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Biochemistry_L1, Brain Metabolism

 L1, Brain Metabolism

Lecture video


Lecture data

_The function unit of brain is called
neurovascular
_The brain uses 20% of the total energy used in the body at rest.
_Neurons use 70–80% of the total energy used by the brain to 

1-restore neuronal membrane potentials following depolarization
2-vesicle recycling
3-neurotransmitter synthesis The remaining is used by glial cells(astrocytes oligodendrocytes & microglia)


Energy sources of the brain


1 . Neurons in the adult brain depend on glucose as an energy source
2 . Ketone bodies are utilized during brain development and in the adult during prolonged fasting periods
3 . Lactate utilization is increased during
intense physical activity

N.B
Due to high metabolic needs & negligible energy stores of the brain, it depends upon continuous influx of substrates from the blood. To protect the brain from fluctuations in t blood composition, the exchange of molecules between blood & CSF is regulated by 2 barriers.

Glucose metabolism by the brain


-Glucose passes from the blood to the brain (through BBB) uptake by different brain cells

Fate of glucose:
1-Glycolysis & lactate formation in the astrocytes
2-Glycolysis & Krebs' cycle in neurons
3-Glycogen synthesis in astrocytes
4-HMP


Glycolysis & lactate formation in the astrocytes:

Astrocytes display a very high glycolytic activity.
Glucose → G-6-P → by glycolysis gives pyruvate.
-Astrocytes contain lactate dehydrogenase-5 (LDH-5) which makes lactate from pyruvate (pyruvate → lactate).
-Most astrocytic lactate is obtained from anaerobic metabolism of glucose and small amounts from G-6-P obtained from glycogenolysis.
-Astrocytic lactate is used as a source of energy for neurons

 Glycolysis & Krebs' cycle in neurons

Neuronal metabolism seems to be oxidative. Glucose → G-6-P → by glycolysis gives pyruvate.

Neurons contain lactate dehydrogenase-1 (LDH-1) which preferably catalyze the 
production of pyruvate.

Pyruvate → Acetyl COA → Krebs cycle → Energy

Glycogen synthesis in astrocytes

Brain has low amount of glycogen, which is found in astrocytes.Glucose enters the astrocytes via GLUT1 and possibly the insulin-sensitive GLUT4. Glucose is phosphorylated by hexokinase(HK)to G-6-P → G-1-P by phosphoglucomutase (PGM) → UDP glucose by UDP glucose pyrophosphate (UDPGPP). The UDP glucose → glycogen synthesis via the actions of glycogen synthase (GYS). Glycogenolysis: Glycogen is broken down by glycogen phosphorylase (GP)

HMP shunt

Glucose may be oxidized via HMP shunt, highly important not only for neurons but also for many other brain cells. This pathway contributes to the production of NADPH and 5-carbon sugar.
NADPH + H+ is reducing agent important for: Synthesis of lipids and nucleic acids. Therefore, HMP shunt is of great importance in a developing brain compared to a mature brain ( lipogenesis and myelination in the nervous system).

Metabolizing neurotransmitters, as well as aldehydes and peroxides. In this way, NADPH also promotes regeneration of antioxidant glutathione (GSH). Therefore, high HMP shunt activity can also be found in the mature brain

Ascorbic acid released by astrocytes is taken up by neurons to protect themselves from oxidant species (ascorbic acid is oxidized in neurons). Oxidized ascorbic acid (dehydroascorbic acid) is released from neurons and taken up by astrocytes.
Oxidized ascorbic acid is reduced via NADPH+H+ to ascorbic acid.

Lactate metabolism by the brain

Neurons synthesize energy by oxidative
 metabolism of glucose (Krebs cycle & respiratory chain) using glucose as a fuel.
Neurons also can utilize lactate ( preference of lactate if both are present).
Neurons exhibit a slower rate of glycolysis than astrocytes due to: low production of fructose-2,6-bisphosphate, which is the strongest activator of phosphofructokinase, a key enzyme of glycolysis. Excessive activation of glycolysis in neurons leads to

oxidative stress and apoptosis of neurons. This suggests

that neurons cannot afford to maintain a high rate of glycolysis. At the same time, it has been shown that ↑ glucose concentration starts the HMP shunt in neurons.

MCQ


1-all of the following are function of neuron except:
a-restore membrane potentiale
b-vesicle recycling
c-depolarization
d-neurotransmitter synthesis

2-neurons use ........of brain energy:
a-50-60
b-70-80
c20-30

3-which of the following has high glycolytic activity:
a-microglia
b-oligodendrocyte
c-astrocyte
d-neurons

4-which of the following makes lactate from pyruvate and
which catalyze the production of pyruvate:
a-lactate dehydrogynase 1
b- lactate dehydrogynase 5

5-neurons exhibit higher rate of glycolysis than astrocyre( )

6-which of the following is keton body:
a-3-β-hydroxybutyrate
b-acetoacetate
c-acetone
d-all of the following

answers:
1-c
2-b
3-c
5-false
6-d
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