Metabolism Flashcards
How are amino acids joined together?
Two amino acids are joined via a CONDENSATION REACTION
Water is release; OH from carboxylic acid side and H from amine side
What are the main types of bonding?
- COVALENT
- Two atoms share electrons
- Strongest bonds in a protein
- Found in primary structure
- Disulphide bridges (between two cysteine side chains)
- HYDROGEN
- Bonding between a partially negative atom and H which is partially positive
- occue between atoms on different side chains, or between water molecules
- IONIC
- electrostatic forces of attraction between charged side chains
- can be quite strong bonds
- majority of charged groups are at the surface of a folded protein
- VAN DER WAALS
- weak electrostatic forces of attraction between two atoms
- induced due to dipoles
- large number of such interactions = change in protein
- HYDROPHOBIC INTERACTIONS
- major force in driving folding of proteins into correct conformation
- creates hydrophobic core and hydrophillic surface
What is the difference between an alpha-helix and a beta-pleated sheet?
ALPHA-HELIX
- projection of side chains from individual amino acids
- usually helices are right handed due to L-amino acids
- proline adds a kink to the helix
- NH group is lost => no hydrogen bond with C=O group
BETA-PLEAT
- NH and C=O groups are at right angles to the backbone
- strands may run anti-parallel or parallel
Explain the different structures of a protein
Protiens fold into a single conformation of lowest energy
Denaturants = urea (H-bonds) and 2-mercaptoethanol (disulphide bonds)
- linear sequence of amino acids (written from amino terminus to carboxyl terminus)
- either folding into an alpha-helix or beta-pleated sheet
- arrangement of secondary structure into compact globular structures (domains)
- only in some proteins; 3D structure of protein composed of several sub units
Explain the mechanism of the drug warfarin
Warfarin is an anticoagulant which inhibits the carboxylation reaction of glutamate
Glutamate is carboxylated (using vit-K) to form gamma-carboxyglutamate which is used for the blood clotting cascade and is critical for normal function as the calcium binding capability is increased.
What is the concept of free energy?
A reaction will only occur spontaneously is delta-G is negative i.e. the products have lower energy (disorder) than the reactants
How does ATP act as a carrier of free energy?
ATP has 3 phosphanhydride bonds which have a large negative delta-G when hydrolysed
Reactions which are energetically unfavourable are then COUPLED to a energetically favourable one = making the overall delta-G negative and the reaction proceeds
Explain how enzymes act as catalysts
Enzymes = speed up the rate of reaction by lowering the activation energy (substrate binds to active site of enzyme causing bonds to be strained; accept (H+ too)/donate electrons)
Enzymes cause the substrate to resemble the transition state (a geometric and electronic arrangement so a reaction can proceed)
Explain how lysozyme works
Component of tears and nasal secretions
Hydrolyses sugar molecules within bacterial cell walls causing bacteria to lyse and die
Hydrolyses alternating polysaccharide copolymers of N-acetly glucosmaine (NAG) and N-acetyl muramic acid (NAM) representing a polysaccharide unit
Cleaves at beta (1,4) glycosidic linkage connects C1 of NAM to C4 of NAG
Residues: Glu35 and Asp52 needed for catalysis
- Glu35 protonates oxygen in glycosidic bond (breaks bond between 2 sugars)
- Water is deprotanted by Glu35
- Asp52 stabilises charge
- OH- attacks remaining sugar by adding itself; returning both Glu and Asp to their original state
Explain how glucose-6-phosphatase works
Predominatly found in the liver
Releases glucose from glycogen (low blood glucose levels)
Deficiency in this enzyme: Von Gierke’s disease; low blood glucose levels, slow growth, large livers and short stature
What are the differences between the lock and key and induced fit models?
Lock and Key: shape of the substrate matches the shape of the active site - explains specificity
Induced Fit: substrate causes conformational change in enzyme to form active site, release of products causes original state to reform
Describe the effects of substrate concentration on enzyme controlled reactions
Substrate concentration reaches a saturation point once there arent any active sites available.
