Ch 46 Metabolism of the Nervous System Flashcards
1
Q
What is the role of dendrites on a neuron? Axons?
A
The role of dendrites on a neuron is to receive information from the axons of other neurons.
The role of axons is to transmit information to other neurons.
2
Q
How many axons does a nerve have? Dendrites?
A
Neurons contain ONE axon, but these branch extensively and distribute information to multiple targets (divergence)
Neurons contain many dendrites, each receiving signals from multiple axons.
3
Q
What must a dendrite have to respond to a specific neurotransmitter?
A
specific receptor
4
Q
How does a neuron send a signal to multiple cells?
A
extensive axonal branching to multiple targets
5
Q
What stage of differentiation are neurons in?
A
terminally differentiated
6
Q
can neurons divide?
A
no, terminally differentiated
7
Q
What happens when a neuron is damaged?
A
Neurons that are injured or damaged have a limited capacity to repair themselves and frequently undergo apoptosis.
8
Q
What is the role of astrocytes in the CNS?
A
provide physical and nutritional support for neurons
Phagocytosing debris left behind by cells,
Providing lactate (from glucose metabolism) as a carbon source for the neurons, and
Controlling the brain extracellular ionic environment.
Regulate the content of ECF by taking up, processing and metabolizing nutrients and waste products
9
Q
What role do astrocytes play in development of the CNS?
A
guide neuronal migration to their final adult position and form a matrix that keeps neurons in place
10
Q
Where are oligodendrocytes located and what is their major role? List 3 additional roles.
A
oligodendrocytes are found in the CNS where they provide myelin sheath that surrounds the axon, which insulates many neurons in CNS.
(along with astrocytes) Form a supporting matrix for neurons
Limited capacity for mitosis, so if damaged it will not replicate
Note: It can result in abnormalities in signal conduction along that axon
11
Q
Where on the neuron is myelin? What cells produce myelin in the CNS? PNS?
A
The myelin is found around axons in both the CNS and PNS. The difference is myelin is produced by Oligodendrocytes in the CNS and Schwann cells in the PNS.
12
Q
Can oligodendrocytes divide?
A
no
13
Q
Name 2 cell types that provide a supporting matrix for neurons in the CNS
A
oligodendrocytes and astrocytes
14
Q
do damaged oligodendrocytes replicate?
A
no; They have limited capacity for mitosis and if damaged do not replicate.
15
Q
If oligodendrocytes are damaged, what may happen to neurons?
A
demyelination of the axons which can result in abnormalities in signal conduction along the axon
16
Q
How many axons can oligodendrocytes myelinate? Schwann cells?
A
Oligodendrocytes can myelinate multiple axons while Schwann cells myelinate only one axon.
17
Q
If a peripheral neuron’s axon is damaged, can it be regenerated?
A
yes
18
Q
Which brain cells serve an immunological function?
A
Microglial cells serve as immunologically responsive cells. They destroy invading microorganisms and phagocytose cellular debris.
19
Q
What type of cells do the microglial cells resemble in circulation?
A
macrophages
20
Q
Which cells in the brain have cilia? What are the cilia for?
A
Ependymal cells are ciliated cells that line the ventricles of the CNS and the spinal cord. The cilia are for efficient circulation of the CSF throughout the CNS.
Note: in some areas of the brain, they elaborate and secrete CSF into the ventricular system
21
Q
Where are ciliated cells located?
A
line the cavities (ventricles) of the CNS and spinal cord
22
Q
Some of the ciliated cells can produce ____
A
CSF
23
Q
What type of stem cells has recently been found within the ependymal cell layer?
A
neural stem cells
24
Q
Name the cell types of the CNS and PNS that can perform phagocytosis
A
CNS: astrocytes, ependymal, microglia
PNS: Schwann cells and microglial cells
25
How does the interstitial fluid composition resemble that of blood?
Similar due to the rapid passage of molecules from the blood through the endothelial wall into the interstitial fluid.
26
What two processes that normally occur in endothelial cells are missing from those in the brain?
transcapillary movement and transendothelial transport (fenestratrions and transpinocytosis)
27
What type of enzyme systems are present in endothelial cells of the brain?
drug metabolizing enzyme system for the metabolism of toxic chemicals and neurotransmitters
28
the drug metabolizing enzyme system of the brain is similar to that of which other organ?
liver
29
What do P-glycoproteins do? What do they need for this?
