drugs of biochem Flashcards
Ouabain (Strophantine – cardiac glycosides)
potent inhibitor of na k pump.
secondary transporter is slowed down (na/ca antiport)
ca levels increase in heart, leading to positive ionotropic effect.
t n p and a domains of p atapse
T domain – transport
N domain – ATP/ADP binding
P domain – phosphorylation
A domain – phosphatase activity
serca 1,2,3 ?
SERCA 1 striatal muscle
SERCA 2 smooth muscle, striatal muscle, heart muscle
– phospholambane
SERCA 3 platelets, endothelial cells and other non- muscle cells
pmca 1,2,3,4,5???
PMCA 1 general
PMCA 2 neuronal - higher affinity for cAMP phosphorylation
than PMCA 4
PMCA 3 striatal muscle, brain
PMCA 4 general
PMCA 5
alpha 1,2,3,4 in na k atpase
α1 - all tissues (heart also), kidney outer medulla only α1
α2 - striatal muscle, smooth muscle, heart (T-tubules)
brain (astrocytes)
adipocytes
α3 - brain (neurons)
heart (small amount)
ovary
leukocytes
α4 - testis
alpha 2»_space;»» alpha 3»» alpha 1»> senetivity to oubain
fxyd subunit
Tissue-specific regulator in the heart, kidney, pancreas, foetal liver
- 7.2 KDa (58 amino acids) – one transmembrane domain
- not an integral part of the enzyme
- different izoforms
Heart (FXYD1, phospholemman)
-when dephosphorylated it decreases the Na+ affinity of the α-subunit
-adrenergic β1 receptor stimulation → PKA stimulation →
phosphorylation of phospholemman → [Na+]i [Ca2+]i ↓ -prevention of
arrythmia
Kidney (FXYD2)
-increases the affinity of the enzyme for ATP
Kidney medulla is nearly anoxic under physiological conditions
- Some reabsorptions are under the control of the Na+-pump
- Moderate increase in the affinity for ATP → increased pump activity
(Fine tuning! Large affinity increase would cause further ATP ↓ !)
phosphorylation of C terminal loop on Na/K atpase
for some god damn reason Camp dependent phosphorylation inhibits it and PKC phosphorylation causes endocytosis of it. Way to get teaching dumb physiology.
aldosterone receptors alpha 1,2,3
long-term upregulation – isoform-specific
α1 – vascular smooth muscle
α2 – heart
α3 – brain
D1 and D2 receptors; phosphorylation by both PKA and PKC causes?
diuresis (loss of volume)
nhe antiport isoforms 1,2,3 locations.
5 isoforms - 12 transmembrane region
NHE 1 general (basolateral membrane)
NHE 3 epithelial cells apical membrane
NHE 5 brain, testis
Vesicular neurotransmitter antiporters (VMAT1, 2, VAChT) and inhibitor.
Proton antiporter (vesicular membrane antiporters, VMAT)
12 transmembrane segments
broad selectivity: epinephrine, norepinephrine,
dopamine, serotonin
VMAT1 brain, neuroendicrine cells
VMAT2 neurons, adrenal chromaffin cells
VAChT cholinergic synapses
Inhibited by H+ ionophores
abca1 and 3, abcb1, abcb4, abcc1, cftr
you suu good.
ABCA1 – cholesterol, phopholipid transport - reverse cholesterol transport
ABCA3 – translocation of pulmonary surfactant lipids
mutation: respiratory distress szindróma
ABCB1 (MDR1, multidrug resistence transporter)
- transport of lipophylic compounds – protection against toxins - increased expression in tumor cells: drug resistence
ABCB4 – canalicular membrane of hepatocytes
bile acid, phospholipid transport into the bile
ABCC1 (MRP-1, multidrug resistence protein)
- phospholipids, glutathione conjugates, anti-tumor drugs (also other
than lipophylic!)
CFTR (ABCC7, cystic fibrosis transmembrane conductance regulator)
Cl- flux in the apical membrane of epithelial cells
mutation: cystic fibrosis (thick mucus in the bronchi and pancreas
- blockage, infection, foetal ileus)
high affinity choline transporter uptake is inhibited by..
hemicholinium
inhibitor of vesicular acetylcholine transporter?
vesamicol
SNARE proteins in synaptic exocytosis
not synatpotagmin!!
In synaptic vesicles:
VAMP (vesicle-associated membrane protein) or synaptobrevin
In the plasma membrane:
Syntaxin 1A/B
SNAP-25 (synaptosomal-associated protein; 25 kD)
why shouldn’t I take botux?
Why should I know the chains it has?
Botulinum toxins
there’s 7 wonderful ways to kill myself.
7 neuro-toxin (BoNT- A,B,C,D,E,F,G) – inhibitors of the cholinergic neurotransmission
Light chain is the enzymatic part, heavy chain mediates uptake to the neuron.
It inhhibts release of the neuotransmitter.
don’t forget it is a Zn+ dependent endoprotease.
They love dem god damn Snare motifs.
If the person didn’t die from the botux he so willingly wanted, what should I give him (hint… it’s anti..)
heptavalent botulinum antitoxin
Ach muscarinic inhibitor,
Atropine.
If you got this wrong you killed at least 1 rabbit and 1 mouse (both simulated and a live one) for nothing.
-Topical atropine is used as a cycloplegic, to temporarily paralyze the accommodation reflex, and as a mydriatic, to dilate the pupils.
Ach Nicotinic inhibitor (It’s rhymes with cure, but not realy)
Curare
M1 muscarinic receptor
I added some receptors since it’s a nice revision.
– Gq – PLC-> PIP2 hydrolysis-> IP3-> Ca+ intracellular.
• Regulation of transmitter release
EPSP in autonomic ganglia[citation needed]
Secretion of catecholamines from the adrenal medulla[6]
Secretion from salivary glands
Gastric acid secretion from stomach[7]
In CNS (memory?)[8]
Vagally-induced bronchoconstriction[7]
Mediating olfactory behaviors (e.g aggression, mating) [9]
M2 muscurinic
heart Gi ↓ K+ channel activation ↓ Hyperpolarization ↓ Bradycardia
M3 muscurinic
Gastro-intestinal tract, Gq – [Ca2+]
– Smooth muscle contraction
– Secretion stimulation
it typically causes constriction of smooth muscle, such as that observed during bronchoconstriction. However, with respect to vasculature, activation of M3 on vascular endothelial cells causes increased synthesis of nitric oxide, which diffuses to adjacent vascular smooth muscle cells and causes their relaxation and vasodilation,
nicotinic receptor sunbunits
made up of 5 subunits, each one is 4 transmemb domain.
ligand binding, na+k+ (not selective) influx or efflux, depends on time bound on the receptor.
adult Ach muscle type subunits and his baby
baby / embryo- alph1, beta1, gama, delta (2:1:1:1:)
Adult- alpha 1, beta1, gama, epsilon (2:1:1:1)
specific inhibitor muscular type of nicotinic receptors
alpha-bundarotoxin.
binds to alpha subunit of nicotinic receptor (competitive inhibitor).
muscule paralysis.
malignant hyperthermia??
Malignant hyperthermia (rare complication during inhalation anaesthesia) Mutation of the Ryanodin receptors Altered kinetics of Ca2+ channels Persistent large increase in [Ca+ ]i Hypermetabolism Persistent activation of the contractile system Fever and Muscle rigidity
