Metabolism of neurotransmitters
Vladimíra Kvasnicová
exam
questions:
4, 25-28,
31-33, 38
J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2nd edition, Thieme 2005
J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2nd edition, Thieme 2005
1-2)
voltage-gated
Na+_channels
depolariztion
3-4)
voltage-gated
K+_channels
hyperpolariztion
Na+/K+-ATPase
→ return to the
rest state
J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2nd edition, Thieme 2005
Overview of neurotransmitters
1. amino acids
excitatory: glutamate, aspartate
inhibitory: GABA (γ-aminobutyric acid), glycine
2. biogenic amines (monoamines)
catecholamines: dopamine and noradrenaline
serotonin, histamine
acetylcholine (quarternary ammonium cation)
3. peptides
endogenous opioids: endorphins, enkephalins, dynorphins
4. other
adenosine, anandamide, NO,...
Glutamate and GABA
synthesis (starts in astrocytes, Gln is then transported to neurons)
substrate: α-ketoglutarate (α-ketoGlt, Krebs cycle intermediate)
a) transamination to Glu (α-ketoGlt + any amino acid →
Glu + α-ketoacid; specific aminotransferase, PALP = pyridoxalphosphate) or
b) reductive amination to Glu (α-ketoGlt + NH3 + NADPH+H+ →
Glu + NADP+, glutamate dehydrogenase)
c) amidation of Glu (Glu + NH3 + ATP → Gln + ADP + Pi,
glutamine synthetase)
d) decarboxylation of Glu to GABA (Gln → Glu; glutaminase;
Glu → CO2 + GABA; PALP, glutamate decarboxylase)
degradation (Glu and GABA taken from synapses by astrocytes):
transamination: Glu → α-ketoGlt → Krebs cycle (KC)
GABA → succinate semialdehyde → succinate → KC
(transamination)
(dehydrogenation = oxidation)
Obrázek převzat z učebnice: J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2nd edition, Thieme 2005
GABA - shunt
Krebs cycle
succinate
oxidation
2-oxoglutarate
succinyl-CoA
succinate semialdehyde
decarboxylation
transamination
glutamate
Formation of Glu and Asp from Krebs cycle
intermediates: α-ketoglutarate and oxaloacetate
alanine
aminotransferase
(ALT = GPT)
aspartate
aminotransferase
(AST = GOT)
Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
Aspartate and Glycine
synthesis
Asp by transamination of oxaloacetate (Krebs cycle
intermediate): oxaloacetate + Glu → Asp + α-ketoGlt,
aspartate aminotransferase, enzyme: AST
Gly
from serine: Ser + THF → Gly + methylene-THF +
H2O (Ser can be synthesized from 3-phosphoglycerate =
intermediate of glycolysis)
degradation (reverse reactions of the synthesis)
Asp by transamination to oxaloacetate (enzyme: AST)
Gly
conversion to Ser, which can be degraded to pyruvate
glycolysis
Glycine synthesis
from http://www.biocarta.com/pathfiles/GlycinePathway.asp (Jan 2007)
Synthesis of
catecholamines
substrate: tyrosine
(= 4-hydroxyphenylalanine)
can be synthesized from
Phe (essential amino acid)
by hydroxylation
(phenylalanine hydroxylase,
tetrahydrobiopterin = THB);
DOPA
= 3,4-dihydroxyphenylalanine
Degradation of
catecholamines
enzymes: MAO and COMT
http://www.cvpharmacology.com/norepinephrine.htm
Degradation:
monoamine oxidase
CHO
catechol-O-methyl transferase
http://physrev.physiology.org/content/89/2/535
CHO
Synthesis of serotonin
THB
PALP
THB = tetrahydrobiopterin (cofactor of Trp-hydroxylase)
PALP = pyridoxalphosphate (cofactor of decarboxylase)
http://brainyinfo.com/neurotransmitters/neurotransmitter-serotonin/
Degradation of serotonin
5-hydroxyindole acetic acid
(5-HIAA)
http://www.pharmacorama.com/en/Sections/Serotonin_2_1.php
Histamine synthesis
degradation: histamine-N-methyl transferase
(N-methylation by S-adenosine methionine = SAM)
-CH3
adopted from http://www.sbuniv.edu/~ggray/CHE3364/b1c25out.html
Synthesis of
acetylcholine:
serine
ethanolamine
by acetylation of choline
(acetyl-CoA + choline)
choline can be
a) synthesized from
serine:
acetylcholine
choline
decarboxylation to
ethanolamine and methylation
by SAM to choline or
b) released from the phospholipid lecithine
(= phosphatidylcholine) by phospholipase
Degradation: by acetylcholine esterase (in synaptic cleft)
to choline and acetate, choline then undergoes re-uptake
http://quizlet.com/5858500/module-1-cholinergics-and-anticholinergics-flash-cards/
http://web.campbell.edu/faculty/nemecz/323_lect/Nitrogen_metabolism/images/choline.jpg
Obrázek převzat z učebnice: J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2nd edition, Thieme 2005
Endogenous opioids
are neuropeptides synthesized from larger precursor
polypeptides by alternative hydrolysis
endorphins: from proopiomelanocortin (POMC)
→ β-endorphin (31 amino acids)
enkephalins: from proopiomelanocortin or proenkephalin or *
→ met-enkephalin, leu-enkephalin (pentapeptides)
dynorphins: from prodynorphin *
→ dynorphin A, dynorphin B, neoendorphin
nociceptin (= orphanin FQ; 17 amino acids): from pronociceptin
https://www.glowm.com/resources/glowm/cd/pages/v5/v5c010.html