BIOKIMIA SYARAF DAN OTAK

Biochemistry Department
Hasanuddin University
 SUBTOPIC
 STRUCTURE OF A NERVE CELL
 ENERGY METABOLISNM 0F BRAIN
 AMINO ACID METABOLISM OF BRAIN
 NEUROTRANRSMITTER
 SYNAPSES
 CLINICAL APLICATION
  Soma ( Badan sel): T4 keluarnya dendrit
dan akson
N
 Dendrit: : menerima ransang
 Akson : meneruskan ransang
 Sel-sel Schwan: sel bermielin
merupakan isolator listrik yg
mengelilingi akson
 Sinaps: Tempat pemindahan rsg dan
menghubungkan antara satu neuron dgn
lainnya
 Neuronal Structure

PSY4080 6.0D Neurotransmitter Function 13

 Metabolisme energi  Otak
 Glukosa satu2nya pemasok energi
 Keadaan lapar: Benda2 keton
 Cadangan glikogen sgt sedikit
 Asam lemak terikat albumin tdk dpt
melalui sawar otak
 Asam amino tdk dpt menghslkan ATP
tdk mampu glukoneogenesis
 Rx terptg perlu energi : pemecahan ATP
utk mentranspor Na+/K+
Metabolisme energi  Otak
Metabolisme Asam Amino Otak
 Otak  metabolisme. as amino yg aktif
 Konsentrasi intraseluler sangat tinggi
 Glutamat (5-10 mM) & aspartat(2-3 mM)
 GABA (gamma aminobutirat): pintasan ini
khas utk otak
 Glisin, aspartat,gutamat & GABA
substansi .transmitor
 Neurotransmitter: subs. sinyal kimia yg
disekresi  neuron sebelahnya / sel2 saraf
Metabolisme Asam Amino Otak
 NEUROTRANRSMITTER

 Sel saraf mengatur organisme melalui

subs. kimia: neurotransmitter &
neurohormon
 Neurotrasmitter: disekresi ke dlm celah
sinaps, jangkauan sempit, efektipitas
pendek
 Neurohormon: disekresi ke dlm
darah,jangkauan lbh luas, epektifitas
panjang
 LIFE CYCLE OF A TRANSMITTER

Stages 1 & 2 Accumulation of a precursor amino acid into the neuron which is metabolized to yield
the mature transmitter (ZZ)
Stage 3 Transmitter is then accumulated into vesicles by the vesicular transporter for storage
and release.
Stages 4 & 5 Transmitter is released into synaptic cleft to interact with post-synaptic receptors or
autoreceptors that regulate transmitter release, synthesis or firing rate.
Stage 6 – 9 Inactivation and termination of the action of the released transmitter by reuptake through
neuronal transporter proteins, enzymatic degradation, uptake by glial cells or passive
diffusion
Neurotransmitter & Neurohormon
 Substances that can be considered possible
Neurotransmitters or Neuromodulators
Table 2.
Biogenic amines
• acetyl choline • Other primary amines
• Catecholamines : Histamine
Dopamine* Octopamine
Norepinephrine* Phenylethylamine
Epinephrine* Phenyletahanolamine
• 5-hydroxytryptamine
= serotonin*
• Polyamines
Putrescine
Spermine
Spermidine
Amino acids Purines
Glutamic acid* Adenosine Guanin
Aspartic acid ATP, etc
Glycine
Α-aminobutyric acid*
= GABA
Taurine
Proline
Neuropeptides
Substance P Enkephalin
Carnosine Angiotensin I
Thyrotropin-releasing hormone Angiotensin II
(TRH) Oxytocin
Neurotensin Vasopressin
Somatostatin Cholecystokinin
β-endorphin Bradykinin

(De Robertis: 690).

