BECOM Exam #2 Flashcards
Sympathetic Branch: Stimulation
Pupil dilation (mydriasis) Dry mouth Sweat production Increased heart rate & force of contraction Bronchiole dilation Fuel mobilization (glucose, lipolysis) Blood vessel constriction Increase blood pressure Exercise increased metabolism in skeletal muscle which over-rides this effect and dilates to allow blood flow to increase Gut constrict Coagulation Ejaculation/orgasm
Parasympathetic Branch: Actions
Constricts pupils and bronchioles
Slows heart rate & force of contraction
Stimulates
Digestion
Salivation
Insulin release
Urination
Erections (arousal)
S.L.U.D.G.E.(M) ->extreme parasympathetic stimulation
Organophosphate poisoning
Salivation, lacrimation, urination, defecation, gastrointestinal, emesis, muscle spasm/miosis (pinpoint pupil)
Intracrine
signals are produced by the target cell that stay within the target cell. Example: secondary messengers
Autocrine
signals are produced by the target cell, are secreted, and affect the target cell itself or a near by cell of the same type via a receptor. An example of this are immune cells.
Paracrine
signals target cells in the vicinity of the emitting cell. E.g. neurotransmitters.
Endocrine
signals target distant cells. Endocrine cells produce hormones that travel through bloodstream to reach all parts of the body. E.g. hormones
Juxtacrine
signals target adjacent (touching) cells. These signals are transmitted along cell membranes via protein or lipid components integral to the membrane and are capable of affecting either the emitting cell or cells immediately adjacent. E.g. gap (tight junctions, notch signaling, etc).
Receptor Tyrosine Kinases Regulate what?
Cell proliferation, growth, differentiation, migration
GEF
GDP –> GTP
GAP
speed up GTP hydrolysis
Adenylyl Cyclase
ATP makes 5’-AMP -> cAMP
phosphodiesterase
cAMP –> 5’-AMP
What occurs when GDP goes to GTP (amino acids)
Thr and Gly residues are pulled to the third phosphate making a conformational change
Ras MAP Kinase Pathway causes
cell proliferation
Signaling issues that promote cancer
- RTK: becomes dimerized and phosphorylated with out ligand bound
- Overexpression: large amount of kinases in the membrane
- Activating mutation: produce a product that mimics phosphorylation or conformational change of kinase
HER2
RTK that are over expressed that cause cell proliferation. antibody bind to HER2 receptor causing no dimerization
NF-kB
- TNF activates NF-kB
- alphaB is phosphorylated and disassociates with NF-kB allowing NF-kB to translocate into the nucleus and act as a transcription factor
- leads to pro-inflammatory signals
- rheumatory arthritis
Humira
- is a monoclonal antibody that binds to TNFalpha not allowing it to bind to TNFR (RTK)
- lowers immune response
Enbrel
receptor that binds to TNFalpha with no signal (essentially an inhibitor to the cascade)
Philadephia Protein
- translocation of chromosome 9 and 22
- chromosome 22 shorter than normal
- Bcr-Abl protein
Graded Potential
- starts above threshold at is initiation point but decreases in strength as it travels through the cell body
- if not a threshold at trigger point -> no action potential
- summation
Action Potential
- A regenerating depolarization of membrane potential that propagates along an excitable membrane
- at trigger zone (all or nothing)
- only uses K+/Na+ channels
- no summation
speed of transmission depends on
- fiber size
- myelinated
- resistance
refractory period
is defined from the time the activation/inactivation gates begin moving, until they are “re-set” (activation gate closed / inactivation gate open) to their original configuration at resting membrane potential
Absolute refractory period
AP will not fire, irrespective of stimulus intensity.
Relative refractory period
- stronger than normal stimulus may elicit an AP.
- Note: As relative refractory period progresses, the level of excitability increases.
