Quiz 4 - Biosignaling, Carbohydrates Flashcards
6 Requirements for effective signal transduction
- Specificity
- Amplification
- Modularity - discrete components that interact
- Integration - Different signals combine to create response
- Feedback
- Fidelity - doesn’t decay over time and space
Autocrine
Signals bind to same cell
Paracrine
Signals bind to nearby cell
Synaptic
Involve signals crossing narrow synapse
Endocrine
Signals travel in bloodstream to distant targets
4 Components of Signal Transduction
- Signal
- Receptor
- Transduction Pathway
- Target
3 Types of signals
- Soluble - Proteins, amino acids, lipids, fatty acids, carbohydrates
- Linked - Integrins
- Physical - mechanical, light, temperature
G Protein-Coupled Receptors
External ligand binds to receptor, activates GTP binding protein that regulates another enzyme that creates intracellular second messengers
Receptor Tyrosine Kinase
Ligand binding activates TYR Kinase activity and autophosphorylation
Receptor Guanylyl Cyclase
Convert GTP to cGMP second messenger
Gated Ion Channel
Open or close in response to concentration of signal ligand or membrane potential
Adhesion receptor (integrin)
Interact with things out in the ECM and affect the cytoskeleton
Nuclear receptor
Hormones enter the nucleus through the membranes and bind to DNA
Dissociation Constant (Kd)
Measure of amount of bound ligand compared to free.
High affinity receptor requires little ligand to reach dissociation (low Kd)
Low affinity receptor requires more ligand to reach dissociation
4 roles of plasma membrane in signaling
- Receptor Localization
- Ligand Exposure
- Signaling Complex Formation
- Endocytosis
Protein Scaffold
Protein binds a series of signaling proteins together at the membrane to speed up signaling. Ex.) AKAP5 scaffold protein
Signaling Endosome
Small membrane bound endosomes that group signaling proteins
Lipid raft types and functions
- Calveolar - Calveolin creates a dip in the membrane
- Planar - level with rest of membrane
A. Signal promotion - groups signaling proteins together
B. Signal inhibition - separates proteins to prevent signaling
Endocytic Pathway
Sort internalized vesicles Vesicular Fusion and Excision Transport can occur between every compartment Rab GTPase proteins critical pH decreases along pathway
Endocytic pathway spatially and temporally regulates signaling
- Signal downregulation - endocytose and degrade or re-exocytose a receptor
- Signal maintenance - Increases concentration of receptor and ligand by reducing volume
- Signal generation - When downstream components of pathway are not membrane bound, endocytosis can bring signal to the enzymes
Signal transduction process
First messenger -> Receptor -> Signal Transducer -> Primary Effector -> Second Messenger -> Secondary Effector
How do chemical reactions transfer information?
- Complex formation or dissociation
- Structural change
- Post-translational modification
Post-Translational Modifications
Phosphorylation - kinase Ubiquitination - ubiquitin ligase Glycosylation Oxidation Methylation - methyl-transferase Acetylation - acetyltransferase SUMOylation
Mitogen-Activated Protein Kinase (MAPK) Signaling
Monomeric GTP-ase activates MAP Kinase kinase kinase > MAP kinase kinase > MAP kinase > downstream chain
Ex.) Insulin activating transcription
Janus Kinase (JAK-STAT) Signaling
Janus kinase dimer binds to a cytokine > STAT is phosphorylated > STAT enters nucleus and affects transcription
Phosphatidylinositol 3-Kinase (PI3K) Signaling
Growth factor binds to an RTK > PIP2 is phosphorylated to PIP3 > chain of proteins activated
Ex.) Insulin activating glycogen synthesis
Phospholipase C Signaling
Ligand binds to GPCR > alpha subunit of G-protein binds to Phospholipase C > PLC cleaves PIP 2 to create IP3 > IP3 binds to Ca2+ channels to affect other signal pathways
Ex.) Norepinephrine causing vasoconstriction
Targets are effected to change cell function
Nucleus - transcription, cell division
Actin/tubulin/filaments - cell structure and motility
Enzymes - initiate metabolic pathways
Receptors - alter signal transduction
Transporters - change intracellular environment
