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What is the primary source of fuel for the brain?
Glucose
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Why is brain metabolism mostly aerobic?
Brain uses 20% of the body’s ATP so must generate a lot of ATP
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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)
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How does glucose get into the brain?
Facilitated diffusion via GLUT transporters
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An enzyme with a high Km has a __________________ affinity for substrate
Low
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An enzyme with a low Km has a __________________ affinity for substrate
High
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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
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GLUT2 is located in ____________________ and has a Km value of _____________
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GLUT4 is located in ___________________ and has a Km value of _____________
- Adipose tissue and muscle
- 90 mg/dl
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GLUT1 is located in ___________________ and has a Km value of _____________
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GLUT3 is located in ___________________ and has a Km value of _____________
- Neurons
- 10 mg/dl in neurons
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What is the blood brain barrier?
Endothelial cells that cover the entire capillary system of the brain that restricts what can enter the brain
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Glucose must pass through ___________ transporter before it can pass through _____________ transporter
- GLUT1 (BBB)
- GLUT3 (neurons)
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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
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What is the role of astrocytes in the brain?
Absorb glucose directly through the BBB to make glycogen
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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
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When needed, _____________________ in astrocytes hydrolyze glycogen to glucose-6-phsophate
Glycogen phosphorylase
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Why must astrocytes use lactate as fuel instead of glucose?
Only liver and kidney cells have glucose-6-phosphatase
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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
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__________________ is normally the sole source of fuel for the brain, but during starvation the brain can supplement its fuel supply by using ____________________
Ketone bodies
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The liver produces which ketone bodies? Which of these can the brain catabolize?
Acetone, acetoacetate, D-β-hydroxybutarate
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Why is D-β-hydroxybutarate different than acetone and acetoacetate?
D-β-hydroxybutarate does not have a ketone
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Energy from ketone bodies is stored as ____________________
Fat
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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
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90% of fat in the body is stored in the form of ____________________
Triacylglycerols
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Triacylglycerols are hydrolyzed into ______________ and ________________ which can be exported through the membrane of the fat cell
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β-oxidation of fatty acids in hepatocytes produces _____________________, which in turn will be used to produce ketone bodies
Acetyl-coenzyme A
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The liver uses _________________ to form carbon-carbon bonds of ketone bodies
Thioester bonds
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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
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What is the function of HMG-CoA reductase?
Reduces 3-hydroxy-3-methyl glutaryl CoA into mevalonate
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What is the function of HMG-CoA lyase?
Lyses 3-hydroxy-3methyl glutaryl CoA leading to ketone body synthesis
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