Describe the effects of temperature on enzyme controlled reactions
Each enzyme has an optimum temperature
Lower - low rate of reaction
Higher - enzyme denatured
Describe the effects of pH on enzyme controlled reactions
Each enzyme has an optimum pH; any variations cause denaturation; enzyme may become ionised or protonated.
Explain the role of NAD
NAD+ is a coenzyme and is required in dehydrogenation reactions
Readily accepts a hydrogen and 2 electrons
E.g. pyruvate => lactate (enz. lactate dehydrogenase)
generates NAD+ to regenerate pyruvate
Draw a sketch to show the three stages of cellular metabolism
What is glycolysis?
Glycolysis is an anaerobic process which occurs in the cytoplasm and converts glucose into two pyruvate molecules and releases 2 ATP molecules.
What are the stages in the first half of glycolysis i.e. producing 2 moles of glyceraldehyde-3-phosphate?
- glucose ►glucose-6-phosphate (enz. hexokinase; ATP => ADP)
- glucose-6-phosphate ► fructose-6-phosphate (enz. phosphoglucose isomerase)
- fructose-6-phospate ► fructose-1,6-bisphosphate (enz. phosphofructokinase; ATP => ADP)
- fructose-1,6-bisphosphate ► glyceraldehyde-3-phosphate + dihydroxyacetone phosphate (enz. aldolase)
- dihydroxyacetone phosphate ►glyceraldehyde-3-phosphate (enz. triose phosphate isomerase)
What is the second stage of glycolysis to produce ATP?
- glyceraldehyde-3- phosphate► 1,3-bisphosphoglycerate (enz. glyceraldehyde-3-phosphate dehydrogenase; NAD+ + Pi=> NADH)
- 1,3-bisphosphoglycerate ► 3-phosphoglycerate (enz. phosphoglycerate kinase; ADP => ATP)
- 3-phosphoglycerate ►2-phosphoglycerate (enz. phosphoglycerate mutase)
- 2-phosphoglycerate ►phosphoenolpyruvate (enz. enolase)
- phosphoenolpyruvate ►pyruvate (enz. pyruvate kinase; ADP => ATP)
Compare the amount of ATP generated from aerobic and anaerobic metabolism of glucose
Anaerobic = 2 ATP from glycolysis
Aerobic = 38 ATP because of the TCA cycle and Oxidative Phosphorylation
Describe the fate of pyruvate
- ALCOHOLIC FERMENTATION
- pyruvate ► acetaldehyde (enz. pyruvate decarboxylase; H+ => CO2)
- acetaldehyde ► ethanol (enz. alcohol dehydrogenase; NADH + H+ => NAD+) anaerobic, occurs in yeast
- GENERATION OF LACTATE
- pyruvate ► lactate (enz. lactate dehydrogenase; NADH + H+ => NAD+) anaerobic, occurs in mammalian muscles during intense activity
- GENERATION OF ACETYL COA
- pyruvate ► acetyl CoA + CO2 (enz. pyruvate dehydrogenase complex; NAD+ => NADH) occurs in mitochondria of cells acetyle CoA can be used to produce ATP
What are the reactions catalysed by lactate dehydrogenase?
Lactate Dehydrogenase - LDH
Present in; heart, liver, kidney, skeletal muscle, brain, lungs and blood cells.
Catalyses conversion of pyruvate to lactate and vice versa
High levels can be diagnostic of:
- stroke
- heart attack
- liver disease
- muscle injury
- muscular dystrophy
- pulmonary infarction
What are the reactions catalysed by creatine kinase?
Creatine kinase - CK
Used to convert creatine phosphate to create and ATP when there is a high demand for ATP
Muscle damage = CK leaks into the bloodstream
High levels:
- myocardial infarction
- extent of muscular disease
- cause of chest pain
- discover carriers of muscular dystrophy
Tests can measure total CK levels or a specific isoform
What does the pyruvate dehydrogenase complex consist of?
