1.6 BCHM - Brain Neuronal Metabolism Flashcards
What is the primary source of fuel for the brain?
Glucose.
Is brain metabolism almost exclusively aerobic or anaerobic? And why?
Aerobic.
The brain burns 20% of the body’s ATP = 10x more energy than average tissue. It has no time for the meager production of ATP that anaerobic metabolism produces, that would take too long and be too slow. It needs a lot of energy fast.
What is all this glucose being metabolized in the brain used for?
80% of the ATP hydrolized in the brain powers formation and maintenence of ionic gradients.
Recal: These ionic gradients (ex: Na/K+) use ACTIVE transport and therefore burn ATP.
What is the name of the glucose transporter channels on the liver, muscle, fat, and brain cells?
Liver - Glut2
Muscle / Adipose - Glut4
Brain - Glut1/Glut3
What type of transport do the transporter channels on liver, muscle, adipose, and brain use in order to get glucose into the cell? How do they keep glucose in the cell?
They use FACILITATED DIFFUSION.
Glucose cannot get through the membrane, therefore they must supply this channel.
No energy is used in this transport.
Each of these cells has HEXOKINASE and phosphorylates glucose as soon as it enters the cell in order to trap it and use it.
Associate each glucose transporter with its corresponding Km value? Explain what Km value means?
Glut1/ Glut3 - 20.
Glut4 - 90.
Glut 2 - 300.
Km value of an enzyme indicates the concentration of substrate which is sufficient for the rate of catalysis to be half of the maximum rate of catalysis.
Correlate Km value with affinity for substrate. Using this, explain why each tissue type has its associated Km value.
High Km = low substrate affinity.
Low Km = high substrate affinity.
Brain - always needs glucose, low Km indicates that even when glucose is in low concentration, the brain is getting its share.
Muscle/ Adipose - in constant action, need glucose, but not as severely as the brain.
Liver - is altruistic, it will continue taking in glucose even when glucose levels are high in the blood, it will also let that glucose out into the blood when blood levels are low so the other tissue types can get their share.
Observe the graph below. The pink line is representative of Glut4 transporters, green line is representative of Glut2 transporters, and blue line is Glut1/3 transporters. What would happen in all three after a large (glucose filled) meal, what about during starvation? Answer in terms of speed of glucose import into the cell.
After a meal glucose import would increase. However, notice that glucose import flatlines in Glut1/3 at a relatively low blood glucose level. Whereas in Glut4 transporters they continue importing glucose for a long period even at high blood glucose levels.
At starvation glucose import would decrease. However notice that in Glut1/3 cells they are still scraping in glucose for quite sometime, even at very low blood glucose levels.
Glut1 and Glut3 are which type of CNS glucose transporters (blood-brain endothelial cells or neuronal cell membranes)? I know he said to not worry about this but its easy enough and it makes sense for the next few cards.
Glut1 - blood-brain barrier endothelial cells (glucose passes through these 1st).
Glut3 - neuronal cell membranes.
What are astrocytes when referring to neurons? What is their role in glucose metabolism? (What is the transfer of glucose between astrocytes and neurons? Why is this important?).
Astrocytes are the workhorse cells of the brain, play many roles to suport neurons.
Astrocytes absorb glucose directly through BBB.
Astrocytes make glycogen as an energy buffer for neurons, in case there is a glucose shortage and the brain needs energy.
Due to astrocytes lacking Glucose-6-phosphatase they cannot release glucose straight over to neurons. So they break it down into lactate and transfer it to neurons. This provides the majority of energy to the neurons because of their ability to use the Citric Acid Cycle.
What type of metabolism do astrocytes vs. neurons use?
They can both use aerobic metabolism.
However, astrocytes can use anaerobic and then pass the glucose (in the form of lactate) over to the neuron to finish.
Since glucose is the main energy source for the brain, it dies if we get too hypoglycemic right? Can it use any other fuel source in dyer situations?
It can in severe cases.
But! it usually switches its fuel supply to ketone bodies.
The liver produces three ketone bodies. Of the three in the picture below, which can be catabolized by the brain to supplement glucose in generating energy? Identify the ketone functional group in each, which one isn’t a ketone but can act in a manner similar?
Acetoacetate and B-hydroxybutarate.
Acetone is already broken down pretty far and supplys no energy.
If there is a diabetic patient that comes to your office and is presenting in a bit of a altered state, what is one physical finding that could let you know they are most likely hypoglycemic and in need of some sugar?
Due to the lack of glucose in their body they will have begun catabolizing ketones, this gives off a fruity essence in their breath and is a sign that they are hypoglycemic.
The body holds a sufficient amount of fat that can be burned as fuel for most cells. However, the brain does not contain these types of cells. How is this gap bridged so that the brain can survive when there is little glucose and abundant fat supply?
Ketone bodies, as mentioned before, are an intermediate form of fuel that allows the brain to tap into this abundant reservoir of energy stored in the form of fat.
What are the major cell type (or organ) players in this ketone body production pathway? What is an intermediate in this pathway and what is the reason that intermediate cannot be passed directly to the brain?
Adipose tissue = releases fatty acids.
Liver = oxidizes fatty acid to produce acetyl CoA, then uses the thioester bond of acetyl-CoA to produce ketone bodies.
Brain = uses high energy carbon bonds of ketone bodies to regenerate high energy thioester bonds of acetyl-CoA.
Acetyl-CoA generated by the liver does not have the ability to be transferred directly to the brain due to its size and insolubility.
90% of the bodys fat is stored in what form? How is it converted from this form into the form released?
Stored as triacylglycerol.
Hydrolyzed into glycerol and free fatty acids which can be exported through membrane of fat cell.
