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BMB 402 > Chapter 14 Carb Metabolism and Gluconeogenesis > Flashcards

Chapter 14 Carb Metabolism and Gluconeogenesis Flashcards

1
Q

What are the main things accomplished by the pentose phosphate pathway?

A
  • reduces 2 NADP+ to NADPH
  • produces ribose-5-phosphate from glucose-6-phosphate

Overall:
- provides reducing power in the form of NADPH (which provides capacity for synthesis of molecules)
- generates ribose sugars
- can feed into glycolysis if ATP is needed

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2
Q

Where does the pentose phosphate pathway occur?

A

cytoplasm

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3
Q

What are the two phases of the pentose phosphate pathway?

A

oxidative and nonoxidative

In the oxidative phase, glucose-6-P is converted into ribulose-6-P, and 2 NADPH are produced to provide reducing power in other biosynthetic pathways. In the nonoxidative phase, ribulose-6-P is converted into glyceraldehyde-6-P and fructose-6-P.

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4
Q

What are the three metabolic states of the pentose phosphate pathway?

A
  1. if NADPH is required (glucose-6-P to be converted to ribose-5-P which makes NADPH)
  2. if nucleotide pools need to be replenished (use ribose-5-P to make more)
  3. if ATP levels are low (glucose-6-P to glycolysis)
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5
Q

What enzymes are the most important in the pentose phosphate pathway?

A

Glucose-6-phosphate dehydrogenase, transketolase (transfer of C2 units between sugars), and transaldolase (transfer of C3 units between sugars).

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6
Q

What is the committed step in the pentose phosphate pathway and how is it regulated?

A

The first step of the pathway, where glucose-6-P is converted to 6-phosphogluconolactone via G6PD is the committed step because this transformation is irreversible and has a large -∆G. High levels of NADPH inhibit this step through a negative feedback loop.

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7
Q

What does NADPH do?

A
  • is used in biosynthetic and detoxification pathways
  • used to reduce reactive oxygen species
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8
Q

What is the significance of ribose-5-phosphate?

A

It is the carb component of nucleotides and coenzymes

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9
Q

What is the net reaction of the pentose phosphate pathway?

A

6 Glucose-6-P + 12 NADP+ + 6 H2O —> 4 fructose-6-P + 2 G3P + 12 NADPH + 12 H+ + 6 CO2

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10
Q

What is glutathione?

A

Glutathione is a tripeptide that contains a free sulfhydryl group in its reduced form, which can donate electrons to reduce ROS and hydroxyl free radicals, preventing protein or lipid damage. For example, H2O2 is reduced to H2O, which is no longer harmful to the body.

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11
Q

What happens in the event of a glucose-6-phosphate dehydrogenase deficiency?

A
  • glutathione reserves are depleted
  • NADPH levels are lowered
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12
Q

What does gluconeogenesis accomplish?

A

Produces glucose from non-carbohydrate compounds

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13
Q

When does gluconeogenesis occur?

A

when dietary sources of glucose are low

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14
Q

Where does gluconeogenesis occur?

A

in the cytoplasm

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15
Q

What is the net reaction of gluconeogenesis?

A

2 Pyruvate + 2NADH + 4ATP +2GTP + 6H20 —> Glucose + 2NAD+ + 2H+ + 4ADP + 2GDP + 6P

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16
Q

What are the four major sources for glucose synthesis?

A
  1. Glycerol from breakdown of triglycerides
  2. CO2 fixation in chloroplasts (carbon fixation)
  3. break down of amino acids
  4. conversion of lactate to pyruvate (from anaerobic respiration)
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17
Q

What reactions of glycolysis are “bypassed” in gluconeogenesis and why?

A

Steps 1, 3, and 10 in gluconeogenesis are bypassed because they are highly unfavorable steps in the process of making glucose.

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18
Q

What is the first bypass reaction(s)?

A

Pyruvate kinase in glycolysis is bypassed by pyruvate carboxylase and phosphoenolpyruvate carboykinase.

Pyruvate is converted to oxaloacetate by pyruvate carboxylase

Oxaloacetate is converted to phosphoenolpyruvate by phosphoenolpyruvate carboykinase

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19
Q

What is the second bypass reaction?

A

PFK-1 is bypassed by fructose-1,6-bisphosphatase-1

Fructose-1,6-BP is converted to fructose-6-P by fructose-1,6-bisphosphatase-1 (reverse of step 3 in glycolysis)

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20
Q

What is the third bypass reaction?

A

Hexokinase is bypassed by glucose-6-phosphatase

Glucose-6-P is converted to glucose by glucose-6-phosphatase (reverse of step 1)

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21
Q

What activates pyruvate carboxylase?

A

acetyl-CoA

22
Q

What inhibits pyruvate carboxylase?

A

ADP

23
Q

Why is biotin important to pyruvate carboxylase?

A

It is a coenzyme needed for pyruvate carboxylase to work. It serves as a coenzyme for 5 total carboxylases.

