week 10 Flashcards
Once Glucose is converted to Glucose-6-P (trapped glucose) it can
enter several pathways? what are they
Glycolysis
Pentose Phosphate Shunt
Glycogenesis
Which enzyme is needed to commit glucose-6-P to
glycolysis? (key controlling enzyme)
PFK1
The enzymes of the three irreversible reactions are
also the main regulated enzymes of glycolysis
PFK1
hexokinase/ glucokinase
pyruvate kinase
What reaction does Hexokinase catalyze?
- glucose - glucose 6 phosphate
- Reversibly regulated by glucose-6-phosphate
product inhibition
it is sensitive to need for glucose
When cellular concentrations of glucose-6-P rise above normal, what happens to hexokinase
it is temporarily inhibited to bring rate of glucose 6 P into balance with its rate of utilization
…. inhibits PFK1 by binding to an allosteric site. This lowers …… and …. and …. relieve the inhibition of PFK-1
ATP
Lowers the affinity of the enzyme for fructose-6-P
AMP and ADP relieve the inhibition of PFK-1
…. is a key intermediate in CAC . High levels of …… inhibit PKF-1.
citrate
citrate
Fructose 2,6-bisphosphate is the ……….. and activates …… it also enhances the affinity of ….. for …. stimulating glycolysis. Then inhibits ….. slowing gluconeogenisis
allosteric regulator
PFK-1
PFK-1 for fructose -6 -P
FBP-1
Fructose 2,6-bisphosphate is formed by phosphorylating ……….. by …..
Fructose-6-P, catalyzed by phosphofructokinase-2 (PFK-2)
What reaction does pyruvate kinase catalyze
the direct transfer of phosphate from phosphoenolpyruvate (PEP) to ADP to produce ATP and pyruvat
Pyruvate kinase is allosterically regulated by:
inhibition:
1. ATP
2. Acetyl-CoA
3. Fatty acids
Activation :
Fructose 1,6-bisphosphate
Glycolysis is regulated
hormonally by
insulin and
glucagon
insulin promotes the
transcription of (3)
Insulin also
promotes the activation of
Hexokinase,
phosphofructokinase-1, and
pyruvate kinase
PFK- 1 ( & inhibition FBP-2)
Glucagon reduces the expression of (3)
hexokinase, PFK-1, and pyruvate kinase
Glucagon promotes the
activation of
FBP-2 (& inhibition
PFK-2)
Fructose, Mannose, and galactose are converted into
glycolytic intermediates
Fructose metabolism primarily occurs in the
liver
Which monosaccharide is metabolized faster,
glucose or fructose, why?
glucose because it is absorbed by alot of cells in the body, where as fructose is not so it undergoes additional steps in the liver
The first two bypass reactions are the main
regulated reactions of gluconeogenesis
What were these bypass reactions?
Pyruvate Carboxylase (Bypass of Pyruvate Kinase)
Phosphoenolpyruvate Carboxykinase (PEPCK) (Bypass of Pyruvate Kinase):
Pyruvate can be converted either to:
acetyl CoA –> enter into CAC
Oxaloacetate —> enter into GNG
Lactate (Cori cycle)
What enzyme catalyzes conversion of pyruvate to oxaloacetate
pyruvate carboxylase
what is a allosteric activator of pyruvate carboxylase?
Acetyl CoA
What reaction does FBP-1 catalyze
catalyzes the hydrolysis of fructose-1,6-bisphosphate (FBP) to form fructose-6-phosphate and inorganic phosphate (Pi).
This reaction is a key regulatory step in both gluconeogenesis and glycolysis pathways.
what does F26BP inhibit and stimulate (fructose 2,6 bisphosphate)
inhibits glycolysis and stimulates gluconeogensis
Gluconeogenesis is regulated hormonally by
insulin and glucagon
Glucagon promotes activation of ….., lowering levels of ……….
FBP-2
fructose 2,6 bisP
Glucagon can also induce the transcription of
PEP carboxykinase
what is this pentose phosphate shunt? what is its purpose?
Alternative metabolic pathway for glucose that
“shunts” molecules into and out of glycolysis
purpose:
Generates two main products:
- NADPH
- Ribose-5-Phosphate (“pentose phosphates)
Also generates Fructose-6-Phosphate and glyceraldehyde3-Phosphate, which can feed back into glycolysis
where does the pentose phosphate shunt happen
cytoplasm
why is it called a shunt?
