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Apex > Cell Communication > Flashcards

Cell Communication Flashcards

1
Q

What is the intracellular response to extracellular signals?

A

Cell signaling

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2
Q

What is the conversion of information into a chemical change called?

A

Transduction

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3
Q

What four forms does information arrive in at cells?

A

Purely physical: (energy), light, sound, heat, pressure, and electricity

Chemical: neurotransmitters, hormones, eicosanoids, drugs, toxins

Cellular: gap junctions

Extracellular matrix molecules: collagen (think of platelet adhesion)

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4
Q

What are the 3 main methods of intracellular communication?

A

Endocrine
Paracrine
Autocrine

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5
Q

What are the strongest bonds to weakest? (Think chemistry)

A

Covalent > ionic > hydrogen > hydrophobic > van der Waals

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6
Q

What is it called when an enzyme associated with a signal receptor is activated and in turn, catalyzes the activation of many molecules of a second enzyme, each with activates a 3rd enzyme!?!

A

Amplification

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7
Q

What is it called when a transduction has a cell-specific receptor?

A

Specificity and sensitively

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8
Q

What is the ability of a signal-transfixing system to receive multiple signals and produce a unified response appropriate to the cell’s needs?

A

Integration

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9
Q

What two types of feedback are there?

A

Positive and negative

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10
Q

What is it when multiple components of signaling pathways are brought together on scaffold proteins to increase their local concentration and effects?

A

Compartmentalization

(I.e. ryanodine receptors)

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11
Q

What happens when a signal is present continuously?

A

Desensitization

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12
Q

What is the general flow through a G-protein-coupled receptor?

A

First Rabbit Eats the Sweetest Carrots

First messenger >
Receptor >
Effector >
Second messenger >
Cellular response

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13
Q

What are the 6 steps to the signaling pathway?

A

“Run To The Market Randy Travis!”

Recognition ~ of the signal by the receptor

Transduction ~ excellular message into an intracellular signal

Transmission ~ second messenger’s signal to the appropriate effector

Modulation ~ on/off switch

Response

Termination ~ usually accomplished by feedback control

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14
Q

What is it called when any chemical binds to a receptor?

A

Ligand (first messenger)

Causes a conformational change and initiates the signaling sequence

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15
Q

What is the final consequence of recognition and transduction?

A

Generation of a second messenger and/or the activation of a catalytic cascade

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16
Q

What two phases usually occur during transmission?

A

Amplification and integration

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17
Q

What are considered two methods of modulation?

A

Enzymatic phosphorylation or dephosphorylation reactions

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18
Q

How is feedback often accomplished?

A

Feedback control

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19
Q

This is the most common control system for maintaining homeostasis. If a factor is excessive or deficient, this feedback loop will produce a series of effects to reverse the change and return the value to its set point.

A

Negative feedback loop

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20
Q

In this control mechanism, a change in some factor will produce an enhanced or accelerated change in the same direction. Know as “vicious cycles”

A

Positive feedback loop

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21
Q

What are 3 examples of a positive feedback loop?

A

Childbirth
Blood coagulation
Opening of voltage-gated Na* channels to initiate and propagate

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22
Q

What is endocrine cell signaling?

A

A signaling molecule is secreted by a endocrine cell and transported through the circulation where it acts on a distant target cell

***hormones

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23
Q

What is paracrine cell signaling?

A

A chemical signal molecule is released by one cell and acts locally to regulate the behavior of a neighboring cell.

**neurotrasmitter cell signaling

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24
Q

What is autocrine cell signaling?

A

A cell responds to a signaling molecule that it also produced!

***NE stimulating alpha-2 receptor

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25
Q

What family of enzymes catalyzes the addition of a phosphate group to a molecule?

A

Kinases

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26
Q

What are examples of small hydrophilic chemical messengers?

A

Amino acids (GABA)
Biogenic amines (NE)
Choline Esters (Ach)
Iodothyronines (T4 & T3)

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27
Q

What are examples of lipophilic chemical (non polar) messengers?

