L6&7 - Harvesting Chemical Energy/Cell Communication Flashcards
Categories of fuel
- carbohydrate => broken down to simple sugar
- proteins => amino acids
- fats => simple fats
Glycolysis products
- 2 net ATP
- 2 NADH
- 2 pyruvate
Phosphofructokinase
Inhibited by: citrate, ATP
Stimulated by: AMP
Pyruvate oxidation products
- NO ATP
- 2 NADH (1 per pyruvate)
- 2 CO2 (by-product)
- Acetyl CoA (for citric acid cycle)
Kerbs/citric acid cycle products
- 2 ATP
- 6 NADH
- 2 FADH2
- 4 CO2
Kerbs cycle process
- CoA removed from Acetyl CoA
- 2 carbon chain attaches to an existing 4 carbon chain
- Chain partially broken down to produce CO2 (all carbon is used up by the end of the cycle)
- Electrons captured to reduce NAD+ to NADH
- ATP produced
- FAD reduced to FADH2
- Remaining 4 carbon chain attaches to new carbon from Acetyl CoA
Substrate phosphorylation
ATP generated by direct transfer of a phosphate group from a substrate to ADP
Oxidative phosphorylation
- ATP generated from oxidation of NADH and FADH2 and the subsequent transfer of electrons and pumping of protons
- ATP synthase enzyme catalyses but no substrate needed
Electron transport chain products
- 6 H2O
- high conc. Of H+ in intermembrane space
Chemiosis products
26 or 28 ATP
Diabetes mellitus
Impaired ability to produce or respond (unable to recognise) to hormone insulin (lack of functional insulin)
Result of diabetes (biological)
abnormal metabolism of carbohydrates and elevated levels of blood glucose ( ≥ 7 mmol/L fasting)
- no glucose in cells
- no ATP from glucose
- no glycogen stored for harder times
- altered volume and osmolarity of blood, with subsequent pathological consequences, due to built up blood glucose levels
Diabetes symptoms
- significantly increased hunger
- significant weight loss
Local signalling
Signal acts on nearby target cells
- paracrine (growth factors e.g fibroblast growth factor FGF1)
- synaptic (via neurotransmitters e.g acetylcholine Ach)
Long distance signalling
Signals act from a distance
- hormones
Stages of signalling
1) reception
2) transduction
3) response
Types of receptors
1) intracellular
2) membrane-bound / cell surface
- G protein couple receptor GPCR
- ligand gated ion channels
- receptor tyrosine kinase
GPCR structure
- Transmembrane proteins pass plasma membrane 7 times
- loops interact with molecules inside/outside cell
GPCR second messengers
- cAMP
- calcium ions and IP3 signalling
Ligand gated ion channels components
Receptor, ligand, ion channel, ion channel receptor/ionotropic receptor
Most common signal transduction pathways
Phosphorylation cascade
Signal transduction pathways
Signals relayed from receptors to target molecules via a cascade of molecular interactions
Components of typical phosphorylation cascade
Protein kinase (phosphorylate), phosphatase (dephosphorylate), serine/threonine (residues that are typically phosphorylated)
Time period of signalling
Proteins should only be activated as needed so signalling is for a short period of time to ensure homeostatic equilibrium
- All signals are for a limited time thus activation usually promotes the start of deactivation
- This means the cell is ready to respond again if required
Cellular responses
- Gene expression (start/stop): final effector is a transcription factor that activates gene expression in response to signalling by growth factor
- Alter cellular biochemistry occurring in the cell
- alteration of protein function to gain or lose an activity
- opening or closing of an ion channel
- alteration of cellular metabolism
- regulation of cellular organelles or organisation
- rearrangement/movement of cytoskeleton
- blood glucose: final effector may be a muscle enzyme that breaks down glycogen in response to epinephrine (adrenalin) signalling
Need for so many steps
- amplifies the response via multiple reactions (massive amplification)
- provides multiple control points
- allows for specificity of response (temporal/spatial control)
- allows for coordination with other signalling pathways
Deceived receptors
Viruses (surface spike glycoprotein (S protein) on coronavirus)
Anabolic reactions
Consume energy to build up from simple to complex molecules
- energy from ATP to complex molecule
Catabolic reactions
Release energy while breaking down complex molecules into simple molecules
- energy from complex molecule to ATP
Respiration equation
Carb. + oxygen = carbon dioxide + water + energy
Glycolysis location
Cytoplasm
Glycolysis process
- Glucose with 2 ATP splits in half
- NAD+ picks up H and electrons to make NADH
- ATP and pyruvic acid produced
Pyruvate oxidation location
Matrix of mitochondria
Pyruvate oxidation process
- CO2 produced from 3 carbon pyruvate to form 2 carbon chain
- Electrons stripped from 2 carbon chain to reduce NAD+ to NADH and H+
- Coenzyme A attaches to 2 carbon fragment to produce Acetyl CoA
Krebs/citric acid cycle location
Matrix of mitochondria
Intermediates of Krebs/citric acid cycle
Feed into other biochemical pathways
Series of reactions
Product of one reaction is the substrate for the next
ETC + chemiosis location
Proteins within inner membrane of mitochondria
ETC process
- NADH and FADH2 (from glycolysis and citric acid cycle) are oxidised to donate 1 or 2 electrons to a series of electron carriers in the transport chain
