Metabolism in the Brain

8/2/2019 Metabolism in the Brain

1/19

Metabolism of the Brain

Wilson Mandala [email protected]

Department of BiochemistryCOM


2/19

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


3/19

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


4/19

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!!!


5/19

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.


6/19

ATP Production from Glucose

1. Glycolysis

2. TCA Cycle

3. ETC


7/19

Glycolysis pathway

Preparatory Phase

Two molecules of ATPconsumed


8/19

Payoff Phase

four molecules of ATPproduced, net gain of2 ATP molecules


9/19

Tri-Carboxylic Acid (TCA)cycle


10/19

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


11/19

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


12/19

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%


13/19

Livers Role


14/19

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


15/19

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


16/19

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


17/19

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


18/19

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


19/19

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

Documents

Metabolism in the Brain