Consists of 3 enzymes and 5 co-factors.
Enzymes :
- pyruvate decarboxylase
- lipoamide reductase- transacetylase
- dihydrolipoyl dehydrogenase
Co-factors:
- thiamine pyrophosphate (PG 1) = loses a proton, so the carbocation produced attacks pyruvate
- lipoamide (PG 2) = undergoes oxidation and reduction
- FAD (PG 3) = can accept and donate 2 electrons with 2 protons
- NAD+
- CoA
Explain the oxidative decarboxylation reaction.
- Pyruvate is decarboxylated to hydroxyethyl TPP
- Oxidised and transfered to lipoamide to produce acetylipoamide
- Acetyl group is transfered to CoA to give acetyl CoA
- Lipoamide is regenerated
- Regeneration of FADH2 and NADH
How are fatty acids and amino acids converted to acetyl CoA?
AMINO ACIDS = undergo transamination to remove the amine group this forms a keto acid and
e.g. alanine + alpha-ketoglutarate => pyruvate + glumate (enz. alanine aminotransferase)
pyruvate - enters Krebs
glutamate - reconverted to alpha-ketoglutarate to generate NH4+
FATTY ACIDS ??
Recall the steps of the Krebs (TCA) Cycle
- oxaloacetate ► citrate (enz. citrate synthase; acetyl-CoA => HS-CoA +H+
- citrate ► isocitrate (enz. aconitase)
- isocitrate ► alpha-ketoglutarate (enz. isocitrate dehydrogenase; NAD+ => NADH + H+ + CO2
- alpha-ketoglutarate ► succinyl-CoA (enz. alpha-ketoglutarate dehydrogenase complex; HS-CoA NAD+ => NADH + H+ + CO2)
- succinyl-CoA ► succinate (enz. succinyl-CoA synthetase; GDP +Pi + H2O => GTP HS-CoA)
- succinate► fumarate (enz. succinate dehydrogenase; FAD => FADH2)
- fumerate ► malate (enz. fumerase; water)
- malate ► oxaloacetate (enz. malate dehydrogenase; NAD+ =>NADH + H+)
Each turn produces 2 CO2, 3 NADH, 1 GTP, 1 FADH2
Summarise the glycerol-phosphate shuttle
Carries electrons (from NADH produced during glycolysis) from the cytoplasm to the mitochondria in skeletal muscle and the brain and to regenerate NAD+
- dihydroxyacetone phosphate ► glycerol-3-phosphate (enz. cytoplasmic glycerol-3-phosphate dehydrogenase) TRANSFER OF ELECTRONS
- membrane-bound glycerol-3-phosphate dehydrogenase, transfers electrons to FAD => co-enzyme Q which is part of the ETC
Explain the malate-aspartate shuttle
Shuttle usually found in the heart or liver in order to regenerate NAD+
Net Reaction: cyto NADH + mito NAD+ ► cyto NAD+ + mito NADH
- oxaloacetate ► malate (enz. cytosolic malate dehydrogenase; H- from NADH)
MALATE ENTERS MITOCHONDRIA
- malate ► oxaloacetate (enz. mitochondrial malate dehydrogenase; NAD+ => NADH)
Malate can enter the mitochondria via a transporter (alpha-ketoglutarate transporter) exchanges malate for alpha-ketoglutarate.