“shunts” or diverts some of the glucose-6-phosphate away from the usual glycolytic pathway, where it would continue to be metabolized to produce ATP through glycolysis. Instead, the glucose-6-phosphate is directed into the PPP to serve different purposes, such as generating NADPH or ribose-5-phosphate.
what are the two phases of the pentose phosphate shunt
oxidative (irreversible) and non oxidative(reversible)
describe the oxidative phase of the pentose phosphate shunt. what are its functions?
Glucose-6-phosphate -> Ribulose-5-Phosphate
generates 2 NADPH
functions:
- fatty acid synthesis
- reduces glutathione
what is glutathione? what role does NADPH play with glutathione?
a 3 amino acid peptide (glycine-cystine glutamate)
- neutralizes and reduces hydrogen peroxide to water by donating electrons
- NADPH regenerates glutathione by replacing the donated Hs
what is the oxidative phase regulation in PPP
Rate-limiting step:
Glucose-6-P –> 6-phosphoglucono-�-lactone
Enzyme: glucose-6-Phosphate dehydrogenase (G6PD)
Regulated by ratio of NADPH:NADP+
inhibited by high levels of Acyl CoAs
upregulated by insulin
High NADPH:NADP+ ratio inhibits
G6PD
G6PD deficiency is an …..linked trait and results in …..
X
Results in hemolytic anemia when an individual is
exposed to oxidant stress
in the non oxidative phase of the PPP …
Riboluse-5-P is converted to
Ribose-5-P OR into
glycolytic intermediates
Glucose is stored in polymeric form as glycogen
mostly in the
liver and skeletal muscle
High glucose/energy levels will triggers
glycogen synthesis (glycogensis)
Glucose can be rapidly delivered to the blood
stream when needed by
degradation of glycogen in
the liver
- Glycogenolysis
Glucose is transferred onto a growing chain of glycogen as
UDP-glucose
UDP-glucose is added to an existing strand of
glycogen by the enzyme
glycogen synthase
Glucose is added to the
non-reducing end in what
type of link?
glycosidic linkage
Branching enzyme catalyzes the transfer of ……. to ……
4-8 glucose residues to a branch point
Branching enzyme is also called amylo-α(1,4 —–> 1,6)
glucosyl transferase
Glycogen synthase cannot initiate a new glycogen
chain de novo, it requires a primer. what does the primer contain?
pre-formed (alpha1 —> 4) polyglucose chain with at least 4-8 glucose residues
- Found within glycogenin (contains both the enzyme and the primer to create the primer)
in glycogenolysis …… is removed from ….. ends of glycogen by enzyme …. Sequentially cleaves Sequentially cleaves ……..from the non-reducing
ends until ……units away from a branch point. Then glucose is released as ….. Once all chains degraded to
within 4 units of a branch point, the molecule is called a …..
non reducing
glucose
glycogen phosphorylase
α (1 –> 4) linkages
4
Glucose is released as
glucose-1-P
limit dextrin
the glycogenolysis de-branching enzyme has
two functions:
- transfers the outer 3 glucose
residues from the branch to
another non-reducing end
(leaving only 1 reside behind at the branch point)
* Aka Oligo-α(1,4)-α(1,4)-
glucotransferase - Removes the final glucose
residue in the alpha(1–> 6) linkage
* Aka Amylo-α(1,6) glucosidase
in glycogenolysis Glucose-1-P is converted to ….. by enzyme ….
glucose-6-P
phosphoglucomutase
The liver can then convert glucose-6-P into glucose
with the enzyme …..
Glucose-6-Phosphatase (G6Pase)
what muscles do not have Glucose-6-Phosphatase (G6Pase)
Muscles, on the other hand, do not release glucose into the bloodstream as a primary function. Instead, muscles use G6P for their own energy needs and store it as glycogen.
what are the two regulated enzymes in glycogen metabolism
Glycogen synthase
glycogen phosphorylase
Glycogen synthase regulation is Allosterically activated by
glucose-6-P
Glycogen phosphorylase regulation is Allosterically inhibited by:
Glucose-6-P
* ATP
* Free glucose (in the liver only)
- Allosterically activated by AMP (muscle only)
Glycogen synthase and glycogen phosphorylase can
also be regulated by
covalent modification
Glycogen synthase is de-activated by
phosphorylation
Glycogen phosphorylase is activated by
phosphorylation
Phosphorylation is catalyzed initially by the same protein,
protein kinase A (PKA)
How is PKA activated?
