Brain Metabolism (Finished) Flashcards
What are the major pathways for energy metabolism in the brain?
glycolysis, tricarboxylic acid/krebs cycle, also keytone bodies for neonates or starvation, also lactate
a. The neuron uses most of the ATP compared to glial cells.
i. Used for (most to least): synaptic transmission, housekeeping, action potential, resting potential, Ca2+ entry and vesicle recycling, NT recycling.
What is the role of brain glycogen?
energy
making up macromolecules like glycolipids or glycoproteins
synthesis of NTs like glutamate, GABA, and ACH
a. Stored in the astrocytes and used by the brain when it needs extra glucose (reserve) in situations such as stroke, drowning, suffocation. Only provides 4-6 minutes
What are the key regulatory sites in brain glucose metabolism?
In glycolysis it is regulated by hexokinase, phosphofructokinase and pyruvate kinase.
TCA is regulated by pyruvate dehydrogenase, isocytrate dehydrogenase, and alpha ketoglutarate dehydrogenase.
For each mole of glucose consumed by the brain, how much is converted to lactate under aerobic conditions? Under anaerobic (stroke) conditions?
a. Complete oxidation of 1 mol of glucose requires 6 moles of O2 but this doesn’t happen b/c some of the glucose is converted to lactate.
b. Under normal conditions 1/6 of a mol of glucose is converted to lactate under aerobic conditions
c. Under anaerobic conditions all of it Is converted to lactate
Are there alternative pathways of glucose metabolism?
It can go to the pentose phosphate shunt to produce NADPH which is needed for nucleotide biosynthesis and glutathione.
It can go to produce glycogen.
How is brain metabolism of any substrate measured?
CMR-G = (A-V)F/W A=arterial conc.(mole/l) V=venous conc.(mole/l) F=blood flow (l/min) W=weight (g) CMR Units=moles/g/min
If the arterial concentration is higher than the venous than the brain is receiving it and if the venous is higher than the arterial then the brain is sending it out.
Is the arteriovenous difference of a substance sufficient to determine the rate of consumption?
No, you have to take into account the blood flow and the oxygen.
Weight of brain? % of total energy consumption it accounts for? O2 consumption?
1.4kg, 2% of total mass, but it uses 25% of glucose, and 20% of O2
Is cerebral blood flow correlated to metabolism? To local brain functional activity?
Yes and yes, released NTs encourage increased blood flow
a. yes see equation. If there is blood flow then oxygen can be consumed, but brain also will use aerobic glycolysis when pyruvate is produced in excess of that needed for oxidative phsophorylation.
b. When there is neuronal activity it releases glutamate and there is no reuptake of Glu by the presynaptic neuron instead it goes to astrocyte end feet and that activates a pathway to produce arachidonic acid and that can produce things like prostaglandins and constrict or dialate arterioles and change blood flow. So when there is metabolism going on in the neuron then blood flow can be increased.
What substrates can replace glucose? Under what circumstances does this occur?
Lactate and pyruvate can replace glucose in times of hypoglycemia, or when there is an abundance of lactate
a. Ketone bodies (beta hydroxybutyrate and acetoacetate)
b. Occurs in neonates (suckling), in adults who are fasting, ketogenic diet (no carbs), or hibernation.
c. Requires 28% less O2 to make the same amount of ATP
How is metabolism altered under pathological states such as hypoxia, ischemia, hypoglycemia, hyperammonemia, depression, zombification, etc.?
a. Hypoxia: CMR-G is increased to try and get more ATP-glycolysis. CMR-O2 will go down b/c there is no oxygen in blood.
b. Ischemia: CMR-G will increase to try and get more ATP-glycolysis. CMR-O2 will stay same or go down depending how much restriction of blood flow there is.
c. Hypoglycemia: brain needs glucose but there isn’t any for it to use so CMR-G will decrease and CMR-O2 will stay the same?? Brain will use ketone bodies for energy
d. CO poisoning: hemoglobin is tied up with CO and not oxygen. CMRO2 will decrease. CMR-G will increase b/c glycolysis will be increased
e. Drowning: blood flow is not there. CMRO2 will go down. CMR-G will increase
f. Heavily sedated: blood flow is normal. Cells aren’t activated or firing and they don’t need as much ATP. CMRG and CRMO2 go down.
g. Seizure: all neurons firing a lot. CRMG and CRMO2 increase
What is the energy budget of the brain?
25% of all glucose consumption and 20% of all oxygen consumption
What is the lactate shuttle?
Glucose is taken up by the astrocyte from the blood and it is converted to pyruvate and then lactate which is transported to the neuron where it is converted to pyruvate and used to make energy.
What are the roles of astrocytes in brain metabolism?
a. Take up glutamate and convert to glutamine and shuttle back to neuron to turn in to glutamate.
b. Undergo glycolysis and produce ATP and shuttle lactate to neuron where it can then be used for oxidative phosphorylation.
c. Take up glutamate and convert to arachidonic acid and constrict or dilate blood vessels to increase or decrease glucose uptake.