Biotin is covalently linked to the epsilon amino group on lysine in the active site

24
Q

How is NADH needed for the one of the early steps of gluconeogenesis moved from the mitochondria to the cytoplasm?

A

NADH equivalent is transported by malate, which regenerates NADH in the cytoplasm

25
Q

What does the Cori Cycle do?

A

It converts lactate to glucose in the liver

The Cori Cycle does not require malate transport because it is converted to pyruvate before entering the mitochondria

In skeletal muscle, glycogen is converted to glucose, and is metabolized for energy (producing pyruvate). Under anaerobic conditions, pyruvate is converted to lactate, which can travel through the blood and be converted back to pyruvate in the liver via lactate dehydrogenase. This pyruvate is used in gluconeogenesis, and the resulting glucose travels through the blood back to muscle.

26
Q

What does the glucose produced in the liver do?

A

It replenishes glycogen stores in muscle

27
Q

What do fructose-2,6-BP and AMP activate? What do they inhibit?

A

activates PFK-1 (in glycolysis)
inhibits FBPase-1 (in gluconeogenesis)

28
Q

Where does gluconeogenesis primarily occur?

A

in the liver and kidneys

29
Q

Why is glucose-6-phosphate segregated in the ER lumen during gluconeogenesis?

A

For glucose to exit the cell, glucose-6-P must have its phosphate removed by glucose-6-phosphatase. However, if this is done in the cytoplasm, the glucose can be phosphorylated again by hexokinase and cannot leave the cell

30
Q

Why is fructose-2,6-BP so important?

A

It is a key regulator that helps maintain balance between glycolysis and gluconeogenesis.

31
Q

What does glucagon do?

A

Responds to low blood sugar by promoting glucose release and stimulating gluconeogenesis

32
Q

What does insulin do?

A

Responds to high blood sugar levels and promotes glucose storage; inhibits gluconeogenesis

33
Q

What is PFK-2/FBPase-2?

A

a key enzyme with both kinase and phosphatase activity

34
Q

When the kinase side is active, what does PFK-2/FBPase-2 do?

A

It phosphorylates fructose-6-P to fructose-2,6-BP to promote glycolysis flux (glycolysis is MORE active)

35
Q

What activates the kinase side of PFK-2/FBPase-2?

A

removal of the phosphate from serine by protein phosphatase 1

36
Q

When the phosphatase side is active, what does PFK-2/FBPase-2 do?

A

It removes the phosphate from fructose-2,6-BP to promote gluconeogenesis

37
Q

What activates the phosphatase side of PFK-2/FBPase-2?

A

phosphorylation of the serine residue by protein kinase A

38
Q

Where does glycogen degradation and synthesis occur?

A

in the cytoplasm

39
Q

What key enzymes regulate glycogen degradation and synthesis?

A
  • glycogen phosphorylase
  • glycogen synthase
  • glycogen branching and debranching enzyme
40
Q

True or false: glycogen degradation/synthesis is reversible

A

True

41
Q

What is the function of glycogen phosphorylase?

A

promotes release of glucose from the glycogen polymer; it is the enzyme that initiates glycogen degradation

42
Q

What is the function of glycogen synthase?

A

builds glycogen by making its chains longer

43
Q

What promotes the activity of glycogen synthase?

A

insulin

44
Q

Describe the structure and components of glycogen

A
  • has glycogenin protein
  • 50,000 glucose molecules with alpha 1,6 branches creating nonreducing ends
45
Q

What is the primary source of glucose for ATP production during muscle contraction?

A

glycogen degradation

46
Q

How does glycogen phosphorylase break down glycogen?

A

cleaves alpha 1,4 glycosidic bonds at nonreducing ends until it reaches within 4 glucose units of a branch point

47
Q

What regulates glycogen phosphorylase?

A

phosphorylation (often by phosphorylase kinase)

phosphorylated = active R state
dephosphorylated = inactive T state

48
Q

How does glycogen debranching enzyme work?

A
  • recognizes partially degraded branch
  • transfers 3 glucose units to nearest nonreducing end
  • cleaves alpha 1,6 glycosidic bond to release free glucose
49
Q

The synthesis of what molecule is required for glycogen synthase?

A

uridine diphosphate glucose (UDP glucose)

50
Q

How does glycogen branching enzyme work?

A

transfers 7 glucose residues from one end of the glycogen chain to a nearby chain

51
Q

What is glycogenin and what does it do?

A

It is a protein found in glycogen

It serves as an anchor protein for the glycogen core particle

Catalyzes the glycosyltransferase and synthesis reactions needed to generate glycogen

extends chain to 7 glucose residues

52
Q

What hormones activate and deactivate glycogen synthase?

A

epinephrine and glucagon deactivate glycogen synthase by inducing its phosphorylation by kinases (T state)

insulin activates glycogen synthase by inducing removal of the phosphate groups from it by a phosphatase (R state)

BMB 402 (14 decks)

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