system involving cyclic AMP
Covalent modification of glycogen
metabolism is under
hormonal control
In the presence of glucagon (and
epinephrine):
Glucagon binds to its GCPR
* G⍺s activates adenylyl cyclase —>
cAMP levels rise
* PKA phosphorylates glycogen synthase, rendering it INACTIVE
- Glycogenesis is inhibited
- PKA phosphorylates
glycogen phosphorylase
kinase, rendering it
ACTIVE - Glycogen phosphorylase
kinase phosphorylates
glycogen phosphorylase,
rendering it ACTIVE - Glycogenolysis is
promoted
glycogen metabolism In the presence of Insulin
- Insulin promotes the breakdown
of cAMP and thus inactivation of PKA - Insulin activates protein
phosphatase 1, which removes the phosphate group from glycogen synthase, rendering it ACTIVE
glycogenesis is promoted
- Insulin promotes the
breakdown of cAMP and
thus inactivation of PKA - Insulin activates protein
phosphatase 1, which
removes the phosphate
group from: - Glycogen
phosphorylase
kinase & Glycogen
phosphorylase,
rendering them both
INACTIVE - Glycogenolysis is inhibited
somatic sensory, non cranial
touch, pain, pressure , vibration, temperature
spinal nerves
TO spinal cord
somatic motor non cranial
non cranial skeletal muscles
FROM spinal cord
spinal nerves
visceral motor
autonomic NS all the SNS and sacral PaNS
Spinal nerves
FROM spinal cord
somatic motor cranial
cranial skeletal muscles
cranial nerves
visceral motor
parasympathetic nervous system
cranial nerves
white matter
collections of mylienated axons in the CNS
mylien is
a multi layer lipid coat that insulates axons formed by specialized glial in the peripheral and CNS
increases conduction velocity
only ….. has white matter
CNS
grey matter is
areas of the central nervous system that have relatively few myelinated axons
tract
a collection of axons in the CNS
large tracts are usually white matter
a nerve is a
collection of grey matter in the PNS
what are the sites of integration of the neuron
cell body and axon hillock
dorsal columns in the spinal cord are examples of
tracts
much of the volume of the cerebral cortex is ……
……. forms a relatively thin layer superficially
white
grey
How does the peripheral nervous
system (PNS) differ from the central
nervous system (CNS)?
Different cells populate the PNS
Axons/nerves in the PNS can
sometimes regenerate after damage
The PNS is much less “isolated” than
the CNS – cells of the immune system
are allowed to enter and exit the PNS
more freely
Fewer neuronal cell bodies in the PNS
versus the CNS
Ganglia
collections of neuronal cell
bodies in the peripheral nervous system
Nuclei
collections of neuronal cell
bodies in the central nervous system
basal nuclei are often known as
basal ganglia – widely accepted
misnomer
Both nuclei and ganglia will contain
axons, but more of the volume of these
structures is devoted to
neuronal and
glial cell bodies
Glial cell types:
Astrocytes
Oligodendrocytes
Microglia
Fluid spaces within the CNS
Ventricles, ependymal cells, choroid plexus, Interstitial fluid
functions of the astrocyte
forms a part of the blood brain barrier
regulates interstitial fluid composition
provides structural support and organization to the central nervous system
assists with neuronal development
replicates to occupy space of dying neurons
functions of the ependymal cell
lines ventricles of brain and central canal of spinal cord
assists in production and circulation of cerebrospinal fluid
functions of microglial
phagocytic cells that move through the CNS
protects the CNS by engulfing infectious agents and other potential harmful substances
functions of the oligodendrocyte
myelinated and insulates axons
allows faster action potential propagation along axons in the CNS
what are the most numeral cells in the CNS
astrocytes
- highest in grey matter
what is the critical role of astrocytes in the CNS
Facilitate the formation and strengthening of synapses (neuroplasticity)
Regulate the concentration of ions in the interstitial fluid
* K+, Na+, Cl-, HCO3-, Ca+2
Structural support for the brain
* Intermediate filament – GFAP (glial fibrillary acidic protein)
Barrier functions – induce the formation of the BBB at the brain microvasculature, form a “limiting membrane” at the external CNS surface
“Feed” neurons – help extract nutrients from the blood, provide nutrients to neurons to support energy metabolism
astrocytes are connected to eachother via
gap junctions
Small “tunnels” that connect the
intracellular fluid of astrocytes to
each other (span the cell
membranes and connect cell to
cell) in a network known as a
syncytium
waves” of calcium increases
and general ……that
move through the brain,
astrocyte-to-astrocyte have been observed
depolarization
what are the processes of oligodendrocytes
Each process wraps around the axon of
a CNS neuron many times, “sheathing”
the axon in myelin
Myelin sheath = compacted layers of
cell membrane rich in sphingolipids
that have very little cytosol
what is the function of mylien
Increases the speed with which an
action potential moves down an axon
Reduces the energy consumed by
movement of an action potential down
an axon – more efficient signaling
roughly …. as many oligodendrocytes as neurons in the CNS
twice
what are the functions of microglial cells
Remove (phagocytosis) cellular debris
Monitor the environment and fight pathogens
If the pathogen cannot be eliminated by resident
microglia, they “call in” other white blood cells through secretion of soluble factors (cytokines) and can present antigen to other immune cells
what are microglial cells derived from?