Pump hydrophobic molecules (or xenobiotics) out of the brain and into the blood. They are transmembranous, ATP-dependent efflux pumps.
30
Name four molecules or types that can passively diffuse across the BBB
water, oxygen, CO2, lipophilic substances
31
What is needed for choline to cross the BBB?
Phosphatidylcholine (from blood via a low-affinity transport system and from the synaptic cleft via high-affinity transport mechanism)
32
What type of fatty acids can and cannot cross the BBB?
Nonessential fatty acids cannot cross the BBB, essential fatty acids are transported across the BBB
33
Name the glucose transporters on the endothelial cells, neurons and glial cells.
Endothelial cells – both membranes via facilitated diffusion via GLUT1 transporter
Neurons – GLUT3 transporters
Glial cells – GLUT1 transporters
34
Which two cell types are referred to as "glial" cells?
oligodendrocytes and astrocytes
35
What can you infer is the approximate Km of GLUT1 (in mg/dL)?
60 mg/dL
36
In a person with normal blood [glucose] but 0.4X normal CSF [glucose] (hypoglycorrhachia), what transporter might be deficient?
GLUT1
37
Name 5 monocarboxylic acids that can be transported across the BBB into the brain.
L-lactate
Acetate
Pyruvate
Acetoacetate (ketone body)
Beta-hydroxybutyrate (ketone body)
38
What type of amino acids enter the brain through a single transporter. Which amino acid does it prefer? What do these AAs have in common?
Large neutral amino acids (LNAAs) F, L, Y, I, V, W, M, H enter via single amino acid transporter – L system amino acid transporter
It prefers Leucine, hence the “L” system name.
These are essential amino acids and must be imported for protein synthesis or as precursors for neutrotransmitters.
39
Can essential fatty acids cross the BBB?
yes
40
Why is entry of small neutral amino acids into the brain restricted?
The entry of small neutral amino acids is restricted because their influx could dramatically change the content of neurotransmitters.
Note: some examples of small neutral amino acids include A, G, P, and GABA
41
How do vitamins enter the brain?
Vitamins have specific transporters through the blood-brain barrier, just as they do in most tissues
42
List 3 proteins known to cross the BBB by receptor-mediated endocytosis.
1. insulin
2. transferrin
3. insulin-like growth factors
43
What are the two categories of neurotransmitters?
1. small nitrogen-containing molecules
| 2. neuropeptides
44
What does "adrenergic tract" mean?
Neuronal tract that synthesizes and releases the neurotransmitter epinephrine and norepinephrine.
45
What organ has opioid receptors?
Brain. Opioid receptors located within CNS
46
What type of neurotransmitter binds opioid receptors?
endorphins
47
what is the effect of endorphins?
block pain signals
48
What are two neuropeptide hormones that are synthesized in the brain but released into circulation?
GH and TSH
49
Where in the cell are neurotransmitters synthesized?
In the cytoplasm of the presynaptic terminal. Most of these neurotransmitters are synthesized from amino acids, intermediates of glycolysis and the TCA cycle and O2
50
How do the synthetic enzymes get to the site of neurotransmitter synthesis?
Transported by fast axonal transport from the cell body, where they are synthesized, to the presynaptic terminal
51
What is required to transport neurotransmitters into vesicles?
An ATP dependent pump linked to a proton gradient transports the NTs into the vesicles. So ATP is required.
52
What results from depolarization of the presynaptic membrane?
An influx of Ca2+ ions through voltage gated calcium channels
53
What is the signal that triggers vesicle fusion with the presynaptic membrane?
Influx of Ca2+
54
How is the neurotransmitter signal transmitted to the post-synaptic neuron?
Diffusion across synaptic cleft. Transmission of synapse is completed by binding of the neurotransmitter to a receptor on the postsynaptic membrane
55
List 4 ways that a neurotransmitter signal can be terminated.
1. Reuptake into the presynaptic terminal
2. Uptake into glial cells
3. Diffusion away from the synapse
4. Enzymatic inactivation
56
List 4 places that enzymatic inactivation of a neurotransmitter can occur.
Postsynaptic terminal
Presynaptic terminal
Adjacent astrocyte microglial cells
Endothelial cells in the brain capillaries
57
Name 2 reactions of catecholamine synthesis that require biopterin (BH4).
