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Metabolism of the Brain
Wilson Mandala [email protected]
Department of BiochemistryCOM
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Learning objectives
1. Know what the brain uses as itsenergy source
2. List the processes in the brain thatrequire energy
3. Understand what happens in the brain
during starvation
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General Energy Sources
1. Energy required continuouslybut sources available onlyduring meals
2. During and immediatelyfollowing a meal the body goesinto an anabolic state & storesenergy supported by Insulin
3. Between meals, catabolismensues: glycogenolysis,lipolysis, and sometimes proteinlysed to Aas to provide energy
4. Catabolism supported byglucagon and growth hormone
5. In stress or strenuous exercisecortisol increases catabolismrate
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Brain mainly uses Glucose
Glucose is the primary energy substrate for brain and it is
almost entirely oxidized to CO2 and H2O ( total aerobicrespiration)
Although the brain represents only 2% of the body weight,on average it receives:
a. 15% of the cardiac output
b. 20% of total body oxygen consumption
c. 25% of total body glucose utilization
The brain thrives on glucose and oxygen!!!
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Why such high demand for energy?1. To fuel electrical impulses that neurons use to
communicate with each other.
a. About 2/3 of energy is used to help neurons (nervecells) send signals.
b. This requires a continuous passage of Na+, Ca2+ andK+ ions to ensure that neurons can recharge in order tofire the impulses when required. This requires ATPmolecules
2. The remaining 1/3 is used for housekeeping purposes orcell-health maintenance. This helps to keep the brain cellsalive. There is need to maintain a proper ionic balanceinside and outside cells and this requires ATP too. Anyionic imbalances can cause cells to swell leading tostrokes and other precarious conditions.
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ATP Production from Glucose
1. Glycolysis
2. TCA Cycle
3. ETC
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Glycolysis pathway
Preparatory Phase
Two molecules of ATPconsumed
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Payoff Phase
four molecules of ATPproduced, net gain of2 ATP molecules
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Tri-Carboxylic Acid (TCA)cycle
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Other uses of the glucose
Glucose is mainly used as an energy source in thebrain.
A small percentage of the glucose is:
1. incorporated into lipids, proteins, and glycogen forstructural purposes
2. Used as precursor of certain neurotransmitters
such as g-aminobutyric acid (GABA), glutamate,and acetylcholine which are very important in theCNS
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Brain and Glucose The brain is the organ most sensitive to glucose
Brain requires a constant supply of blood glucose Normally glucose is the only energy source for the brain
(can't use fats since fats cannot cross the blood-brainbarrier)
In conditions when blood glucose levels are low(hypogycemia) brain adapts to using other energy richcompounds.
Such conditions include: starvation, DM, low carbs diet,
when diabetic takes too much insulin (insulin shock) Symptoms: mental confusion, slurring of speech ->
coma -> death
Treatment: give glucose
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Regulation of Blood Glucose Levels
Immediately after meals blood glucosecomes from meal
Between meals blood glucose comes from
the liver & kidneys Only the liver and kidneys can release glucose
into the blood
Liver provides 80% of blood glucose supplybetween meals, the kidney 20%
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Livers Role
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Gluconeogenesis
Some molecules can be converted to glucose:
1. Lactate & pyruvate: mainly come from muscles
2. Glycerol: supplied by adipose tissue when
triglycerides are broken down-3. Fatty acids cannot be converted into glucose,
but: Fatty acid metabolism indirectly supportsgluconeogenesis by producing AcetylCoA
4. AcetylCoA activates and inhibits key enzymes,promoting glucose formation
5. Amino acids: 20 of the 22 amino acids can be
converted to glucose through gluconeogenesis
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Glucose supply to brain & other tissues
Delivery of glucose to the blood is controlledby insulin, glucagon and other hormones
Brain receives a constant 80 mg/min(doesn't change much in exercise)
Amount delivered to other tissues dependsupon body state (rest vs exercise)
At rest total glucose output to the blood is about130 mg/min (80 to brain, 50 to other tissues)
During exercise total can increase to about 2500mg/min and this may reduce brain supply
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Alternative energy sources1. Mannose
1. only molecule that can sustain normal brainfunction in the absence of glucose.
2. Can cross the bloodbrain barrier and in two
enzymatic steps is converted to fructose-6-phosphate, intermediate of the glycolyticpathway.
3. However, mannose is not normally present in theblood and cannot therefore be considered aphysiological substrate for brain energymetabolism
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2. Ketone Bodies
1. Under particular conditions, such as starvation, diabetesmellitus, or in breast-fed neonates, plasma levels of theketone bodies (acetoacetate and beta-hydroxybutyrate)increase markedly.
2. Under these conditions, these two ketone bodies can beused by the brain as metabolic substrates.
3. This requires their reverse conversion to acety-CoA whichrejoins the TCA cycle, the resulting NADH and FADH2
joins the ETC producing more ATP molecules
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3. Pyruvate and Lactate
1. Lactate and pyruvate can sustain synapticactivity in vitrobut due to their limitedpermeability across the bloodbrain barrier, theycannot substitute for plasma glucose to maintainfull brain function.
2. if formed inside the brain parenchyma, both
lactate and pyruvate are useful metabolicsubstrates for neural cells
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In starvation (& DM)
1. Low blood glucose levels, supply to brainreduced, ketone bodies used instead
2. Reduction affects brain function, blurred vision,low response to impulses
3. If levels go even lower, subject can go into comaand die
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