How does the brain couple cerebral blood flow with metabolism/energy need?
through the neurovascular unit
the astrocyte senses the activity goign on in the nearby neuron, so it signals to the capillary through its end feet to vasodilate and bring more blood to the area
Which utilize more ATP? Glia or neurons?
neurons - about 75%
What is the breakdown of what neurons use energy for?
44% synaptic transmission
15% resting potential
16% action potential
Besides using the glucose for energy or glycogen synthesis, what is about 2.5% of the glucose used for in adults?
enters the pentose phosphate shunt to form NADPH for nucleotide biosynthesis - or any anabolic process basically
THe glycogen held in reserve for the brain would only last about ____ during hypoxia.
would only maintain ATP levels for about 4-6 minutes
What is the biochemical basis for Wrnicke-Korsakoff syndrome?
it's a vitamin B1 deficiency
this vitamin is a cofactor for the transketolase and transaldolase enzymes for the pentose phosphate pathway
without it, you don't get NADPH synthesis and thus no nucleotide biosynthesis
What are the two important regulatory steps of glycolysis?
phosphofructokinase and pyruvate kinase
What are the main regulatory steps of the TCA cycle?
pyruvate dehydrogenase (inhibited by ATP and NADH)
How can you measure the rate at which the brain is using something like glucose?
calculate the cerebral metabolic rate:
CMR = (arterial concentration in - venous concentraiton out) x flow / weight
Why is the CMR - O2 typically higher than the CMR - G?
Because oxidation of glucose for energy requires 6 molecules of O2
If you need 6 molecules of O2 to oxidize one molecule of glucose, why is the CMR-O2 not six times higher than the CMR-G?
because some of the glucose is processed anaerobically to lactate
What will happen to the CMR-G and CMR-O2 during a stroke when there isn't enough blood flow to the brain?
the CMR-G will increase because the neurons will frantically try to speed up glycolysis to keep ATP high
CMR O2 can't get any higher because there's no blood flow, so it will either stay the same or drop off
What will happen to the CMR-O and CMR-G in carbon monoxide poisoning?
the brain essentially becomes hyposic, so same as stroke
CMR-G will increase to ramp up glycolysis for ATP
CMRO2 goes down (remember that glycolysis doesn't require O2)
What happens to the CMR-G and CMR-O in someone who's drowning?
CMRO2 goes down, CMRG goes up
What will happen to the CMR-G and CMR-O in someone who's heavily sedated and unconscios?
Both CMRG and CMRO will go down because the brain isn't active
What will happen to the CMRG and CMRO in someone with epilepsy duringa seizure?
CMRG and CMRO2 will both shoot up because the neurons are firing like crazy and need ATP
Through what biochemical pathway does the astrocyte signal the blood vessel to vasodilate?
Some of the Glutamate that is released into the synapse will be taken up by the astrocye. It will act on reeptors that increase PLA2 activity and arachidonic acid production
AA can be transformed to prostaglandins to either dilate or constrict the blood vessels thoruh endfeet.
DUring neuronal activity (the very start of it), blood flow increases, glucose use increases, oxygen availability increases, but osygen USE does not change. Why is this?
Because the first few steps are the astrocytes using the glucose to signal the capillary to vasodilate and this is an anerobic process - technically "aerobic glycolysis"
we don't know why they do this
In what cells is the glycogen stored?
If pyruvate is produced in excess of what is needed for oxidative phosphorylation, what is it converted into?
What happens tot he lactate that the astrocytes make from the glucose? WHat is this called?
it's transported into the neurons through the MCT2 transorters and it's processed back into pyruvate for the TCA within the neuron
this is the astrocyte-neuron lactate shuttle
What else can the brain use for fuel besides glucose? When?
ketone bodies - acetoacetate and D-3-Hydroxybutyrate
- in neonates on mom's milk
- in aduls who are fasting, starving, or on a ketogenic diet
- in animals that are hivernating
How does ketone utilization compare to glucose in terms of O2 expenditures? How might this be clinically important for stroke?
it uses 28% less O2 for an equivalent ATP synthesis - if we could spark ketone use in someone who's had a stroke, we may give them a little more time