This is produced via a transamination reaction:
glutamateAA + oxaloacetateKA => alpha-ketoglutarateKA + aspartateAA
Requiring another transporter (glutamate/aspartate) exchanging glutamate for aspartate
Name two examples where NADPH is used
NADH = catabolic reactions (breaking down)
NADPH = anabolic (building up)
NAD+ and NADP+ accepts 2 electrons and a proton (high energy- easily transferred) to produce NADH and NADPH respectively
- Thymidine synthesis:
- dihydrofolate ► tetrahydrofolate (NADPH + H+ => NADP+)
- Biosynthesis of cholestrol:
- 7-dehydrocholestrol ► cholestrol (NADPH + H+ => NADP+)
Draw a cross-section of a mitochondrion and label the parts
Outer membrane = limits size of the organelle
Inner membrane = folds inwards to form cristae
Intermembrane space
Matrix = contains soluble enzymes and molecules required for Krebs
Summarise the proposed evolutionary origin of mitochondria
Mitochondria established an endosymbiotic relationship with eukaryotes
Mitochondira only arise from pre-exiting mitochondria or chloroplasts
Mitochondria have their own genome (circular like prokaryotes, and non-histone associated)
Mitochondria have their own machinery to synthesise proteins
First AA is fMet (like in bacteria, rather than Met)
Some antibiotics prevent protein synthesis in mitochondria but not in eukaryotes
What is the chemiosmotic theory?
Chemiosmosis = the movement of ions across a partially permeable membrane, down their electrochemical gradient.
The chemiosmotic theory can be applied to oxidative phosphorylation:
- Protons are pumped from the matrix into the intermembrane space via the control of the electron transport chain
- Protons return to the matrix (down the electrochemical gradient) via ATP synthase which is an enzyme with a specific channel and can synthesis ATP
What are the major features of the electron transport chain?
3 Membrane Complexes:
- NADH dehydrogenase complex
- Cytochrome b-c1 complex
- Cytochrome oxidase complex
2 Mobile Carriers:
- Ubiquinone (co-enzyme Q)
- Cytochrome C
Each protein can accept electrons (and a proton)
How does the electron transport chain work?
- NADH is dehydrogenated via NADH dehydrogenase complex thus releasing NAD+, 2 electrons and a proton
- The electrons are passed to ubiquinone which becomes reduced to ubiquinol
- Electrons are passed to cytochrome b-c, and ubiquione forms again
- Electrons are passed to cytochrome C
- Electrons are passed to cytochrome oxidase complex
- Oxygen is the final electron acceptor which accepts a proton as well in order to produce water
order = NU-BCO
Whenever an electron passes through, a proton is pumped into the intermembrane space.
Each unit of the chain has a higher affinity than the previous unit
Electrons lose energy as they move from each complex
Explain the function of ubiquinone
A mobile carrier of electrons
Can either pick up one or two electrons to be passed to the cytochrome b-c complex
Has a hydrophobic tail which limits its movement to the lipid bilayer where it is needed
Explain the function of cytochrome oxidase
The final protein in the electron transport chain
Recieves 4 electrons from cytochrome C which are passed to O2 (high affinity for electrons) so that water can be generated.
4 protons are also pumped into the intermembrane space- enhances the proton gradient.
What is the general structure of ATP synthase?
Two distinct parts
- Membrane bound = F0
- a
- b
- c
- Projections into matrix = F1
- alpha
- beta
- gamma
Explain how ATP is synthesised using ATP synthase
- Protons flow through; causes the disk of the c subunit to rotate
- gamma subunit also rotates as it is fixed to the disk
- alpha & beta subunits are locked in a fixed position and do not rotate due to anchorage by the b and a subunits
gamma subunit = asymmetrical axle
beta subunit = undergoes structural changes due to rotation of gamma subunit; affinities for ATP and ADP alter. There are three conformations open, loose and tight
How is carbon monoxide poisonous?
CO binds to Fe2+ (in cytochrome oxidase) which blocks the flow of electrons
How is cyanide poisonous?
CN- binds to Fe2+ (in cytochrome oxidase) which blocks the flow of electrons
How is malonate poisonous?
Malonate acts as a competitive inhibitor with succinate for succinate dehydrogenase (allows FAD to pass on electrons)
Essentially, slows down the flow of electrons from succinate to ubiquinone
How is olgiomycin poisonous?