A

Steroids
Eicosanoids
Miscellaneous

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28
Q

How many times does a G protein-coupled receptor span the plasma membrane?

A

7

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29
Q

About 1/2 to 2/3 of all drugs target what type of receptor?

A

G protein

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30
Q

How are G proteins turned on?

A

Ligand binds to the receptor-binding site

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31
Q

How are G-proteins turned off?

A

Intrinsic GTPase activity in the alpha subunit

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32
Q

What is the first messenger signal at the G protein-coupled receptor terminated by?

A

Diffusion of the ligand away from the receptor

Chemical modification of the receptor (typically phosphorylation) to desensitize the receptor

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33
Q

What does the Gs stand for?

A

G protein family

“S” is for stimulatory
*** alpha-a unit STIMULATES adenylyl cyclase

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34
Q

What does Gi stand for?

A

G protein family

“I” is for inhibitory! Alpha-i subunit inhibits adenylyl cyclase

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35
Q

What is Gq?

A

G protein family

“q” stimulate phospholipase (PLC)
Q = “Queer PLaCes”~ odd or different

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36
Q

What is the substrate of adenylyl cyclase? (Enzyme reaction)

A

ATP > cAMP

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37
Q

What is what is the substrate to Phospholipase C? Enzyme reaction..

A

PIP2 > IP3 + DAG

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38
Q

What is the substrate to phospholipase A2? Enzyme reaction?

A

Phospholipid > arachiodonic acid

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39
Q

What is arachidonic acid the precursor to?!

A

Prostaglandins
Thromboxanes
Leukotrienes
COX

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40
Q

Increased cAMP in cardiac myocytes does what?

A

Enhances contractility (beta 1 effects)

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41
Q

what does increased cAMP do in the smooth muscles of the airways and vessels?

A

Causes relaxation and dilation. (Beta 2 receptor effects)

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42
Q

Increased cAMP does what in platelets?

A

Reduces platelet aggregation.

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43
Q

What does increased cAMP do in the principal cells of the nephron?

A

Insertion of aquarium 2-water channels in the apical membrane

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44
Q

What are the two types of synapses in the human body?

A

Electrical and chemical

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45
Q

What type of responses do ionotropic receptors participate in?

A

Fast synaptic responses

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46
Q

What are examples of excitatory responses?

A

Na+ influx
Ca influx
Reduced K efflux

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47
Q

What are examples of inhibitory responses?

A

Increased K+ efflux
Cl- influx
Closure of Ca channels

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48
Q

What’s another name for transmembrane G protein-coupled receptors?

A

Metabotropic

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49
Q

What is the presynaptic terminal also called?

A

Axon terminal, synaptic bouton, and synaptic knob

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50
Q

Which protein in the docking complex of the presynaptic terminal senses calcium and leads to release of neurotransmitters?

A

Synaptotagmin

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51
Q

What is the primary neurotransmitter of peripheral efferent (motor) neural pathways?

A

Acetylcholine

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52
Q

At what sites is ACh the neurotransmitter?

A

NMJ
Autonomic ganglia
Terminal synapses of parasympathetic post ganglionic fibers
A few sympathetic post ganglionic fibers (sweat glands)
The non-neural cholinergic system

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53
Q

What is the synthesis of acetylcholine synthesis?

A

Glucose in nerve terminal > glycolysis converts glucose to pyruvate > pyruvate enters mitochondria > acetyl-CoA is created > acetyl-CoA is transported back into cytoplasm > choline is actively transported into presynaptic terminal > choline acetyltransferase catalyzes the formation of ACh from acetyl-CoA + choline

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54
Q

What is the rate limiting step to ACh synthesis?

A

Choline transport

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55
Q

What enzyme hydrolyzes ACh to acetate + choline?

A

Acetylcholinesterase

56
Q

Where are NmAChRs found?

