Biochem-Ch. 48 Flashcards
1
Q
What are the important peptide neurotransmitters?
A
Beta-endorphin
Met-enkaphalin
Leu-enkaphalin
Somatostatin
Substance P
Neurotensin
Vasoactive intestinal peptide
2
Q
What is the important difference between the peptide NT and the small molecule NT?
A
-The peptide NT are heteropolymers of amino acids (peptides)
3
Q
What are the small molecule NT of importance?
A
Acetylcholine
Dopamine
Norepinepherine
Epinepherine
Serotonin
Melatonin
Histamine
4
Q
Which of the NT are derived from tyrosine?
A
DA, Epi, and NE
5
Q
Which of the small molecule NT are derived from Tryptophan?
A
- 5-HT (serotonin) and Melatonin
- remember these are bicyclic compounds
6
Q
Which of the small molecule NT is derived from Histadine?
A
-Histamine…DUR
7
Q
What are the impiortant amino acid NT?
A
Glutamate (Glu)
Aspartate (Asp)
Glycine (Gly)
GABA (gamma-aminobutyric acid)
Serine (Ser)
Cysteine (Cys)
8
Q
What are the important purigenic or nucleic acid NT?
A
Adenosine
ATP
9
Q
What are the three catcholamines? What are they derived from?
A
- Dopamine, NE and Epi
- Tyrosine–> which can be made from phenylalanine, therefore the catecholamines can be derived from either
10
Q
What enzyme is responsible for the conversion of phenylalanine to tyrosine in the liver?
A
-Phenalanine hydroxylase
11
Q
What is the rate limiting enzyme in the sythesis of catacholamines? What does it catalyze?
A
- Tyrosine hydroxylase
- catalyzes the conversion of tyrosine to Dopa (L-DOPA)
12
Q
What coenzyme is required for the conversion of L-Tyrosin to L-Dopa by tyrosine hydroxylase?
A
Tetrahydrobiopterin (BH4)
13
Q
Where is tyrosine hydroxylase found?
A
-only in catecholamine cells
14
Q
What enzyme and therefore pigment is lacking or defective in individuals with albinsism?
A
- A defect in the copper dependant tyrosine hydroxylase of melanocytes (different than TH in the adrenal medulla)
- no conversion of DOPA to melanin
15
Q
What enxyme is responsible for the conversion of L-DOPA to Dopamine?
A
DOPA decarboxylase
16
Q
Where does the DOPA decarboxylase reaction take place?
A
In the cytoplasm
17
Q
What is the immediate precursor to NE?
A
Dopamine (DA)
18
Q
What enzyme is responsible for the conversion of DA to NE?
A
Dopamine-ß-hydroxylase or DbH
19
Q
What cofactors are essential for the conversion of DA to NE by dßh?
A
- Vitamin C
- O2
- Cu
20
Q
What enzyme is responsible for the conversion of NE to Epi?
A
phenylethanolamine N-methyl-transferase
(PMNT)
21
Q
What coenzyme is required by PMNT for the conversion of NE to Epi?
A
SAM
22
Q
What is required for the synthesis of SAM?
A
Folic Acid and vitamin B12
23
Q
What is the general pathway requiring the use of B12 and Folic acid?
A
- Folic Acid donates a methyl group to B12
- B12 then donates that methyl group to homocysteine–>methionine which eventually forms SAM.
- That methyl group is then donated to the substrate and SAM is recycled.
**note the difference in NE and Epi is the addition of a methyl group! Neat-o
24
Q
What would the result of a deficiency vitamin C?
A
Lack of dßh function
–> leading to a lack of conversion of DA to NE
25
A defect in the SAM pathway (folic acid or B12 deficiency) would lead to a build up of what small molecule NT?
NE
-SAM converts NE--\>Epi
26
After conversion from L-DOPA to DA in the cytosol, where are the NT moved?
-Into starage vesicles where the conversion from DA to NE will take place in NE containine neurons
27
What is the enzyme responsible for the transport of catcholamines into vesicles?