An antibiotic
Binds to the ‘stalk’ of ATP synthase and so the flow of protons is blocked preventing ATP synthesis and accumulating protons in the intermembrane space.
What types of fatty acids exist in the body?
May be saturated (straight chain) or unsaturated (C=C causes a kink in the chain)
How are fats derived?
There are three main sources from which fats are derived
- Diet ( release of bile salts which solublize fatty acid molecules - forms micelles which can be absorbed by enterocytes. Lack of bile salts = steatorrhea (fatty stool)
- De novo biosynthesis in the the liver
- Storage depots in adipocytes
How are fatty acids, such as palmitate, METABOLISED to produce acetyl-coA?
fatty acid ► acyl coA
- fatty acid + ATP + HS-CoA => fatty acyl CoA + AMP + PPi
- 2 phosphoanhydride bonds are broken (ATP>AMP)
- enz. acyl CoA sythetase
- Acyl CoA is generated on the outer mitochondrial membrane and is transported into the matrix using the CARNITINE SHUTTLE which involves a translocase
- carnitine ►acyl carnitine (enz. carnitine acyltransferase I; fatty acyl coA => coA) CYTOPLASM
- acyl carnitine ► carnitine (enz. carnitine acyltransferase II; coA => fatty acyl coA)
- The following reactions occur as part of the beta-oxidation cycle
- Oxidation
- fatty acyl-coA ► trans enoyl-coA (enz. acyl-coA dehydrogenase; FAD => FADH2)
- Hydration
- trans enoyl-coA ► 3-hydroxyacyl coA species (enz. 3-hydroxyacyl-coA hydrolase; water used up)
- Oxidation
- 3-hydroxyacyl coA species ► ketoacyl co A (3-hydroxyacyl-coA dehydrogenase; NAD+ => NADH)
- Thiolysis
- ketoacyl-coA ► acyl-coA species + acetyl coA (enz. beta-ketothiolase)
- acyl-coA species is shortened by 2 C in every cycle
- Oxidation
The beta-oxidation cycle continues till 2 acetyl coA are produced via thiolysis.
Palminate (16 C) requires 7 cycles and produces 129 ATP molecules.
How are fatty acids SYNTHESISED from acetyl coA?
Fatty acid biosynthesis = Lipogenesis
- acetyl coA ►malonyl coA (enz. acetyl coA carboxylase; ATP + HCO3- => ADP +Pi)
- malonyl coA ► malonyl ACP (enz. malonyl coA-ACP transferase; ACP => CoA-SH)
- acetyl coA ► acetyl ACP (enz. acetyl coA-ACP transferase; ACP => CoA-SH)
- CONDENSATION
- acetyl ACP + malonyl ACP ► beta-ketoacyl ACP (enz. beta-ketoacyl ACP synthase; release of CO2 and ACP)
- REDUCTION
- beta-ketoacyl ACP ► 3-hydroxyacyl ACP (enz. beta-ketoacyl ACP reductase; NADPH => NADP)
- DEHYDRATION
- 3-hydroxyacyl ACP ► trans enoyl ACP (enz. 3-hydroxyacyl-ACP dehydrase; release of water)
- REDUCTION
- trans enoyl ACP ► acyl ACP (enz. enoyl ACP reductase; NADPH => NADP)
Compare the synthesis and metabolism of fatty acids
SYNTHESIS
- Occurs in the cytoplasm
- ACP is a carrier
- Reduction occurs by using NADPH
- acyl + malonyl groups => fatty acid
METABOLISM
- Occurs in the mitochondrial matrix
- CoA is a carrier
- Reduction occurs using FAD/NAD+
- fatty acid => acyl + acetyl groups
What is medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD)?
autosomal recessive
patients should not go without food for more than 10-12 hours; stick to a high carbohydrate diet = body can not depend on fatty acids for energy
What is a primary carnitine deficiency?
autosomal recessive disorder
symptoms occur in infancy/ early childhood e.g. encephalopathies, cardiomyopathies, muscle weakness and hypoglycaemia
reduced ability of the carnitine transporter to take up carntine (needed for beta-oxidation) mutation in gene SLC22A5
How is cholestrol synthesised from acetyl-coA?