Acetylcholine
Glutamate Aspartate
GABA Regarded as Taurine Possible candidate
Glycine Established A large number transmitters
Norepinephrine transmitters of peptides
Dopamine
Serotonin
Nor epinephrine Sometimes called
Dopamine Neuromodulators
Serotonin rather than
Various neuro Neurotransmitters
peptides
Some of the Neurotransmitters found in Nervous Tissue.
EXCITATORY :
Acetylcholine,
Aspartate, Dopamine,
Histamine,
Norepinephrine,
Epinephrine,

ATP, glutamate,
5hydroxytryptamine.

INHIBITORY : GABA,
Glycine

(Devlin : p.931)
 Biosintesis katekolamin
1. Tirosin menghslkan dopa
2. Dopa menjadi dopamin

3. Dopamin dihidroksilasi menjadi

noradrenalin
4. Noradrenalin dimetilasi menjadi
adrenalin/ epinefrin
Dopamin, noradrenalin & adrenalin:
NeuroTransmitter
Adrenalin, noradrenalin: hormonal.
Biosintesis Katekolamin
 Kriteria Neurotransmitter
 Merupakan produk neuron
 Disimpan dalam sinaps
 Disekresi dlm celah sinaps bila ada rsg
 Terikat pd reseptor spesifik memb.pasca
sinaptik pd neuron lain atau sel otot dan
mempgrh aktivitasx melalui pengaturan
aliran ion
 CLASSICAL NEUROTRANSMITTERS

Amino acids
γ- Aminobutyric acid
Glycine
Glutamate

Acetylcholine
 STRUKTUR KIMIA
NEUROTRANSMITTERS
AMINO ACID NEUROTRANSMITTERS
INHIBITORY AMINO Glutamic acid
ACIDS - GABA (and decarboxylase
Glycine)Widespread (GAD) converts
distribution in the glutamate to GABA
CNS Mediate fast
and slow neuro-
transmission
 CATECHOLAMINE
Synthesis & Storage

Characteristics of a norepinephrine
(NE)-containing catecholamine neuron.
Tyrosine (Tyr) is accumulated by the
neuron and is then metabolized
sequentially by tyrosine hydroxylase (TH)
and L-aromatic amino acid decarboxylase
(L-AADC) to dopamine (DA).
The DA is taken up through the vesicular
monoamine transporter into vesicles. In DA
neurons, this is the final step.

However, in this NE-containing cell, DA is

metabolized to NE by dopamine-b-
hydroxylase (DBH), which is found in the
vesicle.

Once NE is released, it can interact with

postsynaptic noradrenergic receptors or
presynaptic noradrenergic autoreceptors.
Monoamines
(Biogenic amines)
Dopamine
Norepinephrine
Epinephrine
Serotonin
Histamine
 Key Biosynthetic Enzymes
TRANSMITTER ENZYMES ACTIVITY

Amino acids
γ-Aminobutyric acid Glutamic acid decarboxylase Specific
Glycine Enzymes operating general metabolism Specificity undetermined
Glutamate Enzymes operating general metabolism Specificity undetermined

Biogenic amines
Dopamine Tyrosine hydroxylase Specific
Norepinephrine Tyrosine hydroxylase & Specific
dopamine β-hydroxylase
Epinephrine Tyrosine hydroxylase & Specific
dopamine β-hydroxylase
Serotonin Tryptophan hydroxylase Specific
Histamin Histidine decarboxylase Specificity undetermined

Acetylcholine Choline acetyltransferase Specific

 MEKANISME KERJA

• NM dan NH terikat pad reseptor pasca snp

• Sbg >> reseptor mengatur kanal2 ion secar tdk
lsg melalui protein P / ligan
• Misalx: reseptor nikotinik utk astilkolin, GABA
dan glisin
• Membuka kanal>>> menutup
PSY4080 6.0D Neurotransmitter Function 36
IONIC ACTIONS OF NEUROTRANSMITTERS
NEUROTRANSMITTERS & DISEASE

