Pheripheral Nervous system

(Neurotransmitter)

Santoso
Dept of Biochemistry
Diponegoro University
Semarang
Purposes :
 Neurotransmitter definition
 Neurotransmitter of autonomic nerve system
 Neurotransmitter of somatic nerve system
 Mechanisms of biosynthesis of acethylcholine,
ephinephrine, and norephinephrine.
 Mechanisms of of acethylcholine, ephinephrine, and
norephinephrine release
 Interaction of of acethylcholine, ephinephrine, and
norephinephrine on their receptors
 Degradation of of acethylcholine, ephinephrine, and
norephinephrine
Why we can walk or run?
Component of Neuromuscular system

 Central nervous system

 Pheripheral nervous system
 Neuromuscular junction
 Muscle
 Bone and joints
 Nervous System
 Consist of :
 Two neurons which is connected 
synapse
 Neuron is the longest cell in our body
Stage of Muscle Contraction

 Nerve  Neuromuscular junctionMuscle

 Processes involving :
 Action potential
 Transmission of impulses
 Release Neurotransmitter
 Contraction
 Relaxation
 Neurotransmiter
• Senyawa kimia pembawa pesan yang
meneruskan impuls dari satu neuron ke neuron
lain atau sel efektor.
• Sifatnya :
• Disintesis di neuron presinaps
• Disimpan di vesikel dalam neuron presinaps
• Dilepaskan dari neuron di bawah kondisi
fisiologik
• Segera dipindahkan dari sinaps melalui uptake
atau degradasi
• Berikatan dengan reseptor menghasilkan
respon biologik
 Klasifikasi (1)
 Berdasarkan efek yang muncul :
• Eksitatorik
 Asetilkolin
 Aspartat
 Dopamin
 histami
• Inhibitorik
 Klasifikasi (2)
• Bentuk molekul :
• Small-molecule transmitters (including
amino acid)
• Neuroactive peptides (short polymers of
amino acids)
• Soluble Gases
 Klasifikasi (3)
Small Molecule Neurotransmitter Substances
Acetylcholine (ACh) Dopamine (DA) Norepinephrine (NE)
Serotonin (5-HT) Histamine Epinephrine

Amino Acids
Gamma-aminobutyric acid (GABA) Glycine Glutamate
Aspartate

Neuroactive Peptides - partial list

bradykinin beta-endorphin bombesin calcitonin
cholecystokinin enkephalin dynorphin insulin
gastrin substance P neurotensin glucagon
secretin somatostatin motilin vasopressin
oxytocin prolactin thyrotropin angiotensin II
sleep peptides galanin neuropeptide Y thyrotropin-releasing hormone
growth hormone-releasing
gonadotropnin-releasing hormone luteinizing hormone vasoactive intestinal peptide
hormone

Soluble Gases
Nitric Oxide (NO) Carbon Monoxide
Somatic Nervous System vs
Autonomic Nervous System

The Differences??
 Acetylcholine

•Synthesis and degradation

•Receptors

•Neuromuscular junction disorders

 Sintesis Asetilkolin

Choline Acetyltransferase (ChAT)

Acetyl CoA + Choline Acetylcholine + CoA

+ CoA
Degradasi Acetylcholine

 Beraksi pada reseptor yang tersebar pada

pascasinaptik dan presinaptik
 Degradasi menjadi kolin dan asetat oleh
enzim kolinesterase
 Reuptake ke ujung presinaptik dalam
bentuk kolin  digunakan kembali untuk
sintesis
Acetylcholine Synthesis and Degradation
PDH complex
(FAD, lipoamide, TPP)
Pyruvate Acetyl-CoA + choline

Choline acetyltransferase
(CAT)
(inhibited by mercurials) Reuptake
or diet
Acetylcholine
Acetylcholinesterase (AChE)
(membrane associated; inhibited by
nerve agents, sarin)
Acetate + choline
 Acetylcholine
Receptor

 An integral membrane protein that responds

to the binding of acetylcholine
 Classified into :
 Nicotinicacetylcholine receptors
 Muscarinic acetylcholine receptors
 Acetylcholine Receptor
AChR
a

b
ACh
g (or e)

ACh
d
a
Miyazawa, A., Y. Fujiyoshi, and N. Unwin. 2003. Structure and gating
mechanism of the acetylcholine receptor pore. Nature 423:949-955.
Acetylcholine Receptor

http://www.med.upenn.edu/ins/faculty/lindstro.htm
Jon M. Lindstrom, Dept Neuroscience
School of Medicine, University of Pennsylvania
 Nicotinic Receptor
 Protein pentamer terdiri dari lima subunit :
α2, β, γ, δ
 Ada di neuromuscular junction, ganglia
otonom, medula adrenal, dan SSP
 Muscarinic Receptor

 Reseptor terhubung dengan G-protein.

Terdiri atas 5 sub tipe
 M1, M3, M5 terhubung dengan Gq protein
 M2, M4 terhubung dengan Gi protein.
 Ada di otak, sistem saraf otonom
(parasimpatik)
Regulation of Acetylcholine
 Up and Down Regulation
Epinefrin dan Norepinefrin

 Golongan katekolamin
 Berikatan dengan reseptor adrenergik
Sintesis Epinefrin dan Norepinefrin
Degradasi Epinefrin dan Norepinefrin
Reseptor Adrenergik

 Reseptor terkopling G Protein

 Tersebar di jantung, pembuluh
darah, otot polos, intestine, uterus
dan lain-lain
 Reseptor :
- Tipe Alfa  α1, dan α2
- Tipe Beta  β1, β2, β3
Reseptor Alfa
 Tujuh heliks transmembran
 Dibagi subtipe : α1, dan α2
 Reseptor α1 : otot polos, jantung,
hepar
 Reseptor α2 : otot polos vaskuler,
ujung saraf, islet pankreas
 Reseptor Beta
 Tujuh daerah hidrofobik yang tertanam di
membran masing-masing terdiri dari 20-24
asam amino.
Terima Kasih