Brain Metabolism Flashcards
What are the major pathways for energy metabolism in the brain?
The major pathway in adults is glycolysis for the production of ATP. In neonates who are breast feeding (breast milk 50% fat), their main energy source is from ketone bodies from the beta oxidation of fats.
What is the role of brain glycogen?
There is very little glycogen in the brain relative to the muscles and liver. It serves as an emergency source that can provide ATP for 4-6 minutes in the absence of blood glucose.
What are the key regulatory sites in brain glucose metabolism?
Hexokinase, PFK, and pyruvate kinase.
For each mole of glucose consumed by the brain, how much is converted to lactate under aerobic conditions? Under anaerobic (stroke) conditions?
Under aerobic conditions, 1/6 of the mole of glucose gets converted to lactate. Under anaerobic conditions, all of the glucose gets converted to lactate.
Are there alternative pathways of glucose metabolism?
Ketone body metabolism.
How is brain metabolism of any substrate measured?
Measure what goes in and what comes out.
Cerebral Metabolic Rate = (Arter. Conc- Venous Conc.)(BloodFlow)/Weight
Is the arteriovenous difference of a substance sufficient to determine the rate of consumption?
No, you need blood flow and weight.
Is cerebral blood flow correlated to metabolism? To local brain functional activity?
More blood flow into a region causes dramatic increase in glucose use, but not oxygen use. This is because the astrocytes are making lactate.
What substrates can replace glucose? Under what circumstances does this occur?
Ketone bodies (D-3-Hydroxybutyrate and Acetoacetate). Under fasting conditions, fat and protein diet (ketogenic), or when breast feeding (mothers milk is 50% fat).
How is metabolism altered under pathological states such as hypoxia, ischemia, hypoglycemia, hyperammonemia, depression, etc.?
See slide 11.
What is the energy budget of the brain?
?
What is the lactate shuttle?
Astrocytes pick up glucose from the blood through the GLUT1, convert to pyruvate through glycolysis, than to lactate with lactate dehydrogenase. The lactate then gets shipped to the neuron, which makes it back into pyruvate, then into ATP.
What are the roles of astrocytes in brain metabolism?
Many roles. Astrocytic end-feet are attached to the neuron while it’s processes are attached to the synapse. Through the release of glutamate in the neural synapse, phospholipase A2 is activated in the astrocyte. This makes AA, which in the presence of lactic acid i.e. brain is active and in need of oxygen, will become Prostaglandin E2, a vasodilator. Otherwise 20-HETE vasocontricts.
Also, pull glutamate from synapse and return it to the neuron as glutamine, which is synaptically inert.
Also, shuttles lactate produced from blood glucose into the neuron, providing energy for the neuron.