Vessicle monoamine transporter 2
| (VMAT2)
28
What small NT conversions take place in the cytosol?
L-tyrosine--\> L-DOPA --\> Dopamine
29
What transformations, if needed, take place in storage visicles?
DA--\> NE
and
NE--\> Epi
30
How does proton pumping play into the transport of catecholamines into storage vesicles?
-A high proton concentraction (acidic) is establised inside of the vesicle by and H+/ATP pump
The efflux of H+ is then linked to the influx of catecholamines through this **secondary active transport**
31
How many transmembrane domains does VMAT2 have?
12
32
What is a chromogranin?
the soluble content of a storage vesicle
-includes NT and d
33
How is reuptake of NT after release mediated?
-Through Na dependant reuptake
34
What is the role of monoamine oxidase (MAO) in catecholamine degredation?
-oxidizes the carbon containing amino group to an aldehyde
35
How does Catechol-O-methyltransferase (COMT) help to inactivate catecholamines?
-transfers a methyl group from SAM to the extracellular catcholamine.
36
Since COMT employs the use of SAM, what coenzymes are indirectly required for its proper operation?
-vitamin B12 and Folate
37
What is tyramine? What does it have to do with MAO?
-Tyramine is the degradation product of Tyrosine
Tyramine is usually inactivated by MAO-A
38
Are the metabolisms of NE and Epi similar?
Yes, almost identical
39
What is homovanillylmandelic acid (HVA) a marker of?
- Dopamine turnover
- typically found in the CSF, Blood and urine
40
What is VMA an indicator of?
NE and Epi turnover
41
How is tyrosine hydroxylase inhibited?
-by free cytosolic catecholamines
(if catecholamines are high, TH does not want to make more)
42
What factors contribute to the activation of TH during neuronal stimulation?
-Depolarization of the neuron activates PkA and PkC which phosphorylate TH and result in tight binding of it to BH4
43
What is the long term effect of excess stimulation of TH and dopamine levels?
Prolonged stimulation results in the increase of TH and Dopamine in the nerve terminals.
44
How is the synthesis of 5-HT similar to dopamine synthesis?
- a similar enzyme (tryptophan hydrogenase) is used in the conversion of tryptophan to 5-HT
- then the exact same enzyme DOPA decarboxylase is used in the decarboxylation of 5-HT to serotonin
45
Is the coenzyme used by tryptophan hydroxylase similar to the one used by TH?
-Yep. Exactly the same one--\> BH4
46
In the conversion of Serotonin to melatonin, what enzyme is common?
-conversion of SAM to SAH in the methyl transfer of N-acrtylserotonin--\> melatonin
47
What enzymes assists in the breakdown and inhibtion of DA and serotonin?
-MAO
48
Is visicle uptake and storage of 5-HT similar to that of DA? How does it differ?
- Yes (secondary active Via H+ gradient)
- Transport by both VMAT1 and VMAT2
- binds to 5-HT binding protein (Iron heme) once in the vesicle
49
How do MAO-Is treat depression?
-They block the breakdown of 5-HT, NE and DA in the wall of the mitochondria and increase their concentration
50
What is an SSRI? What is it used to treat?
- Selective serotonin reuptake inhibitor
- Blocks the reuptake of 5-HT and used to treat depression
51
What kind of drugs are 5-HT1 agonists?
Anti-anxiety drugs
52
What drug is a 5-HT2 agonist? So then
-LSD
53
What receptors do antipsychotics act on?
5-HT2 antagonists
54
What are 5-HT3 antagonists used for?
The treatment of chemotheraphy nausea
55
How is the degrdation of histamine different from most other NT?
Histamine is not recycled into the presynaptic terminal
56
Where is histamine inactivated and degraded?
Astorcytes
57
What cells use histamine in thebrain?
Mast cells
58
What enzyme is resposible for the synthesis of Acetylcholine?
Choline Acetyltransferase
| (ChAT)
59
What is the location of ACh synthesis?
-Presynaptic terminal
(then it is transferred into vesicles)
60
Where does the choline for acetylcholine norammyl come from?