Phenylalanine → tyrosine → L-Dopa; steps 1 (phenylalanine hydroxylase) & 2 (tyrosine hydroxylase)
58
What is the rate-limiting step of catecholamine synthesis?
Hydroxylation of tyrosine via tyrosine hydroxylase, which requires BH4
59
Melanocytes produce a distinct tyrosine hydroxylase. What is it dependent on?
copper (Cu2+)
60
What condition results from a deficiency of melanocyte tyrosine hydroxylase?
albinism
61
What does DOPA stand for?
Dihydroxyphenylalanine
62
Dopa decarboxylase requires what co-factor and results in _____ of Dopa to _____.
Like many decarboxylation reactions, Dopa decarboxylase requires pyridoxal phosphate. Results in decarboxylation of Dopa to dopamine.
63
Some neurons produce an additional enzyme, ____ that converts Dopamine to ____.
Some neurons produce beta-hydroxylase found only within storage vesicles. They convert dopamine to norepinephrine.
64
Where is this enzyme located in the cell?
DBH is an enzyme found in storage vesicles of these cells
65
What 3 things does this enzyme require for its activity?
Cu2+ bound cofactor required for the electron transfer
Vitamin C – electron donor
O2
66
What is the electron donor in the dopamine beta-hydroxylase reaction ?
Vitamin C
67
What is the electron donor in the reaction above?
Transfer of methyl group converts NE to epinephrine. The cofactor required is SAM.
68
Epinephrine synthesis is dependent on which vitamins?
Vitamin B12 & folate (B9) in order to produce SAM
69
Why does transport of dopamine into vesicles require ATP?
Due to the high concentration of dopamine in storage vesicles, transporting more dopamine into vesicles would require ATP.
70
What is transported in opposition to dopamine? What is the name of this transporter?
A Proton is transported in opposition to dopamine via Vesicle Monoamine Transporter 2 (VMAT2)
Note: VMAT2 is homologous to p-glycoprotein. Also, H+ exchanged for positively charged catecholamines. p. 961
71
What does VMAT2 transporter have homology to?
Family of bacterial drug-resistance transporters, including P-glycoprotein
72
What is the ATP used for in the catecholamine storage transport system?
ATP is used for the proton pump, V-ATPase
73
What do call the type of transport used in the transport of catecholamines into storage vesicles?
secondary active transport
74
What are chromogranin? What are they complexed with?
Chromogranin are acidic proteins that are complexed with ATP and catecholamines in NT storage vesicles
75
How is catecholamine signaling terminated?
Catecholamine signaling is terminated through reuptake into the presynaptic terminal and diffusion away from the synapse. Degradative enzymes are present in the presynaptic terminal and in adjacent cells, including glial cells and endothelial cells.
76
What are the 2 major catecholamine degradative enzymes?
COMT and MAO
77
Which enzyme is located on the outer mitochondrial membrane? What does it remove from catecholamines?
MAO. It removes an ammonium ion by oxidizing the carbon (containing the amino group) to an aldehyde.
78
What additional compound (besides VMA) is produced when any catecholamine is oxidized?
NH4+, ammonium
79
Which isoform preferentially degrades serotonin and norepinephrine?
MOA-A
80
What enzyme uses SAM as a cofactor? What is the activity of this enzyme?
COMT; it transfers a methyl group from SAM to a catecholamine or its degradation product
81
Parkinson disease patients have _______________ in their CSF, indicating _______ degradation.
PD patients have decreased levels of cebrospinal homovanillymandelic acid (HVA) indicating dopamine degradation
82
What is a breakdown product of catecholamines that is excreted in the urine?
metanephrine
83
What supplies feedback inhibition of tyrosine hydroxylase?
Free cytosolic catecholamines compete at the binding site of the enzyme for cofactor, pterin.
84
How do free cytosolic decrease tyrosine hydroxylase activity?
These free cytosolic catecholamines decrease the activity of tyrosine hydroxylase by competing at the binding site of the enzyme for pterin cofactor (BH4)
85
What activates tyrosine hydroxylase?
The depolarization of the nerve terminal activates tyrosine hydroxylase
86
List 3 kinases that are activated by depolarization
PKC
PKA (cAMP dependent protein kinase)
CAM kinases (Ca2+-calmodulin dependent [CAM] kinases)
87
How do specific kinases activate tyrosine hydroxylase?
