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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
Q

Regulation of catecholamines

A

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)

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26
Q

Epinephrine

A

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

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27
Q

Difference between epinephrine and norepinephrine

A

Norepinephrine has amine group on end, epinephrine has methyl group on end

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28
Q

Where is epinephrine made?

A

in the adrenal medulla and sympathetic nerve endings

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29
Q

Defective tyrosine hydroxylase in melanocytes leads to ____.

A

Albinism

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30
Q

dopa decarboxylase requires ___ as a cofactor.

A

PLP (vitamin B6, pyridoxine)

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31
Q

Dopamine beta-hydroxylase requires ___ as a cofactor.

A

Vitamin C

32
Q

Phenyl-ethanolamine N-methyl transferase requires ___ as a cofactor.

A

SAM (S-adenosyl methionine)

33
Q

Dopa decarboxylase makes ___ from ___.

A

dopamine from dopa

34
Q

Dopamine beta-hydroxylase makes ___ from ___.

A

norepinephrine from dopamine

35
Q

Phenyl-ethanolamine N-methyl transferase makes ___ from ___.

A

epinephrine from norepinephrine

36
Q

Pheochromocytoma

A

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
Q

How do you test for pheochromocytoma?

A

elevated metanephrine in urine

38
Q

Catecholamine inactivation

A

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
Q

Parkinson’s disease

A

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
Q

Melatonin is a product of __.

A

Serotonin

41
Q

Serotonin synthesis requires ___.

A

BH4 (and tryptophan and oxygen)

tyrosine hydroxylase also requires BH4

42
Q

Melatonin is produced by the ___.

A

pineal gland

43
Q

Melatonin synthesis requires __.

A

SAM and Acetyl CoA

44
Q

Examples of selective serotonin reuptake inhibitors

A

prozac, fluoxetine, zoloft, and celexa

45
Q

Serotonin syndrome

A

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
Q

Histamine

A

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
Q

What is the end product of histamine inactivation?

A

In peripheral tissues, it is imidazole acetic acid. In the brain, it is methylimidazole acetic acid. The brain converts histamine to methylhistamine

48
Q

Acetylcholine is broken down into ___ by ___.

A

acetic acid and choline, by acetylcholinesterase

49
Q

Choline synthesis requires ___ (donated by SAM) to phosphatidylethanolamine.

A

3 methyl transfers

50
Q

Acetylcholine activates ____.

A

muscarinic receptors

51
Q

Acetylcholinesterase inhibitors

A

Sarin and parathion

52
Q

Antidote to acetylcholinesterase inhibitors

A

Atropine (blocks access to the muscarinic receptors)

53
Q

How are some patients with myasthenia gravis treated?

A

They are given pyridostigmine to inhibit acetylcholinesterase, which helps make up for the lack of acetylcholine receptors

54
Q

Nitric oxide

A

Free radical diatomic gas that can diffuse through membranes
half life is seconds
Arginine + NADPH —> citrulline + nitric oxide + NADP+

55
Q

Cofactors of nitric oxide synthase

A

Contain FAD, FMN, and cytochrome-like heme prosthetic groups in a single polypeptide chain

56
Q

Three genes identified for NOS isoforms

A

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
Q

Mechanism of nitric oxide

A

enters the smooth muscle, stimulates guanylate cyclase to produce cGMP which results in smooth muscle relaxation (blood vessel dilation)

58
Q

What does Viagara do?

A

Viagra inhibits cGMP phosphodiesterase 5, enhancing smooth muscle relaxation, blood flow, male erection

59
Q

Refsum’s disease

A

build up of phytanic acid (chlorophyll) in peroxisomes. Lack hydroxylation enzyme for degredation

60
Q

Mucopolysaccharidoses

A

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
Q

Hurler syndrome

A

mucopolysaccharidoses in which alpha-iduronidase is deficient. Results in accumulation of glycosaminoglycan, heparan, and dermatan sulfate. Has corneal clouding.

62
Q

Hunter syndrome

A

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
Q

Glycoprotein synthesis

A

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
Q

Glycoproteins

A

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
Q

Glycolipids

A

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
Q

Ganglioside have at least one ____ residue.

A

sialic acid (NANA)

67
Q

Defective protein in Farber’s diease

A

ceramidase

68
Q

Defective protein in Gaucher’s disease

A

glucocerebroside

69
Q

Defective protein in Krabbe’s disease

A

galactocerebroside

70
Q

Defective protein in Tay-Sach’s disease

A

hexosaminidase A

71
Q

Defective protein in Neimann-Pick disease

A

Sphingomyelinase

72
Q

Defective protein in Gm1 gangliosidosis

A

GM1-beta-galactosiase

73
Q

Product accumulated in Gaucher’s disease

A

glucosylceramide

74
Q

Accumulation of glycosphingolipids indicates ___.

A

Fabry disease

75
Q

Accumulation of GM2 ganglioside indicates ____.

A

Tay-Sach’s disease

76
Q

Product accumulated in Farber’s disease

A

Sphingosine ceramide

77
Q

Gaucher’s disease

A

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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