- Common part of the diet
- Can also be synthesized as part of the synthesis of phospholipids
61
How is vitamin B12 indirectly involved in the synthesis of choline?
-In the endogenous synthsis of choline, methyl groups are sequentially added by SAM.
--\> SAM needs vitamin B12 to reconstitute its methyl group
62
Is the mechansim for transport of ACh similar to other NT?
Yes.
- 12 membrane H+ countertransporter
- H+/ATP pump
63
What enzyme is resposible for the inactivation of acetylcholine?
-Acetylcholinesterase
64
How can glutamate be synthesized from glutamine?
With the use of glutaminase
65
Where does the glutamine used to sythesize glutamate come from?
Glial cells
66
What TCA cycle intermediate can be converted into glutamate? What are the two ways in which this can take place?
- Alpha-ketogluterate
- this can be accomplised by either **adding free ammonia** to glutamate **or by transamination** from other amino acids.
67
How is GABA synthesized?
-by decarboxylation of glutamate
68
What enzyme is responsible for the decarboxylation of glutamate to GABA?
Glutamic acid decarboxylase
69
How are GABA and glutamate deactivated and transported?
- Glial cells **uptake GABA which is converted to glutamate**
- this and the rest of the glutamate is **then converted to glutamine** and transported to neurons where it is **converted back to glutamate**
70
What is the main function of aspartate?
-Excitatory NT, cannot pass through the BBB
71
What is the main function of glycine?
-Major inhibitory NT of the spinal cord
72
What is the only **Metabotropic triggered outward potassium channel**? Is it inhibitory or excitory?
GABAB
-inhibitory
73
From what AA is NO synthesized from?
Arginine
74
What are the functions of NO?
75
How much of the oxygen supply of the body does the brain use?
20%
76
What is the brain's main supply of energy? What can it use during persiods of fasting or development?
- Glucose is the main fuel
- Ketone bodies can be used if absolutely needed
77
When the blood glucose falls below 45mg/dL what does the brain first try to use as fuel?
-internal substrates like **glutamate** and **TCA cycle intermediates**
78
Why does neural activity begin to fall as teh blood glcose level drops below 45mg/dL?
The brain reduces sythesis of certain NT.
79
What happens if blood glucose falls below 1mM or 18mg/dL?
- ATP supplies are depleated
- neruonal death insues as the EEG becomes isoelectric
80
What NT are most dependant on glucose levels?
Glycine
Aspartate
Glutamate
81
What is the cause of cognitive dysfunction in hypoxic patients?
Impaired neurotransmitter synthesis
82
Does mild hypoxia cause an increase or a decrease in the blood supply to the brain?
Increase to maintain O2 delivery
83
What is the effect of glutamate synthesis on the energy system of the brain?
Glutamate synthesis removes Alpha-ketogluterate from the TCA cycle causing a reduction in oxaloacetate.
-Slows down the TCA cycle
84
How does the BBB impact lipid transfer into the brain?
BBB restricts the movement of non-essential fatty acids across the barrier. (Palmitate)
85
Which lipds can enter the brain?
-Essential fatty acids like:
--lioleic acid
--linolenic
86
Which lipids are synthesized within the brain?
Cholesterol
Glycerol
Sphingolipids
glycophingolipids
Cerebrosides
-**Very long chain fatty acids** used in myelin formation
87
How and where are the brains very long chain fatty acids catabolized?
-Within peroxisomes by alpha-oxidation
88
What is myelin?
A multilayered lipid and protein structure that is formed from the plasma membrane of glial cells
PNS: Schwann cell--\> sinlge axon
CNS: oligodendrocyte--\> multiple axons
89
What are the two most important structural myelin proteins?
- Myelin basic protein (MBP)
- proteolipid protein
90
What is important about antibodies directed against MBP?
-Helps in the understanding of MS
91
Is MBP positively charged or negatively charged? What face of the myelin membrane does it lie upon?
- Positively charged
- cytoplasmic face
