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T1 - Phase 1 - Integrated (I) > Cardio - Biochemistry - Pentose Phosphate Pathway > Flashcards

Cardio - Biochemistry - Pentose Phosphate Pathway Flashcards

1
Q

True/False.

Glucose molecules that just entered the liver are likely to both be phosphorylated to glucose 6-phosphate and enter both glycolysis and the pentose phosphate shunt.

A

True.

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2
Q

Where does the pentose phosphate pathway take place?

What types of tissue needs are answered by increased pentose phosphate pathway activity?

A

In the cytosol;

NADPH needs (e.g. for fatty acid synthesis, cholesterol/steroid synthesis, glutathione reduction)

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3
Q

What substance is very important as a reducing agent in fatty acid/steroid/cholesterol synthesis?

Via what pathway is it produced?

A

NADPH;

the pentose phosphate pathway

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4
Q

What are the two phases of the pentose phosphate pathway?

A

Oxidative phase (irreversible)

Nonoxidative phase (reversible)

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5
Q

Describe the general reaction that occurs in the oxidative phase of the pentose phosphate pathway.

A

Glucose-6-phosphate is oxidized to:

  • 2 NADPH
  • Ribulose-5-phosphate
  • CO2

(irreversible)

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6
Q

Describe the general reaction that occurs in the nonoxidative phase of the pentose phosphate pathway.

A

Ribose-5-phosphate is converted to:

  • Nucleic acids
  • GAP (glyceraldehyde 3-phosphate)
  • F6P

(reversible)

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7
Q

What is the first enzyme of the oxidative phase of the pentose phosphate pathway?

This enzyme is especially important because it is the:

A

Glucose-6-phosphate dehydrogenase;

rate-determining enzyme

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8
Q

What pathway uses ribose-5-phosphate as a substrate?

A

Nucleotide biosynthesis (DNA synthesis)

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9
Q

NADPH is used as a reducing agent for which biosynthetic pathways?

A

Fatty acid synthesis

Steroid/cholesterol synthesis

Glutathione reduction

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10
Q

What is the main difference between NADPH and NADH in their function/use?

A

NADPH - used for biosynthesis

NADH - used for energy production

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11
Q

For each individual glucose molecule that enters the pentose phosphate pathway, how many NADPH are produced?

A

2 NADPH per G6P

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12
Q

The pentose phosphate pathway committed step is performed by which enzyme?

A

Glucose-6-phosphate dehydrogenase

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13
Q

Differentiate between the structure of ribulose-5-phosphate and ribose-5-phosphate sugars in the pentose phosphate pathway.

A

RibULOSE-5-phosphate = keto sugar

RibOSE-5-phosphate = aldose sugar

(Note: image is of trioses, not pentoses)

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14
Q

The isomerization of ribulose-5-phosphate to ribose-5-phosphate occurs as part of what reaction in the oxidative phase of the pentose phosphate pathway?

A

The 4th (and final) reaction

(beginning of nonoxidative steps)

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15
Q

Transketolase is the enzyme used in the 2nd step of the nonoxidative phase.

What cofactor is required by this enzyme?

A

Thiamine pyrophosphate

(derivative of vitamin B1)

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16
Q

What are the three enzymes of the nonoxidative phase of the pentose phosphate shunt?

A

Epimerase, transketolase, transaldolase

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17
Q

Describe the ‘shell game’ that the nonoxidative phase of the pentose phosphate shunt uses to move carbons around and get from ribose 5-phosphate to any of the following:

glyceraldehyde 3-phosphate, fructose 6-phosphate, glucose 6-phosphate

A
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18
Q

How does the nonoxidative phase of the pentose phosphate shunt get from a pentose (ribose 5-phosphate) back to trioses (glyceraldehyde 3-phosphate) and hexoses (fructose 6-phosphate, glucose 6-phosphate)?

A

2-carbon (taken from X5P) added to 5-carbon (R5P)

–> 7-carbon (S7P)

1-carbon taken from S7P (and added to 3-carbon (G3P) –> 4-carbon (E4P))

–> F6P

–> G6P

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19
Q

What three glycolytic intermediates can be made from the pentose phosphate shunt?

From which phase?

