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foundations 2 > exam 2 > Flashcards

exam 2 Flashcards

1
Q

Guanylyl cyclades use _______ ______ as a secondary messenger

A

cyclic GMP

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2
Q

Guanylyl cyclades convert ______ into 3’,5’-cyclic monophosphate (cyclic GMP, cGMP)

A

GTP

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3
Q

cGMP ________ cGMP-dependent protein kinase G (PKG)

A

activates

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4
Q

PKG _________ serine and threonine residues of downstream target proteins

A

phosphorylates

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5
Q

What are the two types of guanylyl cyclases

A

membrane-bound, and soluble

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6
Q

what type of guanylyl cyclase is a homodimer and responds to natriuretic peptides

A

membrane-bound

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7
Q

what type of guanylyl cyclase is a heme-containing enzyme, responds to intracellular NO concentrations, and present in the heart, blood vessels, leads to smooth muscle contraction

A

soluble

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8
Q

an increase in blood volume triggers the atrium to release what

A

atrial natriuretic factor

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9
Q

what triggers guanylyl cyclase activity in collecting ducts of kidneys

A

atrial natriuretic factor binding

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10
Q

where does ANF bind to ANF-receptors

A

collecting ducts of kidneys and vascular smooth muscle

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11
Q

increase in cGMP in collecting triggers what that lowers blood volume

A

renal excretion of Na+ and water

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12
Q

what activates muscarinic GPCR endothelial on cells via Gq, stimulating IP3 synthesis and Ca2+ release

A

Ach

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13
Q

what activates NOS to produce NO from arginine - activates guanylyl cyclase to produce cyclic GMP

A

Ca2+

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14
Q

what triggers the smooth muscle to relax, increasing blood flow through the vessel

A

cGMP

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15
Q

how is nitric oxide produced

A

nitric oxide synthase

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16
Q

cytosolic (soluble) guanylyl cyclase has what prosthetic group

A

heme

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17
Q

nitric oxide is synthesized from arginine via what in nearby cells

A

NO synthase

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18
Q

an increase in cGMP stimulates cGMP-dependent kinase which decreases cytosolic Ca2+ and then the heart:

A

decreases force of contractions

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19
Q

in vascular smooth muscle~ activation of PKG leads to ________ by phosphorylating

A

vasodilation

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20
Q

VDCC (voltage-dependent calcium channels) leads to what

A

a decrease influx of Ca2+

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21
Q

phospholamban which modulates SR Ca2+ pump leads to

A

re-uptake of Ca2+ into intracellular stores

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22
Q

Ca2+-activated K+ channel–> hyper polarization –> closes L-type Ca2+ channels leads to

A

decrease Ca2+ influx

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23
Q

what causes mediated Ca2+ release from intracellular stores

A

inhibiting IP3

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24
Q

what is produced via Ca2+ dependent NOS

A

NO

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25
Q

nitric oxide synthase (NOS) exists in 3 isoforms

A

NOS2 (inducible), NOS3 (constitutive), NOS1 (constitutive)

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26
Q

what are examples of NOS2

A

macrophages and other cells

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27
Q

what are examples of NOS3

A

‘endothelial’, platelets

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28
Q

what are examples of NOS1

A

neuronal forms (CNS, ANS)

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29
Q

nitroglycerin (NTG) and nitrovasodilators give long-lasting relief from what

A

angina

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30
Q

NTG causes vasodilation and what

A

decrease myocardial O2 demand

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31
Q

what drug was developed as a vasodilator for CVDs

A

viagra

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32
Q

phosphodiesterase (PDEs) convert cGMP to inactive 5’-GMP terminates what

A

cGMP effect

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33
Q

what is a more selective inhibitor for PDE V isoform found in the penis

A

sildenafil

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34
Q

sildenafil causes what

A

cGMP levels to remain high in the penis, causing vasodilation

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35
Q

penile erection is initiated by what

A

NO release from neurons and endothelial cells

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36
Q

PDE5 inhibitors enhance signaling through what pathway

A

NO-guanylyl cyclase-cGMP-PKG pathway

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37
Q

activation of PKG leads to what

A

relaxation of cavernosal smooth muscle then engorgement of the corpus cavernous with blood