blood borne immune cells that migrate into the CNS
subarachnoid space
Around the periphery of the brain
where is the cerebrospinal fluid found
subarachnoid space
Within particular compartments
of the brain (4 ventricles - third ventricle, lateral ventricle, 4th ventricle and cistern)
where does the CSF circulate
moves from lateral ventricles to 3rd then 4th ventricles
circulated into the subarachnoid space and down the spinal cord
eventually absorbed by specialized structures known as arachnoid granulations (transport CSF into venous structures)
where is the CSF formed from?
choroid plexus (a complex of capillaries and epithelial cells)
the choroid plexus …
Selectively transports water, electrolytes,
nutrients from blood to CSF
Tight junctions prevent unwanted substances
from entering the CSF
The interstitial fluid (extracellular fluid) of the brain and spinal cord is formed by
Filtration of CSF from the ventricles through
the ependymal cells
Regulated filtration of fluid through capillaries
deeper in the CNS tissue
The central nervous system is
isolated/protected from a number of
factors that can circulate through the
bloodstream such as
Immune cells
* White blood cells attack pathogens and
remove cellular debris
* The CNS structure is delicate, and its
function depends on its precise architecture – usually white blood cells aren’t allowed into the CNS
Exception – microglial cells
Noxious wastes and toxins
Pathogens
Most capillaries in the body are quite …. they have few…
leaky
Nutrients, electrolytes, water,
metabolites filter through easily – few
tight junctions
Astrocytes contact capillaries in the CSF
via structures known as
endfeet
Endfeet cause
increased tight junction
expression in capillary endothelial cells
Endfeet also “tell” capillaries what to
transport into the CNS tissue
what are the three structures in a nerve
Epineurium
Perineurium
Endoneurium
what is the epineurium
strong, fibrous connective tissue covering that surrounds each nerve
Blood vessels run within this layer – known as the vasa
nervorum
what is the perineurium
surrounds bundles of axons (some myelinated, some not) known as fascicles
formed by fibroblast-like cells arranged in
sheets 2-6 cells thick
Tight junctions are found between these cells – therefore the
perineural layer can regulate what moves into the fascicle
what is the Endoneurium
delicate connective tissue layer that surrounds individual axons
what is in barrier 1 of the BNB
the cells of the perineurium and the tight junctions between them
what is in barrier 2 of the BNB
the endothelial cells that line the capillaries
within the fascicles also express many tight junctions
what do both BNB actively regulate
movement of ions
and immune cells into the fascicles
which is more permissive to the entrance of white blood cells? BNB or BBB?
