The Nervous Tissue: (best represented by the brain)
Functions: The transmission of electric impulses.
Cell types: 1. Neurones (the excitable nerve cells responsible for nerve impulses
transmission).
2. Glia (non-excitable).
The neurons are heterogenous in shape (pyramidal, stelate, bipolar).
General features: - Cell body (Perikaryon)
- Large nucleus, with defined nucleolus.
The perikaryon contains other structures: ribosomes, smooth/ rough E.R mitochondria.
- Dendrites: processes formed from plasma membrane.
- The axon: long, thin, ocassionally branched process, wrapped in a nyelin sheath
interrupted by breaks (nodes of Ranvier).
The Glial cells are smaller than neurones.
Functions: - Investing axons with myelin sheath.
- Provide nutritional/metabolic support for neurons.
- Excretion of waste-products to CSF.

Neurones commmunicate with each other by chemical means via synapses.

The nerve ending contains vesicles accumulate the neurotransmitter, and
mitochondria.
Chemical Composition:
1. Lipids: high content and unique structure (>50% of total solids)
Lipid in: Myelia: 80%
W. Matter: 60%
G. Matter: 40%
Phospholipids (40%), glycolipids (~35%), cholesterol (~ 20%), and sulpholipids.
No true fat is present in nervous tissue.
Cholesterol: ≃ 25% of body cholesterol is present in N.T.
is readily synthesized in brain especially the young growing child.
has a low rate of breakdown (turnover).
Phospholipids: PC, PI, have high turnover rate.
Fatty acids: majority are unsaturated with high c-chain (as high as 24c) synthesis: in
situ. Low rate of breakdown.
Important functions of Lipids:
- Insulating myelin sheath and protective layer (nerve impulse travels at 3-120 m/s).
- Cellular membrane functions. No metabolic role found.
Multiple sclerosis: loss of myelin sheath (marked dysfunction of N.T.).
2. Proteins: - 47% of dry matter of brain consists of proteins.
- The gray matter is much richer in proteins than white matter.
important ones:
A. S-100 (highly acidic protein): high level in glial cells and small level in neurones.
- 30% of a.a. residues are: Asp and Glu.
- 3 p.p. chains (non-identical)
- high affiinity towards Ca2+.
B. 14-3-2 Acidic protein: identified as enolase isoenzyme.
2-P-glycerate
enolase
PEP
function of acidic proteins: implicated with the memory or learning ability of
brain.
C. Calmodulin: found in brain, thought to be involved in Ca-dependent release of
acetylcholine and nor-epinephrine from their vesicular stress.
D. Neurokeratin: resistant to enzymatic degradation. It resembles epidermal keratin
in physical properties but differ in a.a composition.
Other proteins mainly found in Myelin:
E. Basic protein: 18 k.d., constitutes 30% of total myelin proteins with high content
of Arg residues.
F. Proteolipid: lipid + protein
hydraphobic a.a. residues.
Other proteins include: Albumin, several globulins, a nucleoprotein.
Notes: 1. Brain proteins have a rapid turnover rate relative to other body proteins.
2. Nerve tissue has a unique criterion in retaining and reutilizing NH4+.
3. Nerve tissue has all the urea cycle enzymes.
4. The percentage of nitrogen in brain proteins is rather low. 13.4%.
5. Because of the relative impermiability of “blood-brain barrier,” lipids and
proteins are well retained and reutilized by the brain which explains the
resistance of brain deterioration during prolonged starvation. The brain is
the only tissue in which the breakdown products of lipids and proteins are
exclusively reutilized.
3. Carbohydrates: very little. Glucose and glycogen are present in small amounts.
Glucose is exclucively used for energy production (glycolysis + TCA cycle +O2).
Lack of O2/glucose can rapidly lead to brain dysfunction, come or death.
Hypoglycemia is associated with mental confusion, dizziness, convulsions or loss
of consciousness. ATP is required for maintenance of transmembrane potentials
and for the biosynthesis of proteins and neurotransmitters. Abnormal carbohydrate
metabolism may lead to certain neurosis. Patients with anxiety neuroses have
excessively high blood lactate level.
4. Neuropeptides: brain/CNS tissues
- The releasing hormones of hypothalamus and somotostatin.
- The “enkephalins” (inhibitory meurotransmitters): inhibit α denylate cyclase and
cAMP formation from ATP (necessary for certain brain function).
- The “endorphins” (12-100x more potent than enkephalin): are derived from
β-lipoprotein (present in anterior pituitary) which is a 91- residue long. Three types:
α, β and γ-endorphins. More recent 24 compounds were discovered (All classified as
neurotransmitters). Substance P (11a.a. residues) involved in pain transmission and
degraded rapidly by peptidases. Y-compound: anxiety-relieving neuro-transmitter.
- Nerve growth factor (NGF): insulin-like peptide, binds to specific protein receptor
on nerve cells, therefore, stimulating rapid growth of nerve cells. Two identical A and
B p.p.c. of 118 residues complexing with 2 other proteins for activating NGF.
The Biochemistry of Neurotransmission:
Two types: chemical and peptide neurotransmitters.
Chemical meurotransmitters: more than 30 have been described. Most of them are low
M.W. compounds containing a positively charged N-atom. Each chemical
neurotransmittor exhibits excitatory or inhibitory effect.