- action potential will take more time because not as many fast Na+ channels in ready state
greater than normal stimulus effect on amplitude of AP
- no effect on amplitude but will have a greater than normal frequency of AP firing
- rate of frequency is how AP is graded
- greater release of neurotransmitter
Postsynaptic receptor proteins bind to receptors (binding component) and then either
- Alter chemically gated ion channel (open or close)
- EPSP (excitatory)
- IPSP (inhibitory) - Activate 2nd messenger systems
- Open specific ion channels on the postsynaptic membrane
- Activation of cAMP or cGMP
- Activation of one or more intracellular enzymes
- Activation of gene transcription
Postsynaptic receptor proteins activate 2nd messenger systems
- Open specific ion channels on the postsynaptic membrane
- Activation of cAMP or cGMP
- Activation of one or more intracellular enzymes
- Activation of gene transcription
Neurotransmitter inhibitors
- g-aminobutyric Acid (GABA)
- Glycine
-hyperpolarize the cell
Tyrosine Hydroxylase (TH)
tyrosine -> L-Dopa -> Dopamine
Dopamine B hydroxylase (DBH)
Dopamine -> Norepinephrine
phenylthanolamine-N-methyltransferase (PNMT)
Norepinephrine -> Epinephrine
VMA
Breakdown of norepinephrine and epinephrine
HMA
breakdown of dopamine
Monoamine Oxidase (MAO)
breaks down 5HT in serotonin synapse
Monoamine Oxidase (MAO)
- breaks down 5HT in serotonin synapse
- Norepinephrine
Inactivation of Neurotransmitters
glial cells
blood vessels
enzymes
Choline acetyltransferase
catalyzes the transfer of an acetyl group from the coenzyme acetyl-CoA to choline, yielding acetylcholine
Post-synaptic cholinergic receptors
- Muscarinic
- Nicotinic
acetylecholine esterase
acetylcholine -> acetate + choline
Spatial Summation
total surface area that inputs are taking up on a neuron
Temporal Summation
The net sum of inputs per unit of time on the presynaptic neuron determine the level of excitability
Presynaptic vs postsynaptic inhibition
Presynaptic: 2/3 synapses release neurotransmitter
Postsynaptic: 0/3 synapses release neurotransmitter
Synaptic Transmission Fatigue
- exhaustion of the stores of transmitter in synaptic terminals
- excitatory synapses are repetitively stimulated at a rapid rate until rate of postsynaptic discharge becomes progressively less.
- development of fatigue is a protective mechanism against excessive neuronal activity (seizures)
Synaptic Transmission Fatigue
- exhaustion of the stores of transmitter in synaptic terminals
- excitatory synapses are repetitively stimulated at a rapid rate until rate of postsynaptic discharge becomes progressively less.
- development of fatigue is a protective mechanism against excessive neuronal activity (seizures)
Acidosis effect on excitability/inhibition
H+ accumulates extracellularly -> Less Na+ in (exchanged for H+) -> tends to hyperpolarize and depress excitability.
Alkalosis effect on excitability/inhibition
less H+ extracellularly -> drives exchange -> more Na+ in -> increases excitability through depolarization effect.
hypoxia effect on excitability/inhibition
- Initial (very short) excitation
- Reduced O2 availability prolonged No ATP for pumps
Post-tetanic facilitation
- enhanced responsiveness following repetitive stimulation.
- mechanism thought to be build-up of calcium ions in the presynaptic terminals.
- build-up of calcium causes more vesicular release of transmitter.
Synaptic delay
-0.5 ms in mammals
Sympathetic
“Fight or flight”
Energetic action
Mobilization of energy to fight or flee
Parasympathetic
“Rest and digest”
Restore body function
Decreased metabolism, favors energy storage
Medulla controls
- Respiration
- Cardiac, vascular, visceral
Pons
Respiration, urinary
Hypothalamus
Body fulid balance, temperature, and hunger
Sympathetic Innervation Only (non-dually innervated
- Arteriolar smooth muscle – blood pressure
- Kidney – body fluid balance and blood pressure
- Sweat glands
- Adipose (lipolysis)
- Clotting
Somatic neural pathway
motorneuron -> Nicotinic 2 on skeletal muscle
Autonomic Neuron Structure & Synapse
- Varicosities
- large area, slow acting
- no synaptic cleft
- released into extracellular fluid
Alpha 1
- Smooth muscle contraction
- NE>EPI
Alpha 2
- Also presynaptic inhibition of NE release
- NE>EPI
Beta 1
- Cardiac, renin release from kidney, lipolysis
- NE=EPI
Beta 2
- Smooth muscle relaxation
- EPI»NE
Beta 3
- Thermogenesis from brown adipose tissue
- NE>EPI
Sympathetic Branch Inhibition
Increased digestion Pancreas secretion Urination Slow heart rate Reduce blood pressure
Sympathetic spinal seg