A

Skeletal muscle at the neuromuscular junction

**end plate depolarization and skeletal muscle contraction

57
Q

Where are NnAChRs found?

A

Autonomic ganglia, chromaffin cells, and CNS

***Depolarization of post-synaptic post-ganglionic neuron

Secretion of catecholamines

Arousal, attention, and analgesia

58
Q

What two agonist binding site must occur to elect a reaction in a nicotinic receptor?

A

Must bind with two alpha subunits

59
Q

Where are M1 receptors found?

A

Autonomic ganglia (**excitatory response)

CNS (**arousal, attention, analgesia)

60
Q

Where are M2 receptors found?

A

Heart: nodal tissue (slowed spontaneous depolarization ~ decreased chronotropy)

Heart: contractility: (decreased contractility ~ decreased dromotropy)

61
Q

Where are M3 receptors found?

A

Smooth muscle (contraction)

GI (increased secretions)

62
Q

Where are M4 receptors found?

A

CNS (**presynaptic auto-receptors > negative feedback to suppress ACh release)

**like alpha 2 receptors

63
Q

Where are M5 located?

A

CNS (promotes dopamine release, dilation of cerebral arteries)

64
Q

Which G receptor is associated with M1, M3, M5?

A

Gq ~ odd number for an odd/Queer receptor.

***Gq > PLC > IP3 > DAG > increase in Ca

65
Q

What M receptors are associated with Gi?

A

M2 and M4

**Gi is inhibitory!! > inhibits AC > decrease in cAMP

66
Q

What does the NMDA receptor have binding sites for?

A

Glutamate
Glycine
Magnesium
Ketamine

67
Q

What is the primary excitatory neurotransmitter in the brain?

A

Glutamate

  • motor neuron activation, pain pathway, hyperanalgesia pathway, memory formation, and cerebral neurotoxicity
68
Q

What is the primary inhibitory neurotransmitter in the brain?

A

GABA

*play a role in arousal, attention, memory formation, anxiety, sleep, and muscle tone

69
Q

What is the primary inhibitory neurotransmitter in the spinal cord?

A

Glycine

Renshaw cells > form inhibitory synapses on alpha motor nerves >self-limiting firing of alpha motor nerves

70
Q

What two amino acids are interconvertible through the kreb’s cycle? The brain can easily convert one to the other!

A

GABA and Glutamate

71
Q

What is glutamate synthesis?

A

Glutamine is transported out of a glial cell > transported into presynaptic terminal > in terminal, glutamine is converted to glutamate by glutaminase (on mitochondria membrane) > glutamate is transported and stored in vesicles

72
Q

What is the rate limiting step in glutamate synthesis?

A

Glutaminase activity

73
Q

What are the 3 types of ionotropic glutamate receptors?

A

N-methyl-D-asparate (NMDA)
a-amino-3-hydroxy-5-methyl-4-isoxazeole-propionic acid (AMPA)
Kainate receptors

74
Q

What does full activation of a NMDA receptor requires what?

A

It’s A LOT!
Binding of TWO glutamates
Two glycine molecules
AND a depolarizing voltage change

“3 safety locks”

75
Q

the phencyclide binding site in the NMDA receptor is a binding site for what meds?

A

PCP and ketamine

76
Q

What is it called when you experience neuronal injury initiated by excessive glutamate receptor activity?

A

Excitotoxicity

77
Q

What pathological disease processes is excitotoxicity (as in the NMDA) implicated in?

A

Huntington’s disease
Alzheimer’s disease
ALS
Stroke and trauma
Hyperanalgesia
Epilepsy

78
Q

What is GABA synthesis?

A

Glutamine enters presynaptic terminal > in mitochondria, glutaminase converts glutamine to glutamate > back in cytoplasm, GABA is formed by decarboxylation of glutamate (this is by glutamic acid decarboxylase [GAD])

***GAD is NOT present in neurons that use glutamate as a neurotransmitter

79
Q

What are GABAa receptors?