- 2 X acetyl coA ► acetoacetyl coA (enz. beta-ketothiolase; releases CoA)
- acetoacetyl coA + acetyl coA ► HMG-CoA (enz. HMG-CoA synthase; water used up, release of CoA)
- HMG-CoA ► mevalonate (enz. HMG-CoA reductase)
- enz. under negative feedback by cholestrol, mevalonate and bile salts
- mevalonate ► 3-isopentenyl pyrophosphate (IPP) (several phosphorylation and decarboxylation reactions)
- mevalonate > 5-phosphomevalonate (mevalonate kinase)
- 5-phosphomevalonate > 5-pyrophosphomevalonate (phospho mevalonate kinase)
- 5-pyrophosphomevalonate > mevalonate- 3-phospho-5-pyrophosphate (kinase)
- mevalonate-3-phospho-5-pyrophosphate > 3-isopentenyl pyrophosphate (phosphho mevalonate decarboxylase)
- IPP ►DPP (enz. isopentenyl pyrophosphate isomerase)
- DPP ► GPP (enz. geranyl transferase; uses IPP)
- GPP ► FPP (enz. geranyl transferase; uses IPP)
- FPP ► squalene (enz. squalene synthetase; FPP + NADPH => 2PPi + NADP+ + H+)
- squalene ►lanosterol
- squalene > squalene epoxide (squalene monoxygenase; NADPH + O2=> NADP +H2O)
- squalene epoxide > lanosterol ( squalene epoxide lanosterol cyclase)
- lanosterol ► cholestrol (reduced and demethylated; releases HCOOH and 2X CO2)
How are bile salts synthesised from cholestrol?
cholestrol ► glychocholate + taurocholate (bile salts)
bile salts = major breakdown products of cholestrol; generated in the liver and stored in the gall bladder
How are steroid hormones synthesised from cholestrol?
cholestrol ► pregnenolone (enz. desmolase)
Pregnenolone is the precursor to all classes of steroid hormones:
- glucocorticoids
- mineralcorticoids
- androgens
- oestrogens
- progestins
How is cholestrol transported round the body?
LIPOPROTEINS due to insoluble nature of cholestrol in aqueous solution
Composition of a lipoprotein:
- phospholipid monolayer with cholestrol
- apoproteins
- core: cholestrol esters and triacylglycerols
Cholestrol esters: synthesised from cholestrol and phosphatidylcholine (enz. LCAT). Allows more tight packaging due to hydrophobic nature
Lipoproteins can vary in their density depending on the amount of apoprotein, also allows recognition by different cell types.
How is cholestrol taken up into cells?
Mixed micelles are formed which consist of:
- free fatty acids
- bile salts
- cholestrol
- lysophosphatidic acid
- digestion of lipids by lipases produces MAG and DAG
Micelles are absorbed by enterocytes which line the small intestine; resynthesising TAGs into CM (chylomicrons) are produced and transported to the lymph and enter the blood stream at the thoracic duct or the left subclavian vein.
The enzyme lipoprotein lipase then catalyses the hydrolysis of triacylglycerols to glycerol (goes to liver for gluconeogenesis) and fatty acids (undergo beta-oxidation)
What are the differences between LDL and HDL?
LDL = low density lipoprotein - bad cholestrol
- transport new cholestrol synthesised from the liver to tissues
- continuous high levels of LDL = atherosclerosis
- larger in size and 40% is cholestrol esters
HDL = high density lipoprotein - good cholestrol
- transports cholestrol from tissues to the liver for use or disposal
- helps to lower total serum cholestrol
- smaller in size and 20% is cholestrol esters
What are the effects of mutations on the LDL receptor (LDLR)?