These phosphorylate tyrosine hydroxylase making it tighter to BH4 making it less sensitive to end-product inhibition
88
Longer term activation of catecholamines is accomplished by increased production of ____ &______.
Tyrosine hydroxylase and DBH
89
Increased transcription of specific genes is thought to result from increased _________ binding to ________.
This is due to phosphorylation of CREB by PKA which leads to CREB binding to CRE in the promoter region of the gene.
90
What is the first enzyme and cofactor in serotonin synthesis?
The first enzyme and cofactor in serotonin synthesis are tryptophan hydroxylase which requires BH4 to hydroxylate the ring structure of tryptophan
91
What happens in the second reaction of serotonin synthesis? What cofactor is involved?
The second reaction of serotonin synthesis is a decarboxylation. The cofactor involved is PLP. It involves the same enzyme in dopa decarboxylation (dopa decarboxylase)
92
The enzyme used in the second step of serotonin synthesis also uses __________ as a substrate
Dopa
93
Two reactions are required to convert serotonin into melatonin. What are they?
Serotonin -> N-acetyl serotonin (N-acetylation – Acetyl-CoA)
N-acetyl serotonin -> Melatonin (O Methylation – SAM)
94
Is melatonin production dependent on B12 and folate?
Yes, because it is dependent on SAM.
95
The first reaction in serotonin breakdown is catalyzed by ____ and also produces _____.
MAO-A, ammonia (NH3)
96
The second reaction in serotonin breakdown converts 5-hydroxyindole acetaldehyde to _______ and produces ______.
5-hydroxyindole acetic acid; NADH
97
What does heparin induced thrombocytopenia have to do with serotonin?
The heparin induces accumulation of anti-heparin antibodies which indirectly cause release of serotonin. Therefore, depending on the concentration of heparin, serotonin levels may indicate HIT. For instance, when using low concentration of heparin, HIT is present if >20% is released. Also, when using high concentrations of heparin, if <20% is released it would also indicate presence of HIT.
98
What happens when a person taking MAO inhibitor consumes red wine and cheese?
Those taking MAOI and consume red wine and cheese (which contain tyramine) would have increased levels of tyramine which induces the release of NE (from storage vesicles) and leads to life threatening hypertensive episodes.
Note: tyramine is a degradation product of tyrosine
99
What compound accumulates in the “cheese effect”?
tyramine
100
too much tyramine causes increased release of ___________
norepinephrine
101
which symptom(s) of the cheese effect is possibly life-threatening?
hypertension
102
What type of inhibitor is given for Parkinson disease but does not act as an antidepressant?
Deprenyl
Note: Clorygline is an antidepressant and suffers from the “cheese” effect.
103
Inhibiting which enzyme is effective for anxiety and depression?
MAO-A
104
An alternative to this enzyme inhibitor to treat anxiety & depression is a class of drugs called what?
SSRIs
105
The first of these SSRI drugs, _____brand, _______generic, can cause mild weight loss.
The first of these drugs, __Prozac__ brand, __Fluoxetine__ generic, can cause mild weight loss.
106
Two other SSRI drugs in this class are _____ and ______.
Two other drugs in this class are __Zoloft (Sertraline)__ and __Lexapro (Escitalopram).__
107
Combining therapeutic doses of _____drugs with _____ over the counter medication could cause mild symptoms of serotonin syndrome.
Combining therapeutic doses of __SSRI__ drugs with __Dextromethorphan__ over the counter medication could cause mild symptoms of serotonin syndrome?
108
What are the mild symptoms of serotonin syndrome?
Anxiety, agitation, restlessness, insomnia, tachycardia/tachypnea, hypotension/hypertension, dyspnea, flushing, diarrhea, incoordination, mydriasis, akathisia, ataxia
109
Combining ____ with a tricyclic antidepressant or an ____ could result in more severe forms of serotonin syndrome.
Combining __SSRI__ with a tricyclic antidepressant or an __MAOI__ could result in more severe forms of serotonin syndrome.
110
Histamine is produced from _____ in a _____ ______ reaction that requires ______ ______ cofactor.
Histamine is produced from __Histidine__ in a __single__ __enzymatic__ reaction that requires __pyridoxal__ __phosphate__ cofactor.
111
What is the enzyme that produces histamine? What cofactor is required?
Histidine decarboxylase
| PLP
112
What 2 cell types in the brain can produce histamine?