thoracolumbar (T1-L3)
Parasympathetic spinal seg
cranial and sacral divisions
Sympathetic neural pathway
- preganglionic (ACh) -> Nicotinic 2 receptor on postganglionic (NE) -> alpha 1/2, beta 1,2,3
- smooth muscle, glands, cardiac muscle
- postganglionic (ACh) -> Muscarinic
- sweat glands
Parasympathetic neural pathway
- preganglionic (ACh) -> Nicotinic 2 receptor on postganglionic (ACh) -> Muscarinic
- smooth muscle, glands, cardiac muscle
Adrenal Medulla neural pathway
-preganglionic (ACh) -> Nicotinic 2 receptor on adrenal medulla -> to circulation (80% EPI, 20% NORE)
Parasympathetic Branch Inhibition
Inhibit digestion
Reduces secretory functions (dry mouth)
Increases heart rate
Vagus nerve stimulates
- parasympathetic
- Heart
- Lungs
- Intestines
- Stomach
bradycardia
slow HR
diaphoresis
sweaty
hypertension
high blood pressure
blood pressure is mainly controlled by
sympathetic nerves system
Low dose EPI
blood pressure decreases
High dose EPI
blood pressure increases
Heart Beta stimulation
Increased HR
Bronchiole smooth muscle Beta stimulation
bronchodilation
Apla 1 signaling cascade
IP3, increase intracellular Ca2+
Apla 2 signaling cascade
inhibit adenylyl cyclase, decrease cAMP
Beta 1 signaling cascade
stimulate adenylyl cyclase, increase cAMP
Beta 2 signaling cascade
stimulate adenylyl cyclase, increase cAMP
Nicotinic signaling cascade
Opening Na+ and K+ channels, depolarization
Muscarinic signaling cascade
- IP3, increase intracellular Ca2+
- inhibit adenylyl cyclase, decrease cAMP
Alpha 1 target tissue
vascular smooth muscle
skin
gastric tract
bladder
Alpha 2 target tissue
gastrointestinal tract
beta 1 target tissue
heart
salivary glands
adipose tissue
kidney
beta 2 target tissue
vascular smooth muscle of skeletal muscle
gastrointestinal tract
bladder
bronchioles
tachycardia
increase HR
glycogenolysis
break down of glycogen
GLUT 2
- Liver and Pancreatic Beta cells
- will take in glucose for storage as glycogen when level of glucose are high
- high km for glucose
- Pancreatic Beta cells: when high glucose excretes insulin
GLUT 3
Brain
GLUT 4
- skeletal muscles and adipose
- insulin response and exercise
Leptin
stops hunger when glucose level are sufficient
S.L.U.D.G.E.(M)
Organophosphate poisoning
Salivation, lacrimation, urination, defecation, gastrointestinal, emesis, muscle spasm/miosis (pinpoint pupil)
Acetyl CoA carboxylase in fed and fasting state
unphosphorylated (active) in fed state
phosphorylated (inactive) in fasting state
TCA cycle occurs in the
mitochondrial matrix
Acetyl CoA comes from
Glycolysis, fatty acid b-oxidation (ketone bodies), amino acid breakdown
B3 (nicotinamide) makes up
NAD
NADH is produced where and used where
produced through TCA and used in Oxidative phosphorylation
Complex I reduces
NADH
Complex IV reduces O2
with 4 H+ to make H2O
Coenzyme Q (Ubiquinone) job
Small molecule electron shuttle in the mitochondrial
inner membrane
complex I is inhibited by
rotenone
barbituantes
MPP+
complex II is inhibited by
nitropropionic acid
malonate
complex III is inhibited by
antimycin A
complex IV is inhibited by
CN-, N3-, H2S, CO
Complex II oxidizes
succinate to fumarate
Most reactive ROS
.OH hydroxyl radical
ROS pathway
O2.- -> H2O2 -> OH- + OH. -> H2O
Fenton and Haber-Weiss reaction
Fe2+ and Cu1+ react with hydrogen peroxide and superoxide to form hydroxyl radicals
NOX 1
neutrophils releases H2O2 from its cell to affect bacteria
NOX 2
- neutrophils will release HOCl and OH- in the phagosome membrane to break down bacteria
- granulomas can form when this is defective
Nitric Oxide synthase constitutive form job
-iNOS1
-NO normally involved in vasorelaxation via
soluble guanylate cyclase
-make small “bursts” of ●NO in response to Ca2+ transients
Process of Nitric oxide formation form macrophage
202 + NADPH (enzyme NOS2) -> NO
How do ROS effect us?
- oxidize fatty acids
- oxidized fatty acid can diffuse out of cell and attack other parts
Antioxidants include
-Superoxide dismutase (SOD) accelerate O2•- ->H2O2
-Catalase (CAT, a Mn-containing enzyme) finishes detoxing H2O2
2 H2O2 O2 + 2 H2O
-Glutathione Peroxidase (GPx, Se dependent & independent)
GSH + H2O2 -> GSSG + H2O
How do Tocopherols (vitamin E) act
takes radical from hydroperoxal radical and allows to have the radical taken up
GSH as cellular reductant
- Acts with enzymes like glutathione peroxidase to remove peroxides ROOH
- comes from
what are antioxidant gene regulated by
Nrf2 disassociates from Keap
Cori Cycle
Heart & liver convert lactate back to pyruvate, liver converts pyruvate back to glucose (gluconeogenesis) or oxidizes it.
