Page 365 - Color Atlas of Biochemistry

P. 365

356 Tissues and organs

Metabolism B. Glutamate, glutamine, and GABA
The proteinogenic amino acid glutamate
The brain and other areas of the central ner-
vous system (CNS) have high ATP require- (Glu) and the biogenic amine 4-aminobuty-
rate derived from it are among the most im-
ments. Although the brain only represents
about2% of the body’s mass,itconsumes portant neurotransmitters in the brain (see
p. 352). They are both synthesized in the
around 20% of the metabolized oxygen and
ca. 60% of the glucose. The neurons’ high en- brain itself. In addition to the neurons, which
use Glu or GABA as transmitters, neuroglia are
ergy requirements are mainly due to ATP-de-
+
+
pendent ion pumps (particularly Na /K AT- also involved in the metabolism of these sub-
Pase) and other active transport processes stances.
Since glutamate and GABA as transmitters
that are needed for nerve conduction (see
p. 350). must not appear in the extracellular space in
an unregulated way, the cells of the neuroglia
(center) supply “glutaminergic” and “GABAer-
A. Energy metabolism of the brain gic” neurons with the precursor glutamine
(Gln), which they produce from glutamate
Glucose is normally the only metabolite from
which the brain is able to obtain adequate with the help of glutamine synthetase [1].
amounts of ATP through aerobic glycolysis GABA neurons (left) and glutamate neu-
rons (right) initially hydrolyze glutamine
and subsequent terminal oxidation to CO 2
with the help of glutaminase [1] to form glu-
and H 2 O. Lipids are unable to pass the blood– tamate again. The glutamate neurons store
brain barrier, and aminoacids are alsoonly
available in the brain in limited quantities this in vesicles and release it when stimu-
lated. The GABA neurons continue the degra-
(see B). As neurons only have minor glycogen dation process by using glutamate decarbox-
reserves, they are dependent on a constant
supply of glucose from the blood. A severe ylase [3] to convert glutamate into the trans-
mitter GABA.
drop in the blood glucose level—as can occur
Both types of neuron take up their trans-
after insulin overdosage in diabetics, for ex- mitter again. Some of it also returns to the
ample—rapidly leads to a drop in the ATP level
in the brain. This results in loss of conscious- neuroglia, where glutamate is amidated back
ness and neurological deficits that can lead to into glutamine.
Glutamate can also be produced again from
death. Oxygen deficiency (hypoxia) also fint
affects the brain. The effects of a brief period GABA. The reaction sequence needed for this,
known as the GABA shunt, is characteristic of
of hypoxia are still reversible, but as time the CNS. A transaminase [4] first converts
progresses irreversible damage increasingly
occurs and finally complete loss of function GABA and 2-oxoglutarate into glutamate and
succinate semialdehyde (–OOC–CH 2 –CH 2 –
(“brain death”). +
During periods of starvation, the brain after CHO). InanNAD -dependent reaction, the
a certain time acquires the ability to use ke- aldehyde is oxidized to succinic acid [5],
from which 2-oxoglutarate can be regener-
tone bodies (see p. 312) in addition to glucose
to form ATP. In the first weeks of a starvation ated again via tricarboxylic acid cycle reac-
tions.
period, there is a strong increase in the activ-
The function of glutamate as a stimulatory
ities of the enzymes required for this in the transmitter in the brain is the cause of what is
brain. The degradation of ketone bodies in the known as the “Chinese restaurant syndrome.”
CNS saves glucose and thereby reduces the
breakdown of muscle protein that maintains In sensitive individuals, the monosodium glu-
tamate used as a flavor enhancer in Chinese
gluconeogenesis in the liver during starva-
tion. After a few weeks, the extent of muscle cooking can raise the glutamate level in the
braintosuchanextent that transient mild
breakdown therefore declines to one-third of neurological disturbances can occur (dizzi-
the initial value.
ness, etc.).

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