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Pendahuluan
Metabolisme otak
Neurotransmitter
Clinical applications
Neuronal Structure
Sinaps:
celah, t4
endrit: menerima
rangsang
pemindahan rsg;
penghubung
antar
neuron
Sel-sel
Schwan:
sel bermielin
merupakan isolator listrik yg
mengelilingi
akson
Soma (Badan
sel): T4
keluarnya dendrit dan
akson Akson: meneruskan rangsang
PSY4080 6.0D
Neurotransmitter Function
Transport of Glucose
GLUT1 (55 kd form):
localized in microvessels of the blood-brain barrier.
glial cells.
Metabolisme Otak
Laju respirasi sangat tinggi
Massa ~2% dari total: konsumsi O2 ~ 20%
Hypoglycemia
Hypoglycemia: plasma glucose conc below 50 mg/dL
76 -72 mg/dL suppression of insulin secretion
~67 mg/dL counterregulatory hormones
Conservative definition: plasma glucose <75 mg/dL
pada otak
Glisin, aspartat, gutamat & GABA penting
sebagai bahan baku
Neurotransmitter: substansi sinyal kimia
yang disekresi (dari neuron ke neuron/organ
target)
Ammonia toxicity:
NH3 + 2OG + NADH Glu + NAD+
Krebs cycle impairment: 2-OG depletion
Glu excess, excitotoxicity
Ammonia handling
Clinical consequences: liver disease impairs
brain function
principle: insufficient urea synthesis NH3
accumulationneurotoxicity
Hepatic encephalopathy: gr.I-IV
Fulminant liver failure (i.e. paracetamol
poisoning) threatens live also by ICP
NEUROTRANSMITTER
Antarsel
saraf terdapat celah impuls
CHEMICAL SYNAPSES
NEUROTRANSMITTERS
5 criteria defining neurotransmitters
1) Synthesis of transmitter substance in the neuron
2) Storage of neurotransmitter or precursor in the
presynaptic nerve terminal
3) Release of the neurotransmitter into the synaptic
cleft to bind to target receptors on the postsynaptic
membrane resulting in specific change in activity
4) Mechanism of removal of transmitter from the
synaptic cleft
5) Exogenous application of neurotransmitter mimics
the
action of endogenously released 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 postsynaptic 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,
Table 2.
Biogenic amines
acetyl choline
Catecholamines :
Dopamine*
Norepinephrine*
Epinephrine*
5-hydroxytryptamine
= serotonin*
Amino acids
Glutamic acid*
Aspartic acid
Glycine
-aminobutyric acid*
= GABA
Taurine
Proline
Enkephalin
Angiotensin I
Angiotensin II
Oxytocin
Vasopressin
Cholecystokinin
Bradykinin
(De Robertis: 690).
Acetylcholine
Glutamate
GABA
Glycine
Norepinephrine
Dopamine
Serotonin
Regarded as
Established
transmitters
Aspartate
Taurine
A large number
of peptides
Possible candidate
transmitters
Metabolism dopamine
1. Dopamine Synthesis from tyrosine
that
catalyzed by tyrosine hydroxylase
2. Dopamine storage in synaptic
vesicle
3. Dopamine release by exositosis
4. Dopamine binding to the
postsynaptic
receptor
5. Dopamine reuptake
Biosintesis Katekolamin
PSY4080 6.0D
Neurotransmitter Function
35
PSY4080 6.0D
Neurotransmitter Function
36
Mysthesia Gravia,
Alzheimers disease
Dopamine
Parkinsons Disease
Serotonin, NE
Depression
Glutamate
Excitotoxicity following stroke
Cholinergic system
(Acetylcholine)
Dopaminergic system
(Dopamine)
Noradrenergic system
(Norepinephrine)
Glutamate
Excitotoxity = excesive Glu release
epilepsy, traumatic brain injury
Na+ and Ca2+ IC accumulation
swelling
GABA
Inhibitory
STROKE
STROKE : Berkurangnya aliran darah
Penyakit Parkinson
Defisiensi Dopamin dlm Substansia
Penyakit ALZHEIMER
Proses degeneratif Apoptosis
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
Ach
Pe>> almunium dlm plak
SKIZOFRENIA
Abnormalitas struktur lobus
Migrain
Teori depolarisasi
Teori vaskuler
Teori serotinin
Teori saraf
Teori saraf + vaskuler
- trigger stess
- vasokonstriksi peb. darah
- Serotonin released
- Substant P iritasi srf & vaskuler
dopamine
transporters
Terima Kasih
&
Selamat Belajar
Pustaka
Biokimia Harper
Atlas Berwarna & Teks Biokimia
METABOLIK ENSEFALOPATI
KOMA
BRAIN DEATH
TENSION HEADACHE
MIGRAINE
CRANIAL ARTERITIS
TRIGEMINAL NEURALGIA
CLUSTER HEADACHE
TIA
CEREBRAL INFARCTION
INTRACEREBRAL HEMATOMA
SUBAR