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Biochemistry - Sarah > Neurotransmitters > Flashcards

Neurotransmitters Flashcards

1
Q

Overview of neurotransmitters

A

many are biogenic amines, derived from amino acids by a few simple steps

tyrosine to catacholamines and thyroid hormones
tryptophan to serotonin and melatonin
histidine to histamine
glutamate to gamma-aminobutyric acid (GABA)
Endorphins and enkephlins (opioid activity) are peptide hormones cleaved from proteins

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2
Q

Tyrosine creates ___.

A

Catacholamines (dopamine, norepinephrine, epinephrine, serotonin) and thyroid hormones

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3
Q

Histidine creates ___.

A

Histamine (requires pyridoxal phosphate)

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4
Q

Tryptophan creates ___.

A

Serotonin and melatonin

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5
Q

Glutamate creates ___.

A

GABA (Gamma-aminobutyric acid)

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6
Q

Reaction types that convert amino acids to neurotransmitters

A

decarboxylation, hydroxylation, and SAM (methylations)

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7
Q

What maintains the blood-brain barrier?

A

Astrocytes and microglia

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8
Q

Function of astrocytes

A

Phagocytosis of debris, nutritional support for neurons (lactate)

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9
Q

Astrocytomas

A

most common supratentorial intra-axial tumor in all age groups and the most common brain tumor in children

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10
Q

microglia function

A

“macrophages of brain”, immunologically responsive

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11
Q

Xenobiotics are pumped out by ____. (blood-brain barrier question)

A

ABC transporters

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12
Q

What are some things that can cross the blood-brain barrier?

A

essential fatty acids, glucose, (xenobiotics pumped out by ABC transporters)

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13
Q

What are some things that cannot cross the blood-brain barrier?

A

Non-drowsy antihistamines, non-essential fatty acids

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14
Q

What are the glucose receptors related to the blood-brain barrier?

A

GLUT1 is used by endothelial cells. GLUT3 is used by neurons

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15
Q

Examples of neurotransmitters

A

Glutamate and aspartate: major excitory neurotransmitters (cortex, cerebellum, spinal cord)

GABA: major inhibitory neurotransmitter in the brain

Serotonin: affects mood, sleep, apetite (regulated by tryptophan uptake and monoamine oxidase degradation)

Acetylcholine: neurotransmitter primarily for motor neurons

Norepinephrine: stress hormone (released by tyrosine hydroxylase and monoamine oxidase)

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16
Q

Glutamate and aspartate

A

major excitory neurotransmitters (cortex, cerebellum, spinal cord)

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17
Q

GABA

A

major inhibitory neurotransmitter in the brain, from glutamate

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18
Q

Serotonin

A

affects mood, sleep, apetite (regulated by tryptophan uptake and monoamine oxidase degradation)

Regulates sleep, temperature, and blood pressure
Powerful vasoconstrictor and stimulator of smooth muscle

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19
Q

Acetylcholine

A

neurotransmitter primarily for motor neurons

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20
Q

Norepinephrine

A

stress hormone (released by tyrosine hydroxylase and monoamine oxidase)

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21
Q

Catecholamine examples

A

dopamine, norepinephrine, epinephrine

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22
Q

Functions of catecholamines

A

fight or flight response
bind alpha and beta adrenergic receptors
alter intracellular concentrations of calcium and cAMP

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23
Q

General affects of catecholamines

A

increase glycogen degradation and release of glucose into the blood
increase triglyceride hydrolysis and release of fatty acids from adipose tissue
increase release of glucagon from pancreatic alpha cells
increase glycogen degradation in muscle