Cholestrol is only taken up by those cells which have the LDL receptor via receptor mediated endocytosis
Mutations in the LDLR can lead to familial hypercholesterolaemia (FH)
Inherited as a monogenic dominant trat
Heterozygous: higher cholestrol levels (2-3X) than normal people and susceptible to athersclerosis in middle age
Homozygous: severely high cholestrol approx 5X the normal level and atherosclerosis and myocardial infarction may occur in adolescence.
What mutations can occur in the LDLR which lead to FH?
- Deletion of LDLR gene = LDLR not synthesised
- Mutation throughout coding region = LDLR not transported properly from ER to Golgi
- Mutation in N-terminus = LDLR does not bind to LDL effectively
- Mutation in cytoplasmic domain = LDLR-LDL complex does not form correctly to lead to receptor mediated endocytosis
- Mutation in EGFP domain = LDL is not released from receptor in the endosome and LDLR is not recycled
What drugs can control hypercholesterolaemia?
HMG-CoA-Reductase Inhibitors (statins)
A competitive inhibitor of HMG-CoA reductase. Inhibits the production of mevalonate
Resins/ sequestrants
Binds to bile acid-cholestrol complexes to prevent their reabsorption by the intestine. Lowers LDL by 15-30% and raises HDL by 3-5%
What is endocytosis?
The entry of molecules into a cell via an endosome; they are either transported or become lysosomes so that its contents can be degraded.
What is exocytosis?
The movement of molecules out of a cell using vesicles
How is a protein secreted from a cell?
Secretory/exocytic pathway
- Nucleus to rough endoplasmic reticulum (RER)
- newly-synthesised proteins can enter the lumen of ER in order to undergo modifications
- folding
- formation of disulphide bridges
- glyosylation
- specific proteolytic cleavages
- assembly of multimeric proteins
- newly-synthesised proteins can enter the lumen of ER in order to undergo modifications
- RER to Golgi Apparatus
- travels in a vesicle via forward pathway
- moves from cis to medial and trans golgi network where the protein can undergo post-translational modification until the final form is reached
- sometimes protein reaches Golgi by accident and is returned to RER via return pathway
- Golgi Apparatus to Exocytosis
- proteins packaged into vesicles at trans Golgi network
- travels to plasma membrane where exocytosis occurs
What is constituitive secretion?
Exocytosis of vesicles occurs as soon as the protein is ready; usually unregulated and consists of plasma membrane proteins
How does regulated secretion occur?
Secretory vesicles are stored until a signal is received after which exocytosis occurs
The singnal may be chemical, hormonal or electrical
How does endocytosis occur?
- Early endosome
- endocytic material is taken up and may be recycled or degraded
- Late endosome
- endocytic material remains in this phase till maturity
- Lysosome
- can hydrolyse the endocytic material into simpler compounds
What are the three different types of endocytosis?
- Receptor mediated (e.g. LDL receptor with cholestrol)
- Pinocytosis (fluid)
- Phagocytosis (particles)
How are vesicles transported within cells?
Vesicles make use of the cytoskeleton directed by microtubules and actin filaments
formed in donor cell > fusion with donor cell > released > docked onto acceptor cell > fuses with acceptor cell > release of contents
Which disease are due to defects in the secretory/exocytosis pathway?
CYSTIC FIBROSIS
Mutation in CFTR gene; loss of phenylalanine residue preventing folding of protein and so is retained in RER
ROBINOW SYNDROME
Mutation in ROR2 which is responsible for cartilage and bone growth; retained and degraded in the RER causes dwarfism and dysmorphic facial appearance
What disease is caused by a defect in the endocytic pathway?
FAMILIAL HYPERCHOLESTEROLAEMIA
Mutation in the LDL receptor and so the cell can not take up LDL