A

Ionotropic
* ligand gates Cl- channels.
> activated by the binding of two GABA molecules

***GABAa are the target of:
>benzos
> barbs
> prop
> etomidate
> volatile anesthetics
> majority of hypnotics!!!

80
Q

What are GABAb receptors?

A

Metabotropic

> inhibitory still

81
Q

What type of receptor is glycine only?

A

Ionotropic

**Co-activator of NMDA

82
Q

What is a rare neurological disease that results from mutations in the glycine receptor?

A

Human startle disease

83
Q

What two binding sites are located IN the NMDA RECEPTOR CHANNEL PORE?

A

Mg
ketamine/PCP

84
Q

What are norepinephrine and epinephrine metabolized to?

A

Vanillylmandelic acid

85
Q

What are the 5 biogenic amine neurotransmitters? **hint ~they have “ine” in them

A

> dopamine
norepinepherine
epinephrine
histamine
serotonin (5HT)

86
Q

What are most biogenic amine neurotransmitter receptors?

A

Metabotropic

87
Q

What is the exception to most amine neurotransmitters being Metabotropic receptors? What specific amine?

A

Serotonin ~ 5-HT3 receptor

88
Q

What are all biogenic amine neurotransmitters synthesized from?

A

Amino acids

89
Q

What are ALL catecholamines synthesized from?

A

Tyrosine

90
Q

What is serotonin synthesized from?

A

Tryptophan

91
Q

What is histamine synthesized from?

A

Histidine

92
Q

What does hydroxylation do?

A

Add an OH group

93
Q

What does decarboxylation do?

A

Removes a CO2 group

94
Q

What is the order from Tyrosine to Epinephrine?

A

Tyrosine > L-Dopa > dopamine > norepinephrine > epi

Our friend Tyler (tyrosine) who loved hydroxycut (tyrosine hydroxylase) was such a Loser AND Dope (L-dopa). He got smart and started to remove Carbs (decarboxylase) from his diet but was still a dope (dopamine). Eventually he drank a some water, hydrated (dopamine hydroxylase) and became like N-E-other (norepinephrine) guy in school. Unfortunately he did some meth (n-methyltransferase) and became the EPI-tome of another high school dropout.

95
Q

What is tyrosine hydroxylated to form?

A

L-DOPA

(Done by tyrosine hydroxylase)
***rate limiting step in catecholamine synthesis

96
Q

What is L-Dopa decarboxylated by to form dopamine?

A

L-amino acid decarboxylase

97
Q

What catalyzes dopamine to form norepinephrine?

A

Dopamine-B-hydroxylase

98
Q

What catalyzes norepinephrine to epi?

A

N-methyltranferase

99
Q

Where does the conversion of NE to E happen?

A

Cytoplasm

100
Q

Where does the conversion from dopamine to NE happen?

A

Vesicle

101
Q

Where does the conversion from tyrosine to L-Dopa happen

A
102
Q

What two enzymes metabolize catecholamines?

A

Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT)

103
Q

What does MAO-A preferentially degrade?

A

Dopamine, epinephrine, and serotonin

104
Q

What does MAO-B preferentially degrade?

A

Degrades dopamine more rapidly than serotonin and NE

105
Q

What is the end-product to catecholamine metabolism?

A

Vanillymandelic acid

(To become this, NE and Epi must be processed by BOTH MAO and COMT ~ order of which doesn’t matter)

106
Q

What is the most common screening test to establish the diagnosis of pheochromocytoma?

A

Catecholamine metabolites in the urine!

107
Q

What is serotonin synthesis?

A

Tryptophan > (tryptophan hydroxlase) > 5-hydroxytryptophan > (L-amino acid decarboxylase) > serotonin

108
Q

What are high levels of 5-HIAA consistent with?

A

Carcinoid tumors!

**5-HIAA is metabolic byproduct of serotonin.

109
Q

Where is histamine synthesize in the periphery?