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24
Q

Rate-limiting step of formation of catecholamines

A

tyrosine hydroxylase

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25
Regulation of catecholamines
rate limiting step is tyrosine hydroxylase feedback inhibition by dopamine and norepinephrine activated by cAMP-dependent phosphorylation Metabolized rapidly. Short half lives (15-30 seconds). Inactivated by 2 enzymes (Catecholamine-O-methyltransferase or COMT and Monoamine oxidase or MAO) to form vanillylmandelic acid (VMA)
26
Epinephrine
Tyrosine derivative hormone (catecholamine) made in adrenal medulla and sympathetic nerve endings binds beta2-adrenergic receptors --> G proteins --> cAMP increase --> phosphorylation (PKC + Calcium) Responsible for rapid mobilization of energy and glucose Fight or Flight: immediate increase in blood glucose through liver and muscle glycogenolysis
27
Difference between epinephrine and norepinephrine
Norepinephrine has amine group on end, epinephrine has methyl group on end
28
Where is epinephrine made?
in the adrenal medulla and sympathetic nerve endings
29
Defective tyrosine hydroxylase in melanocytes leads to ____.
Albinism
30
dopa decarboxylase requires ___ as a cofactor.
PLP (vitamin B6, pyridoxine)
31
Dopamine beta-hydroxylase requires ___ as a cofactor.
Vitamin C
32
Phenyl-ethanolamine N-methyl transferase requires ___ as a cofactor.
SAM (S-adenosyl methionine)
33
Dopa decarboxylase makes ___ from ___.
dopamine from dopa
34
Dopamine beta-hydroxylase makes ___ from ___.
norepinephrine from dopamine
35
Phenyl-ethanolamine N-methyl transferase makes ___ from ___.
epinephrine from norepinephrine
36
Pheochromocytoma
Catecholamine-secreting tumor Adrenal gland tumor Excessive secretion of norepinephrine or epinephrine May precipitate life-threatening hypertension or cardiac arrythmias Symptoms include headache, palpitations with severe hypertension (worsen with time) Rare diagnostic test: elevated metanephrine in urine
37
How do you test for pheochromocytoma?
elevated metanephrine in urine
38
Catecholamine inactivation
monoamine oxidase converts norepinephrine or epinephrine to 3-methoxy-4-hydroxymandelic acid (or VMA, vanillylmandelic acid) They also have an oxidation step. Norepinephrine has a step that uses SAM/COMT.
39
Parkinson's disease
caused by a degeneration of dopamine producing neurons in the substantia nigra Lewy bodies also present Decreased motor cortex stimulation by basal ganglia Levodopa can treat it Carbidopa used in conjunction to inhibit L-amino acid decarboxylase in peripheral tissues (it cannot cross the blood-brain barrier)
40
Melatonin is a product of __.
Serotonin
41
Serotonin synthesis requires ___.
BH4 (and tryptophan and oxygen) | tyrosine hydroxylase also requires BH4
42
Melatonin is produced by the ___.
pineal gland
43
Melatonin synthesis requires __.
SAM and Acetyl CoA
44
Examples of selective serotonin reuptake inhibitors
prozac, fluoxetine, zoloft, and celexa
45
Serotonin syndrome
Use of serotonin reuptake inhibitors and monoamine oxidase inhibitors together causes this Symptoms: cognitive behavior such as confusion, disorientation, neuromuscular such as muscle spasms, and autonomic nervous system including fever, sweating, and high blood pressure 93 deaths estimated in 2002
46
Histamine
Chemical messenger formed from histidine (requires pyridoxal phosphate) Causes allergic and inflammatory reactions Released from mast cell present in thalamus, dura mater leptomeninges and choroid plexus Powerful vasodilator of blood vessels, expand capillaries,, localized edema, drop in blood pressure Lungs: constricts bronchioles Stomach: stimulates HCl secretion in the Brain: Neurotransmitter Activates postynaptic and presynaptic receptors removed by astrocytes believed to have role in sleep regulation
47
What is the end product of histamine inactivation?
In peripheral tissues, it is imidazole acetic acid. In the brain, it is methylimidazole acetic acid. The brain converts histamine to methylhistamine