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38
Q

gated ion channels regulate what

A

transport of ions across cell membranes

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39
Q

gated ion channels respond to

A

changes in the membrane potential and ligand binding to specific receptor sites

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40
Q

voltage-gated sodium channels, nicotinic acetylcholine (Ach) receptor, ionotropic glutamate receptor, and gamma aminobutyric acid receptor A: these are all examples of what

A

roles gated ion channels play in the nervous system

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41
Q

passive ion fluxes down cellular electrochemical gradients are regulated by a large family of ____ ______ located in the membrane

A

ion channels

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42
Q

voltage-activated, ligand-activated, store-activated, stretch-activated, and temperature-activated channels are all another way to classify what

A

ion channels

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43
Q

changes in the flux of ions across the plasma membrane are critical regulatory events in what cells

A

excitable and non-excitable

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44
Q

the inside of the cell is typically ________ ________ compared with the outside: Vm ___ to ___mV

A

negatively charged; -50, -70

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45
Q

the membrane potential is largely due to what transport of cations by Na+K+ ATPase: 3 Na+ out 2 K+ in

A

assymmetric transport

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46
Q

flow of ionic species across the membrane depends on what

A

its concentration gradient and overall electrical potential

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47
Q

membranes are electrically polarized (t/f)

A

true

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48
Q

to establish the electrochemical gradients required to maintain a membrane potential all cells express what

A

ion transporters for Na+, K+, Ca2+, and Cl-

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49
Q

excitable tissues such as nerve and muscle to generate and transmit electrical impulses, non-excitable cells to trigger biochemical and secretory events, and all cells to support a variety of secondary symport and anti port processes all use what

A

the electrochemical gradient established

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50
Q

nerve signals within nerves propagate as what

A

electrical impulses

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51
Q

propagation of the impulse involves what

A

opening of voltage-gated Na+ channels

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52
Q

opening of voltage-gated Ca++ channels at the end of the axon triggers the release of what

A

neurotransmitter- Ach

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53
Q

Ach opens what on the receiving cell

A

the ligand-gated ion channel

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54
Q

what channels in the nerve and muscle cells generate action potential (AP) that depolarize the membrane from its resting potential of -70mV to +20mV within milliseconds, composed of 3 subunits, a pore-forming a subunit and 2 regulatory b subunits

A

voltage-gated Na+ channels

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55
Q

what are targets for many drugs and toxins (tetrodotoxin and saxitoxin)

A

voltage-gated Na+ channels

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56
Q

what block the pore, inhibit depolarization and therefore block the sensation of pain

A

local anesthetics

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57
Q

what is composed of large a subunit and 3 regulatory subunits (B, o, y subunits)

A

voltage-gated Ca2+ channels

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58
Q

voltage-gated Ca2+ channels _______ an action potential- AP (as in the pacemaker cells of the heart)

A

initiate

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59
Q

voltage-gated Ca2+ channels modify the _______ and ________ of an AP initiated by fast V-G Na+ channels

A

shape and duration

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60
Q

voltage-gated Ca2+ channels initiate Ca2+ influx that stimulates ________ ______ in the nervous system

A

neurotransmitter release

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61
Q

voltage-gated Ca2+ channels initiate Ca2+ influx controls what in cardiac tissue

A

heart rate and impulse conduction

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62
Q

where are L-type Ca2+ channels located in many cells

A

plasma membrane

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63
Q

what is the main Ca2+ source for contraction in smooth and cardiac muscle

A

VDCCs

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64
Q

what are used to treat hypertension, angina, and cardiac arrhythmias (nifedipine and verapamil)

A

CCB

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65
Q

what ionotropic receptors are involved mainly in fast synaptic transmission

A

ligand-gated ion channel

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66
Q

what is the most common structure of ligand-gated ion channels (transmembrane helices arranged around a central aqueous channel)

A

heteromeric assemblies of 4 or 5 subunits

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67
Q

voltage-gated K+ channels are blocked by what

A

TEA and 4-AP

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68
Q

what K+ channels allow K+ to pass inwards easily than outwards

A

inwardly rectifying

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69
Q

what K+ channels outward rectifying exert depolarizing influence, opposing any tendency to excitation-may mediate action of volatile anesthetics such as isoflurane

