformation
- Reaction pathway carries on when there is no end product (or v little)
covalent modification
- Addition or removal of phosphate groups from specific serine, threonine or tyrosine residues in enzyme
- Either addition or removal can act as an activator or inhibitor depending on the specific situation
adjusting enzyme synthesis/degradation to regulate enzymes
- Usually affects enzymes that are active at a particular physiological or developmental stage
- Alters the number of active sites available and hence the overall enzyme activity
- Slow process that involves blocking of RNA
- Eg. Insulin regulation of glucose mechanism
signal transduction
binding of a ligand to an external receptor to bring about an internal cellular response
types of signalling
- Endocrine- hormones (ligands). Secreted from endocrine glands transported in blood and act on distant target cells
- Paracrine- paracrine factors (ligands) secreted and targets nearby cells over a short range
- Autocrine- ligands secreted that acts on the same cell eg. In immune cells
- Neuronal- electrical signals travel along the cell and neurotransmitters (ligands) are released through the synapse to the target cells
Membrane receptors- target receptors and mechanism
hydrophilic ligands as they are unable to cross the hydrophobic plasma membrane
Intracellular receptors- target molecules
small and hydrophobic eg. Steroid hormones (cortisol, testosterone ect.)
molecular switches
protein molecules that can either be activated (switching the pathway on) or inactivated by:
- GTP binding
- Phosphorylation
G protein coupled receptors (GPCRs) and similar receptors to it
proteins that span the membrane 7 times and are attached to G proteins, GTP acts on GPCRs
Similar receptors are steroid hormone receptors and enzyme coupled receptors
G proteins structure
usually made of 3 subunits (alpha, beta, gamma) but can be monomers, the alpha subunit binds to either GDP/GTP and has intrinsic GTPase activity
activation of GPCR
- Ligand binds to GCPR
- Alpha subunit separates from the rest of the G protein
- The activated alpha binds and activates the target enzyme
- This hydrolyses GTP to GDP so the alpha subunit dissociates from target enzyme and reassembles with the rest of G proteins
- Activated enzymes then act on downstream proteins
Adenynyl Cyclase (cAMP- dependant) Pathway
Ligand= variable but adrenaline is an example in the fight or flight response
1. Adrenaline binds to GPCR: GTP binds to alpha unit, activating it
2. Alpha unit binds to adenylyl cyclase (a membrane enzyme)
3. Adenylyl cyclase catalyses the production of cyclic AMP from ATP
4. Protein kinase A activates glycogen phosphorylase which catalyses the breakdown of glycogen to glucose
Glucose is imp for energy in a fight or flight response.
Phospholipase C pathway
- Ligand activates alpha unit of a G protein via GCPR
- Alpha subunit activates phospholipase C enzymes
- These enzymes catalyse the breakdown of inositol phospholipid (associated with the plasma membrane) into diagcylglycerol (DAG) (also membrane associated) and inositol-1,4,5-triphosphate (IP3)
- Calcium molecules move down the concentration gradient from the ER to the cytoplasm
- The DAG and the calcium molecules activate the protein kinase C which will phosphorylate target proteins
Receptor Tyrosine Kinase (RTK) Structure
Ligand= form of a dimer
Inactive RTK- made up of two monomers, intracellular components are tyrosine kinase domains and extracellular components are ligand binding domains
RTK Activation
- Binding of ligand dimer brings the two monomers together= dimerization
- Kinase activity is stimulated
- A tyrosine in the cytoplasmic portion of each monomer is phosphorylated by its partner
- Binding sites are created for intracellular signalling proteins that lead to the initiation of signal transduction pathways
RAS Pathway
- RTK activated by signal molecule
- Adaptor molecule binds to activated RTK and Ras activation protein
- Ras activated which then activates mitogen activated protein (MAP) kinase kinase kinase
- This phosphorylates MAP kinase kinase
- This phosphorylates MAP kinase
- This phosphorylates a number of possible mitogen activated proteins bringing about changes in protein activity and gene expression to facilitate cell proliferation