48
Acetylcholine is broken down into ___ by ___.
acetic acid and choline, by acetylcholinesterase
49
Choline synthesis requires ___ (donated by SAM) to phosphatidylethanolamine.
3 methyl transfers
50
Acetylcholine activates ____.
muscarinic receptors
51
Acetylcholinesterase inhibitors
Sarin and parathion
52
Antidote to acetylcholinesterase inhibitors
Atropine (blocks access to the muscarinic receptors)
53
How are some patients with myasthenia gravis treated?
They are given pyridostigmine to inhibit acetylcholinesterase, which helps make up for the lack of acetylcholine receptors
54
Nitric oxide
Free radical diatomic gas that can diffuse through membranes half life is seconds Arginine + NADPH ---> citrulline + nitric oxide + NADP+
55
Cofactors of nitric oxide synthase
Contain FAD, FMN, and cytochrome-like heme prosthetic groups in a single polypeptide chain
56
Three genes identified for NOS isoforms
Neuronal NOS-I: activated by NMDA receptor stimulation (Glu) Cerebral blood flow, smooth muscle relaxation (Viagra inhibits cGMP phosphodiesterase 5, enhancing smooth muscle relaxation, blood flow, male erection) Macrophage or induced (NOS-II) Endothelial (NOS-III), constitutive
57
Mechanism of nitric oxide
enters the smooth muscle, stimulates guanylate cyclase to produce cGMP which results in smooth muscle relaxation (blood vessel dilation)
58
What does Viagara do?
Viagra inhibits cGMP phosphodiesterase 5, enhancing smooth muscle relaxation, blood flow, male erection
59
Refsum's disease
build up of phytanic acid (chlorophyll) in peroxisomes. Lack hydroxylation enzyme for degredation
60
Mucopolysaccharidoses
Group of inherited metabolic disorders caused by a deficiency in one of the specific lysosomal enzymes needed to break down mucopolysaccharides Period of normal development followed by a decline in physical and/or mental function
61
Hurler syndrome
mucopolysaccharidoses in which alpha-iduronidase is deficient. Results in accumulation of glycosaminoglycan, heparan, and dermatan sulfate. Has corneal clouding.
62
Hunter syndrome
mucopolysaccharidoses in which Iduronate sulfatase (required for degredation of sugar linkages) is deficient. Glycosaminoglycan, heparan, and dermatan sulfate accumulate. Does not have corneal clouding.
63
Glycoprotein synthesis
N-glycosylation of proteins is more complex than o-glycosylation. Oligosaccharides are assembled on membrane bound dolichol phosphate. Dolichols consist of long poly-isoprene units
64
Glycoproteins
Sugar chains, often branched, do not have repeating disaccharides Excludes proteoglycans Found in most blood proteins, ECM proteins: collagen. Secretions of mucus-producing cells, cell surface proteins (blood groups), lysosomal and ER membrane associated proteins
65
Glycolipids
lipid sphingosine + sugars cerebrosides, sulfatides, globosides, gangliosides (have at least one sialic acid (NANA) residue) Polar head group (sugars) is attached to ceramide by a glycosidic bond at the terminal hydroxyl of sphingosine
66
Ganglioside have at least one ____ residue.
sialic acid (NANA)
67
Defective protein in Farber's diease
ceramidase
68
Defective protein in Gaucher's disease
glucocerebroside
69
Defective protein in Krabbe's disease
galactocerebroside
70
Defective protein in Tay-Sach's disease
hexosaminidase A
71
Defective protein in Neimann-Pick disease
Sphingomyelinase
72
Defective protein in Gm1 gangliosidosis
GM1-beta-galactosiase
73
Product accumulated in Gaucher's disease
glucosylceramide
74
Accumulation of glycosphingolipids indicates ___.
Fabry disease
75
Accumulation of GM2 ganglioside indicates ____.
Tay-Sach's disease
76
Product accumulated in Farber's disease
Sphingosine ceramide
77
Gaucher's disease
Cause by buildup of glucosylceramide and defective glucocerebroside. Hepatosplenomegaly occurs. Diagnostic lipid-laden macrophages ("crinkled paper appearance") termed Gaucher cells are present

Biochemistry - Sarah (12 decks)

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