A

Glyceraldehyde 3-phosphate, fructose 6-phosphate, glucose 6-phosphate;

nonoxidative

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20
Q

The nonoxidative phase of the pentose phosphate pathway requires 3 enzymes for its four reactions

- epimerase, transketolase & transaldolase -

which one(s) require thiamine pyrophosphate as a cofactor?

A

Only transketolase

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21
Q

Discuss the role of the epimerase used in the nonoxidative phase of the pentose phosphate pathway.

A

It converts ribulose-5-phosphate to its epimer xylulose-5-phosphate

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22
Q

What two glycolytic intermediates are formed by the reactions of xylulose-5-phosphate (from the nonoxidative phase of the pentose phosphate pathway)?

A

Glyceraldehyde-3-phosphate;

fructose-6-phosphate

23
Q

As concentrations of NADPH increase in the cell, how will this regulate enzymatic function?

A

Strongly inhibits glucose-6-phosphate dehydrogenase

(initial enzyme in PPP)

24
Q

What is the role of NADPH in red blood cells?

A

Reduce glutathione

–>

Protect membrane from oxidative damage (free radicals)

25
Q

True/False.

If a cell needs (1) only NADPH, or (2) only ribose 5-phosphate, or (3) both, it can tailor the pentose phosphate shunt to meet its needs.

A

True.

Only NADPH - Ribulose 5-P turned back into G6P (goes back into oxidative phase)

Both - Ribulose 5P turned into ribose 5-P

Only ribose 5-phosphate - Oxidative portion shut down; nonoxidative runs in reverse (F6P and GAP –> R5P)

26
Q

Describe how a cell can modify the pentose phosphate shunt for each of the following conditions of need:

(1) only NADPH
(2) only ribose 5-phosphate
(3) both

A

Only NADPH - Ribulose 5-P turned back into G6P (goes back into oxidative phase)

Only ribose 5-phosphate - Oxidative portion shut down; nonoxidative runs in reverse (F6P and GAP –> R5P)

Both - Ribulose 5P turned into ribose 5-P

27
Q

How would a red blood cell regulate the two phases of the pentose phosphate pathway?

Will it produce NADPH, ribose 5-phosphate, or both?

A

RBC has no nucleus (and so no DNA synthesis) — oxidative phase will be uninhibited to produce only NADPH

(the nonoxidative phase will take ribulose-5-phosphate and convert it to glucose-6-phosphate so it can reenter the oxidative phase)

28
Q

How would a cell that requires a lot of nucleotide synthesis and no NADPH regulate the pentose phosphate pathway?

A

Only the nonoxidative portion matters, but in reverse –> F6P and GAP are converted to R5P

(Oxidative phase will be shut down to prevent ANY NADPH production (which would inhibit glucose-6-phosphate dehydrogenase and prevent ribose-5-phosphate production).)

29
Q

If the oxidative phase of the pentose phosphate pathway is effectively shut down, what would a cell use to create a steady stream of ribose-5-phosphate?

A

Glycolytic intermediates:

glyceraldehyde-3-phosphate and fructose-6-phosphate

30
Q

How much energy can be made from NADPH in oxidative phosphorylation?

A

None; it is only a biosynthetic reducing agent.

(It is not like NADH.)

31
Q

What is the major controlling factor for the pentose phosphate pathway?

What other factor plays an important role?

A

NADPH concentrations;

xylulose 5-phosphate levels

32
Q

Discuss the effect of rising xylulose-5-phosphate levels in the cell following a large meal.

(Note: Xylulose 5 -phosphate is produced in the pentose phosphate pathway.)

A

Xylulose-5-phosphate activates phosphoprotein phosphatase (PP2A);

fed state –> dephosphorylates PFK-2/FBPase-2 enzyme –> increases glycolysis / decreases gluconeogenesis

33
Q

What is the importance of creating xylulose-5-phosphate from ribulose-5-phosphate?

A

Xylulose-5-phosphate is a regulatory molecule for carbohydrate and lipid metabolism.

*X5P structure is also used to form glycolytic intermediates

34
Q

What is the role of phosphoprotein phosphatase (PP2A)?

A

Dephosphorylates PFK-2/FBPase-2 enzyme

–>

Increases glycolysis / decreases gluconeogenesis

35
Q

When the PFK-2/FBPase-2 enzyme is dephosphorylated, what results?