 ACh Mysthesia Gravis,

Alzheimer’s disease
 Dopamine Parkinson’s Disease
 Serotonin Depression
 Glutamate Excitotoxicity
 following stroke
 STROKE
 STROKE : Berkurangnya aliran darah
(KERUSAKAN OTAK TERLOKALISIR)
- Paralisis
- Kebutaan
- G3 kemampuan bicara
- Hilangnya kesadaran permanen
Patomekanisme:
Tromboembolik arteri. serebri  pasokan O2
dan glukosa menurun  kerusakan otak
 Proses Kerusakan Otak Trombosis Serebri

1. Induksi: Iskemia menyebabkan depolarisasi

memb. neuron  pelepasan Glutamat uk
Ca2+ eksitasi  aliran masuk Ca2+ dan Na+
>>>  kematian sel
2. Amflifikasi:Pelepasan tambahan glutamat 
eksitasi lanjut keneuron sebelahnya
3. Ekspresi: Kadar Ca 2+ >> vasokonstriksi 
trombosis memburuk ( glutamate cascade)
- produksi radikal bebas
 Penyakit Parkinson
 Defisiensi Dopamin dlm Substansia
Nigra dan Korpus Striatum
 Akibat dari degenerasi sel yang

mensintesis dan menggunakan dopamin

( dopaminergik)
 Proses kerja dopamin

1. Sintesis dopamin dari tirosin yang

dikatalisis oleh tirosin hidroksilase
2. Penyimpanan dopamin dalam vesikel
sinaps
3. Pelepasan dopamin scr eksositosis
4. Pengikatan dopamin pd reseptor
postsinaps
5. Pengambilan kembali dopamin
6. Penguraian dopamin dlm celah sinaps/
setelah sinaps pengambilan kembali dlm
terminal presinaps
R/ a. Antikolinergik
b. Prekursor Dopamin
c. Agonist Reseptor Dopamin
Fig. 11. Schematic diagram illustrating the release of dopamine by a neuron in
the substantia nigra and also showing the sites of action of drugs that
ameliorate or induce parkinsonism.
 Penyakit ALZHEIMER

 Proses degeneratif  Apoptosis 

( korteks serebri dan hipokampus)
Mikro: penimbunan plak amiloid beta
protein
perubahan neurofibriler & vaskuler
 Plak amiloid  neurotoksik  >> ion

Ca2+ intrasel  hiperfosforilasi dan

pembtk filamen helix berpsg pd simpul
neurofibriler
 Genetik  Alzheimer
 Mutasi gen amyloid precursor protein
(Kr 21) 
 Proteolisis APP  fragmen A beta
Protein
 Deposisi A beta P  >> kdr Ca 2+ 
mengaktifkan protein kinase  filamen
heliks kekacauan neurofibriler
 Deposisi A beta P dan hiperfosforilasi
meenahun  plak & kekacauan
neurofibriler  demensia & intelektual
<<<
 Penyebab lain Alzheimer
 Penurunan kolin asetiltransferasan &
Ach
 Pe>> almunium dlm plak

 R/ obat spesifik belum ada

 SKIZOFRENIA
 Abnormalitas struktur lobus
temporalis medialis dan pelebaran
ventrikulus otak
 Hiperdopaminergik

 kategori
1. Kdr Dopamin Otak
2. Metabolik Dopamin
3. dll
 Migrain
 Teori depolarisasi
 Teori vaskuler
 Teori serotinin
 Teori saraf
 Teori saraf + vaskuler
 - trigger stess
 - vasokonstriksi peb. darah
 - Serotonin released
 - Substant P  iritasi srf & vaskuler
 Terima Kasih
&
Selamat Belajar
 Pustaka
 Biokimia Harper
 Atlas Berwarna & Teks Biokimia
 Devlin TH, 1993. Textbook of Biochemistry
with Clinical Correlation 3rd edition. New
York : Wiley-Liss Inc, 931, 937- 938
 Goldstein M, 1983. Biochemistry A Functional
Approach 3rd edition. Tokyo : WB Saunders
Company,650-652, 654, 648