issue with Ras being permanently switched on
leads to uncontrolled cell proliferation- cancer
plasma membrane
- Selectively permeable barrier that separates and protects the interior of all eukaryotic cells from external environment
- Main components: phospholipids and proteins
- Phospholipid bilayer with embedded and associated proteins
endomembranes
plasma membranes that surround organelles inside the cell, have same basic components as plasma membrane, ratio of lipids to proteins in a membrane changes based on what the membrane encloses
lipids
- Most abundant macromolecule in membranes + plays structural and regulatory roles eg. IP3 and DAG from phospholipase C
- Have a hydrophilic head and two hydrophobic portions
- Lipids are amphiphilic and amphiphobic- have both hydrophobic and hydrophilic portions
glycolipid
- Hydrophilic head: glycerol-sugar molecule
* Hydrophobic tail: fatty acid, one with a kink cause by C=C double bond which increase membrane flexibility
phospholipid
- Hydrophilic head: phosphate-glycerol molecule
- Phosphatidylcholine (most imp phospholipid)- choline-phosphate glycerol molecule
- Hydrophobic tail: fatty acid, one with a kink cause by C=C double bond which increase membrane flexibility
sterol (eg. cholesterol)
- Hydrophilic head is attached to a planar steroid ring and a non-polar g=hydrocarbon tail
- Cholesterol fits into the gaps between the phospholipids of the membranes and stiffens the membrane
- The ratio of cholesterol to phospholipids in a membrane varies with the flexibility of the membrane- most cholesterol means stiffer membrane
types of transport proteins
- Uniport= carries one solute in one direction across membrane
- Symport= carries two solutes at the same time in the same direction across the membrane
- Antiport= carries two solutes at the same time in the opposite direction across the membrane
types of association with the membrane that transport proteins have
- Transmembrane (integral): high no. of amino acids in these proteins to associate in the hydrophobic bilayer
- Peripheral: can be monolayer associates, lipid linked or protein linked
simple diffusion across the membrane is done by which molecules?
- Small hydrophobic molecules- oxygen, CO2, nitrogen, benzene
- Small uncharged polar molecules- water, glycerol, ethanol
channel mediated passive transport
- Ions pass through the membrane via channel along a concentration gradient
- Channel provides a hydrophilic environment within the lipid bilayer
- Size of channel confers degree of selectivity onto a channel protein
transporter mediated passive transport
- Solute binds to specific binding site on transporter bringing about a conformational change
- Solute is transported and released
- Increasing solute concentration will increase rate of transport up to a threshold where rate will plateau as a result of a limited number of binding sites
transporter mediated active transport
- Active transport transports molecules again their electrochemical gradient- concentration gradient and voltage gradient ions move from an area of positive charge to negative
- Requires energy in the form of ATP or by coupling active transport with passive transport of molecules along concentration gradient (cotransport)
Sodium/Potassium ATPase process
- Sodium binds to pump
- Pump phosphorylates itself via ATP which triggers a conformation change in pump that causes Na+ to be ejected outside cell
- K+ bind
- The pump is dephosphorylated so it returns to original conformation and K+ is ejected inside cell
Sodium/ Glucose Symportprocess
- Passive transport of sodium= active transport of glucose, important in gut epithelial cells for food absorption
1. Passive transport of sodium provides energy for transport of glucose against concentration gradient
2. Sodium is constantly actively excreted by the Na/K ATPase to maintain higher concentration outside the cell
ATP Binding Cassettes
- 2 cytostolic ATP binding sites + 2 transmembrane transporter domains
- ABC hydrolyses ATP and induces a conformational change in the membrane spanning domain causing the transport of substrates
- Important in multidrug resistance- the transporter export ions, drugs and xenobiotics from cells- can include anti-cancer, anti-viral and immunosuppressive agents
Haem groups
Fe2+ oxygen binding sites