Mast cells and certain neuronal fibers
113
What is the first reaction for degradation of histamine in the brain? In what cells?
Methylation
| Astrocytes
114
The second reaction oxidizes methylhistamine & is catalyzed by _____, producing what by-product?
The second reaction oxidizes methylhistamine & is catalyzed by __MAO-B__, producing what by-product? NH4+
115
A second oxidation results in ______ ____ ___ and ____.
A second oxidation results in __methylimidazole__ __acetic__ __acid__ and __NADH__.
116
In peripheral tissues, histamine is oxidized by _____ ______.
In peripheral tissues, histamine is oxidized by __diamine__ __oxidase__.
117
A second oxidation in peripheral tissues results in ____ ____ ___ and ____.
A second oxidation in peripheral tissues results in __imidazole__ __acetic__ __acid__ and __NADH__.
118
Histamine in peripheral tissues is produced by ____ ______.
Histamine in peripheral tissues is produced by __histidine__ __decarboxylase__.
119
Is histamine excitatory or inhibitory in the brain?
Excitatory
120
What effect does histamine have in the lungs?
Airways constrict (in attempt to reduce intake of allergic material) so resulting bronchospasm, can lead to trouble breathing
121
What is the enzyme that synthesizes acetylcholine?
Choline acetyltransferase (ChAT)
122
What are the precursors of acetylcholine
Acetyl CoA and Choline
123
How does choline enter the brain?
Choline is taken up by the presynaptic terminal from the blood
124
Does the transporter from blood have a high or low Km?
Low affinity so high Km
125
What in the brain can serve as a storage site for choline?
Membrane lipids from hydrolysis of phosphatidylcholine and possibly sphingomyelin
126
Can humans synthesize choline? If yes, how?
Yes, as part of the pathway for the synthesis of phospholipids.
127
Can choline be synthesized in the brain?
Yes in the liver and brain phosphatidylcholine is hydrolyzed to release choline or phosphocholine. Conversion of phosphatidylethanolamine to phosphatidylcholine occurs there.
128
What vitamins are required for choline synthesis?
Folate and B-12 are required
129
What is the source of acetyl groups for acetylcholine synthesis?
Acetyl-CoA
130
Where in the cell is pyruvate converted to Acetyl CoA?
Pyruvate dehydrogenase is found only in mitochondria
131
Acetylcholine is synthesized in the cytoplasm. How does Acetyl CoA get there?
Acetyl group transported to cytoplasm where it is cleaved in cytosol to form acetyl-CoA and OAA
132
What enzyme inactivates acetylcholine? Where?
Acetylcholinesterase Neuromuscular junction
133
What symptoms result from inhibition of this enzyme?
Paralysis
134
What happens to the choline in the synapse?
Choline is taken up from the synaptic cleft via a high-affinity transport mechanism.
135
Does the synaptic transporter have a high or low Km?
Low Km (high affinity)
136
Does the placental choline transporter have a high or low Km?
Low Km (high affinity)
137
In neonates, does the blood brain barrier choline transporter have a high or low Km?
Low Km (high affinity)
138
What compound serves as the major dietary source of choline for neonates?
Phosphatidylcholine in Maternal milk
139
Is glutamate excitatory or inhibitory in the brain?
Excitatory
140
Is glutamate transported across the BBB?
No, not readily transported across the BBB.
| Glutamate is synthesized de novo within nerve terminals because it’s plasma concentration is low
141
What is the major source of glutamate precursors in the brain?
A-ketoglutarate
142
Where does the glutamate precursor, A-ketoglutarate, come from?
TCA cycle or transamination of AAs
143
Which 2 enzymes can convert this precursor to glutamate?
Glutamate dehydrogenase and PLP (transamination of AA to a-keto)
144
Which one requires pyridoxal phosphate?
Transamination
145
Another precursor for glutamate is _____, which comes from ____ cells.
Another precursor for glutamate is __glutamine__, which comes from __glial__ cells.
146
Is GABA excitatory or inhibitory?
Inhibitory
147
What is GABA synthesized from?
Glutamate
148
GABA synthesis is a _____ reaction that requires____ as a cofactor.
GABA synthesis is a __decarboxylation__ reaction that requires __PLP (needs B12)__ as a cofactor.
149
Most of GABA released at the synapse is taken up by ___ cells.
