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Flashcards in Neurotransmitters Deck (77):
1

Overview of neurotransmitters

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

2

Tyrosine creates ___.

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

3

Histidine creates ___.

Histamine (requires pyridoxal phosphate)

4

Tryptophan creates ___.

Serotonin and melatonin

5

Glutamate creates ___.

GABA (Gamma-aminobutyric acid)

6

Reaction types that convert amino acids to neurotransmitters

decarboxylation, hydroxylation, and SAM (methylations)

7

What maintains the blood-brain barrier?

Astrocytes and microglia

8

Function of astrocytes

Phagocytosis of debris, nutritional support for neurons (lactate)

9

Astrocytomas

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

10

microglia function

"macrophages of brain", immunologically responsive

11

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

ABC transporters

12

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

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

13

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

Non-drowsy antihistamines, non-essential fatty acids

14

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

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

15

Examples of neurotransmitters

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)

16

Glutamate and aspartate

major excitory neurotransmitters (cortex, cerebellum, spinal cord)

17

GABA

major inhibitory neurotransmitter in the brain, from glutamate

18

Serotonin

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

19

Acetylcholine

neurotransmitter primarily for motor neurons

20

Norepinephrine

stress hormone (released by tyrosine hydroxylase and monoamine oxidase)

21

Catecholamine examples

dopamine, norepinephrine, epinephrine

22

Functions of catecholamines

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

23

General affects of catecholamines

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

24

Rate-limiting step of formation of catecholamines

tyrosine hydroxylase

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