A

two-pore domain

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70
Q

what nomenclature refers to presence of first double bond from methyl end

A

omega

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71
Q

(IUPAC) refers to double bond from carboxyl (highest priority/most oxidized) end

A

delta

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72
Q

what are important fatty acid-derived molecules involved in signaling

A

eicosanoids

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73
Q

eicosanoids are derived from C2O fatty acid molecules that are derived from what

A

dietary plant fatty acids

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74
Q

consumption of what (including linoleate (18:2)) is required for proper functioning of the eicosanoid pathway

A

essential fatty acids

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75
Q

_______ cannot make double bonds closer to the end than the Delta-9 position

A

mammals

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76
Q

where do we get linoleate (18:2) from? this installs the 2nd double bond

A

plants

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77
Q

linoleate (18:2) is an essential fatty acid, which means we get it from where

A

ingesting it

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78
Q

desaturation to gamma-linolenate (18:3), elongation to eicosatrienoate (20:3), desaturation to arachidonate (20:4), and performed by mixed function oxidases and fatty acid elongates~ in the human body these are all undergone by what

A

linoleate

79
Q

linoleate is desaturated, elongated, desaturated to what in the human body

A

arachidonate (20:4)

80
Q

plant and fish-derived fatty acid supplements provide what effects

A

cardioprotective and triglyceride lowering

81
Q

corn oil, safflower oil, and sunflower oil provide the omega-6 _______ _____

A

linoleic acid (18:2)

82
Q

linoleic acid alters what

A

1-series prostaglandins

83
Q

fish oils provide which omega-3 fatty acids

A

eicosapentaenoic (C20:5) and docosahexaenoic acids (C22:6)

84
Q

fatty acid supplements alter eicosanoid profiles, which results in reductions of what

A

myocardial infarction and sudden cardiac arrest

85
Q

what was the first FDA-approved EPA-only omega 3 (2012)

A

Icosapent ethyl (Vascepa)

86
Q

DHA (22:6) has been shown to increase what

A

LDL (bad) cholesterol

87
Q

EPA only, has been shown to lower ________ without raising LDL (bad) cholesterol

A

triglycerides

88
Q

eicosanoids are made from what

A

arachidonate

89
Q

________ are potent short-range hormones

A

eicosanoids

90
Q

_________ is produced from the arachidonate that is incorporated into the phospholipids of membranes

A

eicosanoids

91
Q

in response to stimuli (hormone, etc.) ____________ is activated and attacks the C-2 fatty acid, releasing arachidonate

A

phospholipase A2

92
Q

what is an omega-6 fatty acid derived from linoleum acid, and comes from the diet, but mostly from phospholipids

A

arachidonic acid (20:4)

93
Q

what strips arachidonic acid off of phospholipids in the cell membrane

A

phospholipase A2

94
Q

phospholipase A2 family consists of how many groups

A

15

95
Q

what phospholipase has high affinity for AA, most is released via this enzyme

A

cytosolic PLA2 (c-PLA2)

96
Q

what phospholipase is responsible for long-term stimulation or sustained release of AA

A

Secretory PLA2 (s-PLA2), Ca2+-dependent

97
Q

what phospholipase are most AA released via this enzyme is ligated back to phospholipids

A

Ca2+-independent PLA2 (I-PLA2)

98
Q

cyclooxyrgenase (COX-1/COX-2) give the ______ _____

A

cyclic prostanoids

99
Q

lipoxygenase results in what

A

leukotrienes and lipoxins

100
Q

eicosanoid profiles differ based on cell, induction and what?

A

fatty acid substrate

101
Q

PGH2 synthase is a cyclooxygenase/peroxidase enzyme that functions where

A

the smooth ER

102
Q

what is step 1 in the conversion of arachidonate to PGs and TXs

A

PGH2’s cyclooxyrgenase activity adds 2 O2 to form PGG2

103
Q

what is step 2 in the conversion of arachidonate to PGs and TXs

A

PGH2’s peroxidase activity converts peroxide to alcohol, creates PGH2

104
Q

_______ inhibit cyclooxyrgenase (COX) activity

A

NSAIDs

105
Q

what are the two isoforms of PGH2 synthase

A

COX-1 and COX-2

106
Q

what catalyzes synthesis of prostaglandins that regulate gastric mucin secretion

A

COX-1

107
Q

what catalyzes synthesis of prostaglandins that mediate pain, inflammation, and fever

A

COX-2

108
Q

what is an irreversible inhibitor that acetylates a Sea in active site blocking it in both COX isozymes

