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MSK Week 3 > 2.3.4. Glycolysis IV > Flashcards

2.3.4. Glycolysis IV Flashcards

1
Q

What is our baseline blood glucose level?

A

5 mM

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2
Q

What is Km?

A

Substrate concentration at which you reach half Vmax

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3
Q

What is one of the main roles of the liver?

A

Maintains blood glucose levels (the brain uses glucose as its primary food source)

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4
Q

Glucokinase

A

Present in the liver (catalyzes the first step in the uptake of glucose)

Specific for glucose

High Km

No product inhibition

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5
Q

Hexokinase

A

All tissues (catalyzes first step in the uptake of glucose)

Non-specific for hexokinase

Low Km

Product inhibition (G6P binds to an allosteric site, shutting hexokinase down)

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6
Q

What is the purpose of feedback inhibition of hexokinase?

A

It prevents G6P over-accumulation in peripheral tissues (this reduces the pool of inorganic phosphate in the cell)

This is bad because it stops the production of ATP and cells die (this is why all the phosphorylated intermediates are normally kept at low concentration within all cells)

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7
Q

What is glucokinase not inhibited?

A

Allows the liver to take up glucose without limit when blood glucose is high

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8
Q

How does the liver deal with too much G6P

A

Can convert it to glycogen for storage or to pyruvate (for its own energy or can convert it to fat)

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9
Q

What activates PFK-1?

A

F26BP (liver) and AMP (muscle)

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10
Q

What inhibits PFK-1?

A

ATP, Citrate, and H+

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11
Q

What causes F26BP to rise?

A

Insulin (indicating that the body is going through the “fed state”) causes phosphatases (PP-1) to be stimulated causing PFK2 to be dephosphorylated

F26BP accumulates and PFK1 is more active

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12
Q

What is glycogen?

A

The storage form of carbohydrates

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13
Q

Specifically, how does F26BP get formed?

A

After a meal, F26BP is formed from F6P by phosphofructokinase 2 (PFK2)

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14
Q

What happens to F26BP in the fasting state?

A

Glucagon is elevated, PFK2 is phosphorylated by protein kinase A (which is activated by cAMP)

Phosphorylated PFK2 converts F26BP to F6P and PFK1 is less active

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15
Q

What does high levels of citrate indicate?

A

That adequate amounts of substrate are entering the TCA cycle, and that intra-mitochondrial levels of NADH and ATP are high (therefore, glycolysis shuts down via PFK1 inhibition)

TCA cycle cannot keep pace with glycolysis

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16
Q

What is AMP a good indicator of?

A

Its concentration jumps of 20 fold when the body is undergoing exercise (activates PFK1)

17
Q

What are the major regulatory enzymes in skeletal muscle?

A

Hexokinase and PFK1

18
Q

What are the major regulatory enzymes in the liver?

A

Glucokinase, PFK1 (activated by F26BP), and pyruvate kinase

19
Q

What activates pyruvate kinase?

A

F16BP

20
Q

What inactivates pyruvate kinase?

A

ATP

21
Q

Why is PFK2 bipolar?

A

It acts as a kinase in the fed state and a phosphatase during fasting

22
Q

protein kinase A

A

Phosphorylates PFK2, leading to more F6P and less active PFK1

Activated by cAMP

23
Q

phosphatase

A

De-phosphorylates PFK2, leading to more F26BP and more active PFK1

Activated by insulin

24
Q

High proton levels in the cytosol are indicative of what?

A

Glycolysis is going too fast, so the anaerobic pathway is relied on

This leads to overproduction of lactate and H+

H+ inhibits PFK1

25
Q

What happens when you are oxygen deprived?

A

Oxidative phosphorylation does not work as fast at it should (ATP is not generated as fast as it should be)

Energy charge of the cell drops, and anaerobic pathway is accelerated (glucose to lactate)

26
Q

What is the first committed step in glycolysis?

A

Step 3: F6P to F16BP via PFK1

Step 1 is an irreversible step, but G6P has several fates (i.e., not committed to glycolysis)

27
Q

What must be recycled in order to continue with glycolysis?

A

NAD+ and Pi

28
Q

What is the adenylate kinase reaction?

A

2 ADP → ATP + AMP

Generates another usable ATP from 2 ADP

29
Q

What reaction occurs to make ADP from ATP and AMP from ADP

A

Irreversible hydrolysis

30
Q

F6P + ATP →

A

F16BP + ADP

31
Q

How do tumors contribute to lactic acidosis?

A

Tumors have extremely active glycolysis (i.e., lots of lactic acid)

Lactic acids helps the tumor spread through tissue by acting as a signaling molecule

32
Q

Where does cyanide exert its inhibitory effect?

A

Cytochrome oxidase (ETC)

Leads to lactic acidosis

33
Q

How does CO lead to lactic acidosis

A

Binds irreversible to hemoglobin with a greater affinity than oxygen

34
Q

Definition of fermentation

A

An ATP-generating process in which organic compounds act as both donors and acceptors of electrons

Usually occurs anaerobically (uses NAD+ in an upstream step and re-generates NAD+ in a downstream step)

35
Q

Lactobacillus

A

An example of fermentation

Glucose + 2ADP + 2Pi →
2 lactate + 2 ATP

36
Q

Yeast

A

Glucose + 2ADP + 2Pi →

2 Ethanol + 2CO2 + 2 ATP

MSK Week 3 (8 decks)

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