- Electrons transfer from protein to protein along the chain in a series of redox reactions
- at each transfer, each electrons gives up a small amount of energy
- this energy is used to pump H+ into the intermembrane space which establishes a proton gradient (storing energy as a proton-motive force)
- Oxygen “pulls” the electrons down the chain and is the final electron acceptor where it is reduced to water
Proteins in ETC
- 1,3,4 are transmembrane proteins
- 2 is a peripheral protein
Chemiosis process
- H+ in intermembrane space rush down concentration gradient through ATP synthase
- Turbine within ATP synthase is turned as a result
- Rotation of ATP synthase turbine enables phosphorylation of ADP to ATP
Homeostasis
Maintenance of relatively constant conditions within physiologically tolerable limits
Type 1 diabetes
- No insulin production due to destroyed beta cells often caused by autoimmune, genetic or environmental factors
- Affects 5-10% of diabetics (less common) and onset usually occurs in children/adolescents
- Requires insulin replacement
Type 2 diabetes
- Non-functional receptors (insulin resistance) despite insulin production
- Most (>90%) diabetics and are usually adults over age of 40
- Can be linked to other pathologies and obesity (but unsure how/why)
Importance of cell communication
need to be able to respond as an individual cell, and as part of a whole tissue
Signals
inside the body are often small molecules or chemical (but it can also be light - receptors in eyes, taste/smell - also chemical)
- these are what cells respond to
Ways of communication
- direct contact (via cell junctions - gap junctions or cell-cell recognition: diffusion of signalling molecules through cell-cell channels)
- secretion of signalling molecules (ligand) which are recognised by specific receptors in the plasma membrane of target cells
Cyanide in chemiosis
Blocks passage of electrons to O2 thus results in cell death
Specificity of receptors
Only target receptor on target cell interacts with ligands (shape determined function)
- allows exquisite control
Intracellular receptors
- primary messenger generally hydrophobic and small (can enter cell)
- least common method of signalling
Membrane-bound/cell surface receptors
- primary messenger generally hydrophilic and/or large
- most common method of signalling
GPCR function
Diverse: development, sensory reception (vision, taste, smell) etc.
Adenylyl/adenylate cyclase
Enzyme that converts ATP to cAMP which activates downstream protein
- pathway disrupted by cholera toxin
(can also be activated by things other than G proteins e.g Ca2+)
Phosphodiesterase
Breaks down cAMP (action blocked by caffeine)
Phospholipase C
Cleaves PIP2 into DAG and IP3 (both act as second messengers)
IP3
Second messenger that diffuses through cytosol and binds to gated channel in ER
Ca2+ action
Flows out of ER down concentration gradient and activate other proteins towards cellular response
Ligand gated channel example
Neurotransmission in nervous system
- released neurotransmitters bind as ligands which cause the ligand-gated ion channels to open in the postsynaptic membrane resulting in an influx of sodium ions and localised depolarisation
- electrical signal (action potentials) are propagated/transmitted to the next neuron in this way
Protein kinases
- Enzymes that phosphorylate (transfer a phosphate group from ATP to another specific protein)
- Typically this activates the protein
- A series of protein kinases in a row (with different names) each add a phosphate to the next kinase
Phosphatase
- Enzymes that dephosphorylate (remove the phosphate group from activated proteins)
- This renders the protein inactive, but recyclable/available for reuse
(While ligand is bound, the protein kinases can still be reactivated)
Serine / threonine
Amino acids/the residues that are typically phosphorylated
- DNA level mutations affecting these residues (causing them to become something else) will thus affect their
ability to be phosphorylated which could be detrimental
second messengers
small molecule that is not a protein and is involved at the beginning of the cascade
Normal blood glucose level
70-110 mg/dL (5 mmol/L)
Advantage of cell amplification
Individual signalling reaction (one ligand) can produce a large no. Products
GPCR signalling process
1) At rest:
- receptor unbound, G protein bound to GDP, enzyme inactive
2) Ligand binds:
- conformational change in receptor
3) G protein binds to receptor:
- GTP displaces GDP, G protein activated (while ligand bound), enzyme inactive
4) Activated G protein dissociates from receptor
- G protein binds to enzyme, enzyme activated
G protein inactivation
GTPase activity in G protein (hydrolysis of GTP to GDP and P) promoting G protein to release from enzyme and revert back to resting state
Ca2+ background info
high conc. outside cell, lumen of ER and matrix of mitochondria
- maintenance of conc. via calcium pumps needed as Ca2+ toxic to cells
- also means cell response strongly to Ca2+ = powerful signalling
Ligand gated ion channel/receptor process
ligand binds - elicit shape change - gate opens - specific ions flow into cell - ligand dissociates - gate closes - back to resting