A

aspirin (acetylsalicylate)

109
Q

what are competitive inhibitors that resemble substrate; also block active site in both isozymes

A

ibuprofen and naproxen

110
Q

synthesis of leukotrienes begins with _________

A

arachidonate

111
Q

in prostaglandin nomenclature the two-letter code signifies which ______ the molecule belongs to

A

class

112
Q

the subscript “n” in prostaglandin nomenclature means what

A

the number of double bonds it has

113
Q

what are two examples of prostanoids (cyclooxyrgenase pathway)

A

PGn (prostaglandins) and TXn (thromboxane)

114
Q

what are two examples of lipoxins and leukotrienes (lipoxygenase pathway)

A

LTn (leukotriene) and LXn (lipoxins)

115
Q

which series includes omega-6 fatty acids contributing, linoleate (18:2) is eaten and desaturated in our bodies to y-linolenate (18:3), y-linolenate (18:3) is extended in our bodies to eicosatrienoate (20:3), and eicosatrienoate forms this prostanoid and lipoxins

A

series 1

116
Q

which series is mostly inactive

A

series 1

117
Q

which series includes membrane-bound eicosatetraenoate/arachidonate (20:4) is hydrolyzed by phospholipase A2, and free arachidonate then goes to form prostanoids and lipoxins

A

series 2

118
Q

which series have most of the activity in the human body

A

series 2

119
Q

vasoconstriction, inflammation, pain, induce sleep, blood coagulation, reproduction all occur due to what

A

series 2

120
Q

omega-3 fatty acids (eicosapentaenoic acid, EPA) lead to formation of _____ __ prostanoids and leukotrienes

A

series 3

121
Q

which series prostanoids and leukotrienes are weaker than the series 2

A

series 3

122
Q

cyclooxyrgenase 1 and 2 (COX-1 and COX-2) convert AA into what?

A

endoperoxides

123
Q

COX-1 and COX-2 are also known as what?

A

PGH-1 and PGH-2

124
Q

COX-1 and COX-2 are _______

A

isoforms

125
Q

what is constitutively expressed in most cells and is the isoform responsible for PGs that enable gastric mucus production

A

COX-1

126
Q

what is inducible, appears to be the more valuable target for NSAIDs medication, and is the isoform responsible for PGs involved in inflammation, pain, and fever

A

COX-2

127
Q

what is the most selective COX-2 inhibitor that is still available (as of 2012) with monitoring

A

celecoxib (Celebrex)

128
Q

COX-1 and COX-2 convert AA to what

A

PGG2 and PGH2

129
Q

COX-1 and COX-2 make what and then hydroxylate it to PGH2

A

prostaglandin G2 (PGG2)

130
Q

what is the branch point for many prostanoids

A

PGH2

131
Q

endoperoxides are unstable and are quickly metabolized into other what?

A

prostacyclins and thromboxanes

132
Q

what results in “housekeeping” prostanoids, such as gastric mucin production

A

COX-1

133
Q

what results in endothelial vascular prostacyclin PGI2 (important) and normal renal development and function

A

COX-2

134
Q

PGH2 is cyclized via:

A

TX/PG synthases and isomerases

135
Q

enzymes are cell-specific and most cells produce how many types or prostanoids

A

1-2

136
Q

PGs differ based on constituents of what

A

cyclopentane ring and number of double bonds

137
Q

what undergo different cyclization and isomerizations from the PGs

A

TXs

138
Q

PGH2 is converted to PGE2 via what

A

PGE2 synthase

139
Q

How does PGE2 promote vasodilation

A

by increasing cAMP and decreasing smooth muscle intracellular calcium

140
Q

PGE2 is produced by endothelial cells in the ________

A

microvasculature

141
Q

dinoprostone is an important PGE2-based relaxant used for what

A

induce labor

142
Q

what does PGF2a cause

A

smooth muscle contraction

143
Q

latanoprost is an ophthalmic formulation used to do what

A

decrease intraocular pressure and decrease ocular hypertension

144
Q

what is a very powerful vasodilator and inhibitor of platelet aggregation

A

PGI2

145
Q

PGI2 is synthesized by vascular endothelium and is important in what

A

renal development

146
Q

synthetic PGI2 epoprostenol is used to treat what

A

pulmonary hypertension

147
Q

what causes muscle contraction and stimulates smooth muscle mitosis

A

thromboxane A2 (TXA2)

