Biochemistry of Cell Communication Flashcards
1
Q
Hormonal Signalling
A
- Hormonal signalling molecules act to control metabolism in local or distant tissues
- ## Tends to be organised into cascades to control many metabolic processes
1
Q
Cell Signalling
A
- Metabolism requires signalling molecules => Ligands
2
Q
Peptide/Protein Signalling
A
- Peptides/proteins form the largest group of signalling molecules and involved in many systems
- Proteins can’t cross cell membranes so bind to receptors at the membranes
- Proteolytic cleavage allows specialised cells store inactive protein that can be cleaved to quickly respond to change and alter metabolism
3
Q
Steroids (Signalling Molecule)
A
- Present in most eukaryotes
- Synthesised from cholesterol
- Diffuse directly through the cell membrane
- Their receptors are either cytosolic or nuclear.
4
Q
Fatty Acids
A
- From hydrolysis of membrane fatty acids
- short half-life leading to very short acting molecules
- bind to GPCRs
- Roles in inflammation, vascular regulation and immune response
- Eicosanoids => Derivatives of Arachidonic Acids
- Metabolised by COX to precursors of prostacyclins, thromboxanes
- Metabolised by LOX to leukotriene precursors
5
Q
AA Derivatives
A
- Common in neuronal signalling (Aspartate, Glutamate etc)
- Vasodilation (Nitric Oxide)
- NO generated from Arginine, intra and extra cellular messenger
- Catalysed by 3 NOS isoenzymes
6
Q
Nucleotides
A
- Guanosine and Adenosine phosphate derivatives are often downstream of other signalling molecules
7
Q
Organic Chemicals
A
- Primarily neurotransmitter
- Catecholamines (Monoamine): => Adrenaline, Noradrenaline, Dopamine,
- Derivatives of phenylalanine and tyrosine
- Serotonin => modulates mood, memory, and physiological processes: vasoconstriction, bone metabolism etc
- Serotonin Synthesis: hydroxylation and decarboxylation of tryptophan
- Acetylcholine
8
Q
Signalling Molecules - Storage, release and transport
A
- Neurotransmitters => stored in vesicles and released into synapses as active molecules
- P/P as prepro forms
- Steroid hormones require carrier proteins globulin and serum albumin
9
Q
Signalling Molecules - Inactivation
A
- Biochemical signals must be inactivated to prevent excessive cell stimulation and allow the cell to react to new signals
- Peptides/proteins are degraded through peptidases
- Steroid hormones are degraded by CYP450 enzymes
- Eicosanoids are often degraded locally
- Neurotransmitters are recycled back into pre-synaptic vesicles or are degraded by enzymes
10
Q
Signalling Receptors
A
- Cells respond to changes via receptors that trigger molecular responses
Signals = temperature, light, pressure, pain and chemicals - Chemical Receptor Classes: Ion channels, GPCRs, Receptor Kinases, Cytosolic/Nuclear receptors
- Differential expression of receptors in different cells allows organs to respond differently to specific biochemical responses.
11
Q
Receptor Structure
A
- All receptors are proteins
- All membrane bound receptors have extracellular and transmembrane domains
- Cytosolic receptors enter the nucleus to start the process of transcription
12
Q
Receptor Specificity
A
- Specific to ligands
- Crucial to regulate cell biochemistry physiologically and medically
- Agonists activate a receptor response
- endogenous (hormones) or exogenous (drugs)
- Antagonists block a receptor response (inhibitor/drug)
13
Q
Receptor Sensitivity & Saturability
A
- ligands binding to receptors have an affinity constant: Kd
- Kd = concentration when 50% receptors are occupied with ligand
- Low Kd = High affinity/High Kd = Low affinity
- When all receptor sites are occupied the cell will be maximally simulated and the system is saturated
- The cell can over/under-express the receptor to alter its Kd
14
Q
Signal Transduction
A
1) Change of shape of the receptor bound by ligand
2) Downstream molecular events in the cell cytoplasm
16
Q
GPCRs
A
- G-proteins (guanine nucleotide-binding proteins) associated to the transmembrane domain areheterotrimeric: alpha, beta, gamma subunits
- Largest and most diverse group of membrane receptors in eukaryotes.
1) Inactive GPCR: GDP binds to the alpha subunit
2) change in the conformation of the GPCR activates the G protein
3) GTP replaces the GDP bound to the alpha subunit and detaches the beat/gamma subunits from the
4) GTP-beta/gamma complex activates cytosolic enzymes
5) Change in cytosolic concentration of 2nd messengers (cAMP, IP3, DAG, Ca2+)= Transduction