catapleurosis
- removal of intermediates from the Kreb cycle
- OAA -> asparagine/aspartate
anapleurosis
- replacement of kreb cycle intermediate “fill up”
- asparagine/aspartate -> OAA
Methyl malonic aciduria (MMA):
- Genetic deficiency of methyl malonyl CoA mutase or low B12
- methyl malonyl CoA -> succinyl CoA for TCA Cycle
pyruvate carboxylase
Pyruvate -> oxaloacetate
Pantothenic acid = Vitamin B5
CoA
carboxylase enzymes need
biotin (B7)
Thiamine (B1)
- pyruvate dehydrogenase and oxoglutarate dehydrogenase (also called α-ketoglutarate dehydrogenase)
- alc can damage uptake of thiamine
Lipoic acid
Cofactor of PDH and aKGDH
Riboflavin (vitamin B2)
- Bound cofactor of succinate dehydrogenase
- used by complex II of ETC
- part of FAD
Pyridoxal phosphate (vitamin B6)
- PLP enzyme
- B6 and B12 deficiencies in older individuals
beriberi and wernicke-korsakoff
thiamine deficiency
pelagra
niacin deficiency
Pyruvate kinase
- Brain, muscle, RBCs contain no allosteric site
- Liver: inhibited (ATP, alanine) activation (F 1,6 bisP)
- inactive when phosphorylated (high glucagon levels)
Conversion of glucose to 2 lactate generates how many ATP via?
2 ATP from substrate-level phosphorylation
Malate-OAA shuttle
malate (reduced carrier) -> OAA (oxidized carrier)
Glucokinase vs hexokinase
Glucokinase has higher km than hexokinase and is localized in the liver
Pyruvate dehydrogenase
- pyruvate -> acetyl CoA
- links glycolysis and TCA cycle
- Turned off when the energy level of the cell is high or oxygen is lacking
Cofactors of Pyruvate Dehydrogenase Complex
thiamine pyrophosphate (TPP) (B1)
lipoate (lipoamide) (octanoic acid)
flavin adenine dinucleotide (FAD) (B2)
nicotinamide adenine dinucleotide (NAD+) (B3)
coenzyme A (CoA) (B5)
Enzymes that regulate glycolysis
hexokinase
Phosphofuctokinas 1
pyruvate kinase (regulated only in liver)
PFK-2 vs. FBPase
-PFK-2: fructose 6-P -> fructose 2,6 bisphosphate
high insulin (high blood glucose)
-FBPase: fructose 2,6 bisphosphate -> fructose 6-P high glucagon (low blood glucose)
whats the point of gluconeogenesis
make glucose in the liver so that it can be excreted and raise low glucose levels
What effects will high and low Acetyl CoA levels have on Pyruvate dehydrogenase and pyruvate carboxylase
- high Acetyl CoA with inhibit PDH and activate PC so that glucose can be made for glycogen storage
- high acetyl CoA because a FAs so oxaloacetate can be used to make glucose
alc effect on gluconeogenesis
- increases the amount of NADH
- inc NADH causes pyruvate to lactate
- because lost of pyruvate gluconeogenesis can’t occur
glycogenesis
the buildup of glycogen
glycogen phosphorylase
breaks down glycogen by inserting phosphate to break alpha 1,4 chain
Von Gierke Disease
- deficiency in glucose 6-phosphatase
- glycogen storage disease, can’t break down glycogen
Alpha receptor prefers
NE>EPI
Beta receptor prefers
EPI>NE
Beta receptor signaling pathway
cAMP inc
Alpha receptor signaling pathway
DAG + PIP2
Tumor in adrenal medulla secretes large amounts of
epinephrine
2nd Messenger Postsynaptic Effects
- Open specific ion channels on the postsynaptic membrane
- Activation of cAMP or cGMP
- Activation of one or more intracellular enzymes
- Activation of gene transcription
muscarinic vs beta 1 receptors
- heart rate
- muscarinic: inhibit AC, open K+ channels (hyperpolarization)
- beta 1: activates AC -> inc cAMP, open Na+ channels (depolarization)
major cellular reducing agent
NADH, NADPH, and GSH
Nitric Oxide synthase Inducible isoform
- NOS2
- in macrophages and microglia (brain macrophages)
- iNOS is upregulated in response to inflammogens, makes ●NO constantly so long as the protein and its cofactors (esp. tetrahydro-biopterin) are present and functional
mydriasis
dilation of pupils
normal glucose levels
70-80
C peptide
- used in the synthesis of insulin
- if individual doesn’t produce insulin then C peptide level will be low