A

Mast cells and basophils

110
Q

What is the most important mechanism by which catecholamines are removed from the synaptic cleft?

A

Reuptake

111
Q

Where is the largest concentration of dopamergic neurons located?

A

Substantia nigra

*crucial for coordinating mov
* degeneration or dopaminergic neurons causes Parkinson’s

112
Q

What are the 5 types of dopamine receptors?

A

D1, D2, D3, D4, D5

113
Q

Which dopamine receptors activate PKA via adenylyl cyclase and cAMP?

A

D1 and D5!

114
Q

Which dopamine receptors inhibit adenylyl cyclase and reduce PKA activity ~ this leading to decreased neuronal activity?

A

D2, D3, D4

115
Q

What are the 3 main classes of adrenergic receptors?

A

Alpha 1:( a1A, a1B, a1D)
Alpha 2: (a2A, a2B, a2C)
Beta: (B1, B2, B3)

116
Q

What does NE preferentially bind to?

A

a1, a2, and B1

117
Q

what does Epi predominately stimulate at low concentrations?

A

Beta effects

118
Q

What does Epi stimulate at higher concentrations?

A

Alpha 1 effects

119
Q

What is the 5-HT3R?

A

An ionotropic serotonin receptor.

Nonselective cation channel ~ activation leads to rapid membrane depolarization

***this is where Zofran works as an ANTAGONIST

120
Q

What are the two purine bases?

A

Adenine
Guanosine

121
Q

What is a nucleotide?

A

Molecule composed of a 5 Carbon sugar (Pentose), a nitrogen base, and a least one phosphate group.

(ATP, ADP, AMP, GMP, GDP)

122
Q

What are the main purinergic transmitters?

A

ATP, ADP, and adenosine

123
Q

What is the mechanism of action of adenosine?

A

Protects tissues from damage. A strong increase in adenosine levels in the extracellular fluid is an emergency signal indicates an acute oxygenation deficiency (stoke, MI)

124
Q

What does NO arise from?

A

Oxidation of guanidino group of L-arginine

125
Q

What does generation of NO require?

A

NADPH ~ molecular oxygen

126
Q

What are some traits about necrosis?

A

Processes: uncontrolled
Cell size: enlarged (swelling)
Nucleus: pyknosis > karyolysis
Plasma membrane: disrupted
Cellular contents: enzymatic digestion ~ may leak out of cell.
Adjacent inflammation: frequent

127
Q

What are some traits about apoptosis?

A

Processes: genetically programmed
Cell size: reduced (shrinkage)
Nucleus: fragmentation
Plasma membrane: intact
Cellular contents: intact
Adjacent inflammation: no

128
Q

What four ways does B1 stimulation support cardiac performance??

A

> Positive inotropy (contractility)
Positive lusitropy (“getting loose”! Relaxation)
positive chronotropy (heart rate)
positive dromotropy (conduction)

129
Q

What does NO activate in smooth muscle?

A

Soluble guanylyl cyclase (sGC) ~ this catalyzes the conversion of GTP to cGMP

130
Q

What is the synthesis of nitric oxide (NO)

A

Stress/ACh/serotonin/etc… stimulate cell and increase intracellular Ca > Ca combines with calmodulin and activates endothelial nitric oxide syntheses (eNOS) > eNOS produces NO from L-arginine > NO diffuses into smooth muscle cells and activates guanylyl cyclase

131
Q

What is in the central nerve system?

A

Brain and spinal cord

132
Q

What is in the peripheral nervous system?

A

All nerves and sensory structures outside of brain and spinal cord

133
Q

How is the peripheral nervous system divided?

A

Somatic and autonomic

> Somatic: voluntary control of muscles
Autonomic: involuntary control of glands and smooth muscle

134
Q

How is the autonomic system divided?

A

Sympathetic

Parasympathetic

And enteric

135
Q

What is the SNS classically described as?

A

“Fight or flight”

136
Q

What is the PNS system classically called?

A

“Feed and breed”

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