Criteria for Neurotransmitters identification:
1- Compound should be synthesized and/or stored in the nerve endings (sites of
release).
2- It should be released upon pre-synaptic stimulation.
3- It should mimic the action of its presynaptic stimulation when applied
postsynaptically.
4- It must have antagonists to prevent its effect.
5- There should be a mechanism available to terminate its effect.
Therefore, the categories of neurotransmitters are classified according to the extent
which all of the above criteria have been fulfilled. For example, acetylcholine is
categorized as first division neurotransmitter while glu/ATP second division and TRH
third division.
The transmission of nerve along neural axons is an electrical phenomenon. However,
between nerve cells (synaptic gap is too large (20nm) for electrical transmission to
take place) the transmission is a chemical one.
Examples of Chemical Neurotransmitters:
1. Acetylcholine
Biosynthesis: Choline is derived from “acetylcholine” after its hydrolysis by
acetykcholinesterase or from the circulation. It is taken up into neurone by a high
affinity, Na+- dependant, ATP requiring process. It is co-transported with Na+, and
ATP is required to “pump” Na+ cations out of the neurones.
 This is a rate-limiting step for acetylcholine by: choline acetyl transferase.
- Acetyl COA comes from citrate cleavage into acetyl COA + OX.A.A. It reacts with
choline to form acetylcholine by: Choline acetyl transferase.
- The acetylcholine formed is taken in vesicles where it accumulates to 880mh
(energy is required depending on a pH gradient). In addition, ATP (100mM) which
itself can act as a 2nd division neurotransmitter and Ca2+ are also stored.
Release of Acetylcholine: Signal at nerve terminal causes CA2+ channels to open, then
fusion of resicles with plasma membrane followed by release of vesicle contents
(other mechanisms may exist).
Termination of Action: acetylcholine is hydrolyzed rapidly into choline and acetic
acid by acetylcholinesterase. This enzyme is present in both past and pre-synaptic
membranes and anchored by a collagen-like triple-helical tail.
2. Glutamate and GABA
In glutamate neurones: - 80% of glu released at nerve endings is derived from
Gln
Glnase
Glu, the remainder (20%) comes from “Glu” catabolism.
(TCA cycle).
- Glu is released from neurones upon nerve stimulation.
- Re uptake of “Glu” by glutamate neurone and glial cell: an energy dependent and
Na+- requiring process.
- In the glial cell: glu
gln - synthetase
gln (Inactivation)
In GABA (inhibitory neurotransmitter) neurones:
- Gln from glial cell/CSF passes to GABAergic neurone, to be converted to glutamate;
then;
- Glu
GABA-decarboxylase
(pyridoxal-P)
GABA
Stimulated by valporic acid ?
- GABA
is released from its neurone upon nerve stimulation.
- Reuptake: similar to glu reuptake.
* - GABA is converted to succinate semialdehyde (SSA) by
GABA transferase 2-oxoglutarate aminotransferase (pyridoxal-P)
Inhibited by valporic acid.?
- SSA
DH
succinate
2 α KG (Inactivation)
- Valporic acid increases brain/cerebellum levels of GABA.
Noradrenaline and Dopamine
- Noradrenaline (nor-ephinephrine) serves as a stimulating neuro-transmitter for most
postganglionic fibers of sympathetic nervous system and certain areas of CNS:
(Adrenergic fibers).
Synthesis: last year course: Note: 1-Release of nor-ephinephrine from vesiclesat the
end of pre-synaptic adrenergic fibers requires external Ca2+. 2- The reuptake: Na+
requiring and ATP-dependant.
- Dopamine: inhibiting neurotransmitter. Deficiency of dopamine was found in brain
tissue of patients with Parkinson’s Disease.
Inactivation: By two main enzymes (Catecholamine O-methy transfer are (COMT)
and monoamine oxidose (MAO), also Alcohol DH & aldehyde DH.
catecholamine
catecholaldehyde
3-O-CH3-catecholamine
ALD
3-O-CH2-catechol aldehyde
Catechol acid
AD- Alcohol DH
ALD- Aldehyde DH
3-O-CH3- catechol acid
Types of Neurotransmitters Receptors|:
Intrinsic plasma membrane proteins located usually post- synaptically or in some
cases pre-synaptically.
1. Ionotrophic: (have ion-specific gating channel)
Example: Acetyl-binding to the nicoticin cholino-receptor causes conformational
changes in the channel, leading to inward movement of Na+ ions. This causes
membrane depolarization (less negative membrane potential)
excitation of axon
(referred to as excitatory post synaptic potential (EPSP)).
On the other hand, binding of the neurotransmitter at its metabotrophic site results in
a change of intracellular metabolism. (c.f. binding of peptide hormones to their
receptors). One of the two membrane enzymes is activated:
adenylate cyclase or phospholipase C. Thus:
Diacylglycerol-P
P-Inositol
Diacylglycerol
Inositol-triphosphate
ATP
Adenylate
Cyclase
CAMP
+
+
Protein kinase C
(inactive)
PKC
(active)
PKA
(inactive)
PKA
(active)
Phosphorylation of channel protein (membrane hyperpolarization)
allowing the opening of the channel
Myasthenia gravis:
influx of ions (K+/Na+/Cl-).