BNB
Schwann cells
provide the myelin
sheath for axons
within fascicles
how do schwann cells differ from oligodendrocytes
in that one cell only
myelinates one axon
- Each oligodendrocyte
myelinates multiple
nearby axons - Schwann cells can
extend as far as 1
mm along an axon
Satellite cells surround,
protect, and nourish
neuronal cell bodies located
in ganglia
- do not establish blood ganglion barrier
Multiple satellite cells are closely apposed to
neuronal
cell bodies
The morphologic relationship of the dendritic spine to
the axon terminal can influence the
effectiveness of the
synapse
Spine maturation makes the synapse more
effective
what is the flopodia
dendritic spine immature and
“looking for a connection” with an axon terminal
The “mushroom” and “branched” spines were shown to elicit
more effective neuronal responses when they are stimulated
the soma is a
Site of protein synthesis for the rest of the neuron
Nissl substance
basophilic area nearby the nucleus of a neuron composed of lots of free ribosomes and rER
Microtubules, actin microfilaments, and
neurofilaments found in the body and in the
processes of neurons
Neurofilaments =
intermediate filaments that are
more concentrated in axons – provide structural
stability for neuronal processes
Microtubules have
opposite orientation in dendrites
vs. axons – this is arranged in the cell body
Pseudo-unipolar neurons
These neurons have a distal process that
either interacts with a sensory receptor or
serves as a sensory receptor (A)
The proximal process synapses in the CNS
(B)
The process that connects A to B behaves
as an axon
Typical of dorsal root ganglion cells –
somatic sensation
Bipolar neurons
These neurons have a distal process (A)
that acts as a dendrite – it either serves as
a sensory receptor or interacts with a
sensory receptor
The proximal process synapses in the CNS
– it is an axon and conducts action
potentials (B)
Typical of neurons that detect the special
senses – vision, hearing, smell
Multipolar neurons
The most common neurons
Dendrites receive information from
other neurons via synaptic terminals
The cell body summates and
integrates this information
The axon carries action potentials to:
- Other neurons
- Glands
- Muscle tissue
Typical of all interneurons and
somatic motor neurons
Cranial nerve afferents:
Special Senses
* CN I, II, VII, VIII, IX, X
* Somatic Senses
* Mostly CN V
Visceral Sensory
CN IX and X
* Baroreceptors
* Visceral sensation
from most of the
alimentary tract,
lungs, heart
Sensation is composed of a number of distinct steps
(not all need to be present):
Detection of a physical/chemical stimulus by some type of
receptor
Transduction – transforming the physical stimulus into an
electrical impulse that can be carried along an axon
Other neurons at various levels of the central nervous system can detect the electrical impulse and modify its intensity and route the signal to various CNS locations
Perception – conscious awareness of the sensation – this occurs at the level of the cortex
Afferents that ascend through the spinal cord:
Somatic sensation below the neck
Visceral Sensation
Examples of effectors
- Skeletal muscle (voluntary movements)
- Smooth muscle (blood vessels, GI tract,
genitourinary tract, respiratory tract) - Glands (endocrine or exocrine)
Somatic Motor
efferents
control of skeletal muscles
- Usually voluntary
- Some we don’t have conscious control over (i.e.
middle ear muscles)
Major cranial nerves –
somatic motor:
- CN VII, V, XI
- CN IX, X, XII
- CN III, IV, VI
Efferents for skeletal
muscles below the neck
are part of the
corticospinal tract
Axons from neurons in
the pre-central gyrus
decussate and descend
down the spinal cord
Synapse on anterior
horn motor neuron
Axon of anterior horn
motor neuron exits the
central nervous system
as a spinal nerve
Visceral motor
efferents – cranial
nerve PaNS
CN X – PaNS control
for the heart, lungs,
majority of the GI
system
CN III – PaNS
control over
pupillary muscles
CN VII, IX – PaNS
control over
salivary, tear glands
Visceral motor
efferents – spinal
nerve ANS & PaNS
SNS control for the
heart, lungs,
proximal GI tract
SNS control for
pupillary muscles,
salivary glands, tear
glands
SNS and PaNS
control for distal GI
tract, reproductive
structures, bladder
Sympathetic Nervous System
“Fight or Flight”
- Increases heart rate and cardiac output
- improves ventilation
- Decreases digestive function
- Increases glucose availability (gluconeogenesis,
glycogenolysis)
- Increases blood flow to skeletal muscles, heart
- Decreases blood flow to GI tract, skin, kidneys
- Major hormones/neurotransmitters: epinephrine and
norepinephrine
paravertebral ganglia
adjacent to the vertebral column
prevertebral ganglia
Anterior to vertebral
column
Parasympathetic Nervous System
Rest and digest
- Decreases heart rate and cardiac output
- Bronchoconstriction and increased mucous secretion
- Increases digestive function and GI motility
- Increases blood flow to digestive tract
what is the major neurotransmitter in the parasympathetic NS
acetylcholine
what are the two paths of the PaNS
Vagus nerve – all of
the visceral
efferents up to the
proximal large bowel
Sacral nerves – all of
the visceral
efferents to the rest
of the large bowel,
kidney, reproductive
organs
Ganglia are located
closer to target
organs