Most of GABA released at the synapse is taken up by __glial__ cells.
150
These glial cells convert GABA to ____ via the ____ ____.
These glial cells convert GABA to __glutamate__ via the __GABA shunt__.
151
Glutamate is converted to _____ in glial cells and released.
Glutamate is converted to __glutamine__ in glial cells and released.
152
What cells take up the glutamine and convert it to glutamate?
Neurons
153
Can glial cells synthesize GABA? Why or why not?
No, because they lack GAD.
154
Epilepsy and other convulsant disorders can be treated by drugs that inhibit _____ __ ____ ___ ___ _____.
Epilepsy and other convulsant disorders can be treated by drugs that inhibit __reuptake__ _of_ __GABA__ _from_ _the_ __synapse__.
155
Can Aspartate cross the BBB?
No
156
How is aspartate synthesized in the brain?
From the TCA cycle intermediate, OAA, via transamination reactions (which gets replaced via anaplerotic rxns)
157
Is Aspartate excitatory or inhibitory?
Excitatory
158
What is the major inhibitory neurotransmitter of the spinal cord?
Glycine
159
What is Glycine synthesized from?
De novo (within the nerve terminal) from serine by serine hydroxymethyltransferase enzyme, which requires folic acid
160
How is the signal produced by glycine probably terminated?
The uptake by a high-affinity transporter
161
NO is synthesized from ____by the enzyme____
| _____.
NO is synthesized from _arginine_______ by the enzyme___NO__ __synthase__.
162
What type of cells produce large amounts of NO to kill microbes and tumor cells?
Macrophages
163
What is the mechanism that NO uses to transduce a signal in endothelial cells?
NO readily crosses endothelial cell membranes —> activates guanylyl cyclase, which results in increased cGMP —> activation of protein kinases responsible for subsequent dilation of vessels
164
What is activated to cause smooth muscle relaxation in blood vessels?
NO activates soluble guanylate cyclase for cGMP→ Protein Kinase activation → Vasodilation
165
NO acts as a ________ to induce smooth muscle relaxation in the corpus _____.
NO acts as a __neurotransmitter__ to induce smooth muscle relaxation in the corpus __cavernosum to fill with blood (NO stimulates penile erection)__
166
Where is the NO synthesized: pre or post-synaptic neuron?
Post-synaptic Neuron
167
How is the NO signal terminated?
Phosphodiesterase breaks down cGMP
168
What unique properties does NO possess compared to other neurotransmitters?
NO can cross the cell membrane because it is a gas
169
Retrograde transmission involves release of neurotransmitters from the _____ _____ neuron.
Retrograde transmission involves release of neurotransmitters from the __presynaptic__ __terminal__ neuron.
170
What property of NO allows it to stimulate neighboring cells?
Gaseous Substance
171
How much of the body’s oxygen is used by the brain?
~20%
172
What organelle is important for this?
Mitochondria (glc converted to pyruvate in glycolysis and then pyruvate oxidized in TCA cycle cycle)
173
What is the major carbon source for the brain?
Glucose
174
In addition to producing more ATP, what is provided by aerobic metabolism?
CO2
175
What protective symptoms are initiated for protection against hypoglycemia?
Sweating, palpitations, anxiety, and hunger. Decreased Neurotransmitter synthesis
176
Hypoglycemia symptoms initiate in the sensory nuclei of the _______.
Hypoglycemia symptoms initiate in the sensory nuclei of the Hypothalamus.
177
How does the brain attempt to compensate for hypoglycemia?
The brain uses internal substrates such as glutamate and TCA cycle intermediates as fuel
178
When blood [glucose] of 2-2.5 mM, symptoms are thought to arise from decreased _____ __ ________.
When blood [glucose] of 2-2.5 mM, symptoms are thought to arise from decreased __synthesis__ _of_ __neurotransmitters __. (in particular regions of the brain rather than a global energy deficit)
179
Decreased glucose availability is like to affect 3 neurotransmitters in particular. What are they?
Glycine, glutamate, GABA, aspartate
180
Which pathways supply the precursors to the 3 neurotransmitters above?
Conversion of pyruvate to A-CoA in mito which generates a-ketoglutarate (for glutamate and GABA) and OAA (for aspartate), glycolysis - oxidation of glc to 3-PG (precursor for glycine)
181
Which cells are most susceptible to death in hypoglycemia below 1mM glucose?
