Brain uses 20% of the body’s ATP so must generate a lot of ATP
What does the brain do with all the energy it uses?
80% of ATP used by brain powers formation and maintenance of ionic gradients (Na+/K+ pump)
How does glucose get into the brain?
Facilitated diffusion via GLUT transporters
An enzyme with a high Km has a __________________ affinity for substrate
Low
An enzyme with a low Km has a __________________ affinity for substrate
High
What does Km indicate?
The concentration of substrate which is enough for the rate of catalysis to be half of the maximum rate of catalysis
GLUT2 is located in ____________________ and has a Km value of _____________
Liver
300 mg/dl
GLUT4 is located in ___________________ and has a Km value of _____________
Adipose tissue and muscle
90 mg/dl
GLUT1 is located in ___________________ and has a Km value of _____________
BBB
20 mg/dl
GLUT3 is located in ___________________ and has a Km value of _____________
Neurons
10 mg/dl in neurons
What is the blood brain barrier?
Endothelial cells that cover the entire capillary system of the brain that restricts what can enter the brain
Glucose must pass through ___________ transporter before it can pass through _____________ transporter
GLUT1 (BBB)
GLUT3 (neurons)
Which can transport glucose faster, BBB or neurons? Why?
Neurons, because they have a lower Km than BBB
GLUT1 Km = 20 mg/dl
GLUT3 Km = 10 mg/dl
What is the role of astrocytes in the brain?
Absorb glucose directly through the BBB to make glycogen
What is the process of astrocytes feeding neurons?
1. Take glucose through BBB
2. Turn glucose into glycogen
3. Glycogen converted to glucose when needed
4. Glucose turned into lactate
5. Lactate fed to neurons
When needed, _____________________ in astrocytes hydrolyze glycogen to glucose-6-phsophate
Glycogen phosphorylase
Why must astrocytes use lactate as fuel instead of glucose?
Only liver and kidney cells have glucose-6-phosphatase
How do astrocytes and neurons work in conjunction during metabolism?
Astrocytes do anaerobic metabolism to create lactate and send the lactate to the neuron
Neurons do aerobic metabolism using the lactate
__________________ is normally the sole source of fuel for the brain, but during starvation the brain can supplement its fuel supply by using ____________________
Ketone bodies
The liver produces which ketone bodies? Which of these can the brain catabolize?
Acetone, acetoacetate, D-β-hydroxybutarate
Why is D-β-hydroxybutarate different than acetone and acetoacetate?
D-β-hydroxybutarate does not have a ketone
Energy from ketone bodies is stored as ____________________
Fat
Can the brain use fat as fuel?
Brain can’t burn fat or convert fat to glucose, but you can get two-carbon skeletons from fat and then make ketone bodies
90% of fat in the body is stored in the form of ____________________
Triacylglycerols
Triacylglycerols are hydrolyzed into ______________ and ________________ which can be exported through the membrane of the fat cell
Glycerol
Free fatty acids
β-oxidation of fatty acids in hepatocytes produces _____________________, which in turn will be used to produce ketone bodies
Acetyl-coenzyme A
The liver uses _________________ to form carbon-carbon bonds of ketone bodies
Thioester bonds
Explain why fasting leads to a buildup of ketone bodies
When you fast you start burning fat and that creates ketone bodies
What is 3-hydroxy-3-methyl glutaryl CoA?
A precursor used to make ketone bodies or cholesterol
What is the function of HMG-CoA reductase?
Reduces 3-hydroxy-3-methyl glutaryl CoA into mevalonate
What is the function of HMG-CoA lyase?
Lyses 3-hydroxy-3methyl glutaryl CoA leading to ketone body synthesis