A

PFK-2 is activated

FBPase-2 is inhibited

(increases glycolysis / decreases gluconeogenesis)

36
Q

When PFK-2 is activated by the regulatory activity of xylulose-5-phosphate, what are the downstream effects?

A

PFK-2 increases fructose-2,6-bisphosphate levels,

activating glycolysis and inhibiting gluconeogenesis

37
Q

When xylulose-5-phosphate levels rise and induce their regulatory actions on phosphoprotein phosphatase and the PFK-2/FBPase-2 enzyme, what is the end result of this regulatory pathway?

A

Increased fructose-2,6-bisphosphate levels –> increased levels of acetyl-CoA (through glycolysis)

38
Q

If high levels of glucose-6-phosphate leads to increased NADPH, and high levels of ribose-5-phosphate (also X5P) lead to increased acetyl-CoA, what metabolic process will ultimately follow?

A

NADPH and Acetyl-CoA both increase fatty acid synthesis

39
Q

How does the tripeptide (3 amino acids) glutathione help protect the cell membrane from reactive oxygen species (ROS)?

A

Glutathione is an antioxidant (the SH group is easily oxidizable);

also, it and glutathione peroxidase decrease H2O2 levels

40
Q

What three amino acids make up a glutathione molecule?

A

Glutamine - cysteine (SH side chain here) - glycine

41
Q

Reduced glutathione (90%) is:

Oxidized glutathione (10%) is:

A

Glutathione-SH

Glutathione disulfide (glutathione-S—S-glutathione)

42
Q

How many molecules of glutathione are needed to reduce H2O2 to H2O? What redox state do the glutathione molecule(s) need to be in?

A

2;

reduced state (GSH, not GS-SG)

43
Q

What enzyme reduces glutathione (GSSG to 2 GSH)?

What enzyme oxidizes glutathione (2 GSH to GSSG) and decreases intracellular hydrogen peroxide?

A

Glutathione reductase;

glutathione peroxidase

44
Q

How does NADPH help with glutathione peroxidase-mediated protection against H2O2?

A

NADPH provides the reducing power for glutathione reductase

45
Q

What is the role of glutathione reductase?

A

Take an oxidized glutathione dimer (GSSG) and tranforms it into two molecules of reduced glutathione (GSH)

46
Q

What is the most common enzyme disorder?

A

Glucose-6-phosphate dehydrogenase (G6PD) deficiency

47
Q

Quinine (an antimalarial drug) is oxidative and causes an increase in reactive oxygen species (ROS), sometimes leading to a decrease in a patient’s RBC count.

How does quinine do this?

A

Hemolytic anemia (especially in individuals with G6PD deficiency)

  • Decreased NADPH —>*
  • Glutathione can’t be reduced –>*
  • Membrane damaged by ROS*
48
Q

An alcoholic man shows up to the ER in a hemolytic crisis.

What is the most likely underlying cause?

A

Thiamine deficiency

(affects production of NADPH by the pentose phosphate pathway)

49
Q

What are the steps of the respiratory (oxidative) burst (from O2 to hypochlorite)?

What cells perform this function to create reactive oxygen species?

A

NADPH + 2 O2 – (NADPH oxidase) –> NADP+ + O2-

2 O2- – (superoxide dismutase) –> H2O2

H2O2 – (myeloperoxidase) –> HOCl

monocytes, macrophages, neutrophils

50
Q

What three enzymes are part of the respiratory (oxidative) burst?

What NADPH-dependent enzyme helps limit its damaging effects?

A

NADPH oxidase, superoxide dismutase, myeloperoxidase;

glutathione peroxidase

51
Q

What NADPH-dependent enzyme decreases the amount of H2O2 in the cell?

A

Glutathione peroxidase

2 GSH –> GSSG

H2O2 –> 2 H2O

52
Q

True/False.

Oxidizing drugs can easily deplete reduced glutathione stores and increase the effects of oxidation damage on RBCs.

53
Q

What population is at-risk for favism?

What substances should they avoid? Why?

A

Individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency;

oxidizing drugs, fava beans;

loss of reduced glutathione –> hemolytic anemia

T1 - Phase 1 - Integrated (I) (28 decks)

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