Neurons
182
What neurotransmitter defect results from failure of energy-dependent reuptake pumps?
Glutamate excitotoxicity (build up of glutamate in cleft = overstim of postsynaptic glutamate receptors = prolonged activation = influx of lethal amounts of calcium ion = activation of cytotoxic intracellular pathways in postsyn neuron)
183
Overstimulation of the _____ receptor leads to prolonged opening of the ___ ___ channel, leading to intracellular pathways of cytotoxicity in the _____ neuron.
Overstimulation of the __glutamate__ receptor leads to prolonged opening of the __Ca__ __Ion__ channel, leading to intracellular pathways of cytotoxicity in the __postsynaptic__ neuron.
184
In mild hypoxia, what increases to maintain oxygen delivery to the brain?
Cerebral Blood Flow
185
Even “moderate” hypoxia of paO2 25 mm Hg, severe cognitive dysfunction occurs. Why?
Impaired neurotransmitter synthesis
186
In moderate hypoxia, what metabolic change occurs to maintain [ATP]?
Anaerobic glycolysis
187
What changes occur with the metabolic switch above?
Increased lactate production and decreased pH (usually leads to coma)
188
Why would pyruvate dehydrogenase activity be inhibited in the hypoxic brain?
Diminishes acetylcholine synthesis
189
What neurotransmitter is especially dependent on this enzyme?
ACh
190
When oxygen is unavailable to accept electrons, the concentration of ___increases.
When oxygen is unavailable to accept electrons, the concentration of __NADH__ increases.
191
When the compound above increases, what pathway is inhibited?
TCA
192
Name 2 major neurotransmitters that depend on TCA intermediates for their synthesis.
Glutamate and GABA
193
Name the 2 major anaplerotic reactions that supply the TCA cycle.
Pyruvate carboxylase reaction and the Degradative pathway of branched chain amino acids, valine and isoleucine, which contribute succinyl coA to the TCA cycle (methylmalonyl CoA mutase)
194
Which cells synthesize myelin in the CNS? PNS?
CNS - Oligodendrocytes.
| PNS - Schwann cells
195
What is the major type of component of myelin?
Lipids and proteins
196
What type of fatty acid is especially enriched in myelin?
Cerebroside
197
What are the 2 most prevalent proteins of myelin?
Proteolipid protein and myelin basic proteins (MBPs)
198
Which myelin protein is easily extracted from membrane?
Myelin Basic Proteins (MBPs)
199
Which protein is thought to stabilize the layered structure of myelin?
Proteolipid Protein
200
Phosphatidylinositol is at higher concentration in the membrane of _____ termini
Phosphatidylinositol is at higher concentration in the membrane of __Postsynaptic__ termini
201
List 4 membrane components that are constantly synthesized by the brain
Cholesterol, FA, glycosphingolipids, and phospholipids
202
Which cell type surrounds only 1 axon?
Schwann Cell
203
Which cell type surrounds multiple axons?
Oligodendrocytes
204
What type of lipid is most highly enriched in myelin compared to other cell membranes?
Cerebrosides
205
That choline is important for brain development is demonstrable by the high affinity transporters present in the placenta and at the neonatal BBB. Look at table 46.2 to determine why choline is so important.
More choline present in the gray matter so in the actual neurons, so choline deficiency inhibits development. In a developing brain even more choline is needed for the proper development of gray matter to occur.
206
There is more cerebroside than phosphatidylcholine in myelin? What advantage does this confer?
Yes, specifically galactosylcerebroside
| They pack more tightly together than phosphatidylcholine
207
Refsum disease is due to a defect in ______ _____.
Refsum disease is due to a defect in __peroxisome__ __biogenesis__.
208
Why would such a defect negatively affect the brain?
Severely affect brain cells because of the inability to metabolize both branched-chain and very-long-chain fatty acids.
209
Which of the 2 demyelinating diseases discussed is autoimmune?
Multiple sclerosis (MS) and Charcot-Marie- Tooth polyneuropathy syndrome
210
Which disease is a CNS defect?
Multiple sclerosis (MS)
211
Which disease is a PNS defect?
Charcot-Marie-Tooth polyneuropathy syndrome
212
What is the congenital defect in the PNS demyelinating disease?
Inherited mutations in P0 (major PNS myelin protein) - Autosomal dominant