148
Q

thromboxane A2 primarily causes what

A

aggregation of platelets and vasoconstriction

149
Q

how are lipoxins formed

A

via 5-,12- and 15- lipoxygenases (LOX)

150
Q

what is 5-LOX activated by

A

5-LOX-activating protein (FLAP)

151
Q

5-LOX/FLAP oxygenate AA to what

A

5(s)-HPETE

152
Q

5’-LOX converts 5(s)-HPETE to what

A

LTA4

153
Q

LTA4 is then hydrolyzed (LTB4) or conjugated with __________

A

glutathione (LTC4)

154
Q

degradation of LTC4 leads to what

A

LTD4, LTE4

155
Q

_______ are important cell signaling mediators

A

leukotrienes

156
Q

________ are released from leukocytes and mast cells/dendritic cells

A

leukotrienes

157
Q

leukotrienes mediate in what

A

anaphylactic shock, asthma, and cardiovascular disease

158
Q

where are LTC4 and LTD4 potent vasoconstrictors

A

the airways

159
Q

action of these leukotrienes increase what

A

mucus secretion

160
Q

what is a short-lived epoxide and goes on to form many lipoxins

A

LTA4

161
Q

what allows for activation of leukocytes leading to binding and crossing of endothelium

A

LTB4

162
Q

______ is also a chemoattractant for leukocytes

A

LTB4

163
Q

15-LOX-1 and 5-LOX bind what

A

omega-3 DHA

164
Q

15-LOX-1 and 5-LOX convert omega-3s into what

A

resolvins

165
Q

what exhibit anti-inflammatory and lipid resolving effects

A

resolvins

166
Q

aspirin-triggered lipoxins are formed from what

A

aspirin-acetylated COX-2

167
Q

AA binds to aspirin-acetylated COX-2, which results in formation of what

A

15-(R)-HETE and 15-epi-LXA4 or 15-epi-LXB4

168
Q

arachidonic acid can also be converted to ________- or epoxyeicosatrienoic acids

A

hydroxy

169
Q

EETs are transformed into _____, which are less active

A

DHETs

170
Q

EETs are stored as what in membranes

A

phospholipids

171
Q

EETs activate what channels

A

smooth muscle Ca2+/K+

172
Q

EETS mediate in what

A

vasodilation and lowered BP

173
Q

eicosanoid molecules have a _____ t1/2

A

short

174
Q

eicosanoid molecules are short-range signaling molecules, acting on what tissues

A

autocrine or paracrine

175
Q

where to eicosanoid molecules primarily interact

A

G-protein coupled receptors

176
Q

activity is primarily determined by receptor type and density on a tissue surface for _______ molecules

A

eicosanoid

177
Q

the PGI2 (IP), PGF2a (FP), and TXA2 (TP) receptors exist as what in humans

A

single gene variants

178
Q

how many types of PGE2 receptors are there

A

4

179
Q

two different versions of what receptors exist

A

LTB and LTC

180
Q

IP and EP2/EP4 receptors cause what

A

smooth muscle relaxant effects

181
Q

TXA2 and PGF2a bind to what receptors respectively

A

TP and FP

182
Q

The TP and FP receptors primarily increase what levels

A

inositol triphosphate (IP3)

183
Q

what is produced in the endocrine tissues and exert their effects on other tissues (original definition)

A

hormones

184
Q

hormones can exert effects on ________ cells (paracrine) and on the same cell (autocrine)

A

adjacent

185
Q

how are hormonal effects achieved

A

hormone-receptor interactions

186
Q

regulation of energy storage, production, and utilization; the adaptation to new environments or conditions of stress; the facilitation of growth and development; the maturation and function of the reproductive system are all major functions of what

A

hormones

187
Q

what are extracellular chemical signals

A

hormones

188
Q

hormones must transmit their signal across the ______ _______ in some fashion

A

lipid bilayer

189
Q

some hormones undergo facilitated diffusion and bind to what

A

intracellular receptors (Group I)

190
Q

some hormones bind on the surface and initiate intracellular signal cascades

A

Group II hormones

191
Q

used to treat patients with elevated serum cholesterol

A

statins

192
Q

the statins resemble mevalonate and are competitive inhibitors of what

A

HMG-CoA reductase

193
Q
A

foundations 2 (1 decks)

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