Ion channels - change membrane potential
Epinephrine pathway
Epinephrine binds to Beta-adrenergic receptor > G protein phosphorylated > alpha subunit activates Adenylyl cyclase > AC converts ATP to cAMP > Causes smooth muscle relaxation and vasodilation
Norepinephrine Pathway
Norepinephrine binds to alpha adrenergic receptor > G protein phosphorylated > alpha subunit activates Phospholipase C > PLC cleaves IP3 from PIP2 > IP3 opens Ca2+ channels > Ca2+ activates Calmodulin > Causes smooth muscle contraction and vasoconstriction
Insulin division pathway
Insulin binds to TYRK > TYRK phosphorylates IRS1 > IRS1 uses a chain of proteins to activate RAS (G protein) > RAS activates Raf-1 (MAP Kinase kinase kinase) > Raf activates MEK (MAP Kinase kinase) > MEK activates ERK (MAP Kinase) > ERK affects transcription factors
Insulin Glycogenesis pathway
Starts same as Insulin division > IRS activates PI3K > PI3K converts PIP2 to PIP3 > Factors activated to convert Glucose to glycogen
Toll-Like Receptors
Specific receptors recognize bacterial cell walls (Gram - or Gram +)
Monosaccharides
Single units of sugars. Can have 3-8 carbons
Glyceraldehyde
Monosaccharide. An aldotriose (3 carbons, =O on terminal carbon)
D-Glucose
Monosaccharide. An aldohexose (6 carbons, =O on terminal carbon)
D-fructose
Monosaccharide. A ketohexose (6 carbons, =O on 2nd carbon)
Constitutional isomers
Same atoms, but differ in attachment of atoms
Stereoisomers
Atoms are connected in the same order but differ in spatial arrangement
Enantiomers
Mirror image of a molecule
Diastereomers
Isomers that are not mirror images
Formation of cyclic sugars
Aldehyde sugars are highly reactive in linear form, form cyclic, form 6 carbon ring
Ketone sugars are less reactive, form 5 carbon ring
Pyranose
6 Carbon ring. Glucose forms 2 different conformations in solution. Form Chair and Boat conformations
Furanose
5 carbon ring. Fructose forms 2 different conformations in solution
Reducing Sugar
Able to reduce another molecule or element
Ex.) Cu2+ –> Cu+
Sugar is oxidized
Important indicator of blood glucose testing.
Reducing sugar has free aldehyde or ketone group. All monosaccharides are reducing sugars, glucose is more effective than fructose
Complex sugars
Glucose can be modified by acetylation, phosphorylation, etc.
Disaccharides
2 sugars joined together
Lactose = Galactose + Glucose 1-4 linkage
Sucrose = Glucose + Fructose 1-2 linkage
Polysaccharides
Chains of sugar monomers
Amylose
Chain of alpha 1-4 glucose links
Amylopectin
Branched chain of glucose attached to main branch by 1-6 link
Glycogen
Chain of amylose and amylopectin
Amylopectin branch chains maximum of 10 glucoses
Storage carbohydrate
Starch
Chain of amylose and amylopectin
Amylopectin branch chains maximum of 30 glucoses
Chitin
Monomer is N-acetyl glucosamine
Alpha 1-4 linkage
Structural carbohydrate (insect exoskeleton)
Cellulose
Beta 1-4 and 1-6 linkages
Requires cellulase enzyme to digest
N- and O- glycosylation
Carbohydrates bind to amino acids.
Bound to serine = O link
Bound to Asparagine = N link
Forms specific pattern of cell surface proteins on cell membranes involved in organ transplant rejection, immune response, etc.
Glycoconjugate purposes
Major component of ECM Filter substances in ECM Serves as lubricants between cells Bind to cations Regulate movement of molecules
Glycosidic bond
Aldehydes and Ketones react in alcohol to become hemiacetals or hemiketals, changing the chiral center. Substitution of a second alcohol produces an acetal or ketal via a glycosidic bond.
Glycosaminoglycans
Large polysaccharides with amines. Have negative charges (polyanionic) Hyaluronate Chondroitin Keraten sulfate Heparin
Hyaluronate
Found in connective, epithelial and neural tissues. Found in aqueous and vitreous humour.
Chondroitin
Major constituent of connective tissues. Lubricant of joints
Heparin
Made in liver, anticoagulant
Keratin Sulfate
Large, highly hydrated molecules in joints that absorb mechanical shock, contributes to glial scar formation
Mucins
Principle organic constituent of saliva, protects, lubricates, has antimicrobial effects