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Biochem Exam 3 > 27 - Pentose Phosphate Pathway > Flashcards

27 - Pentose Phosphate Pathway Flashcards

1
Q

What are 3 other names for the pentose phosphate pathway?

A

Hexose Monophosphate Pathway
Pentose Shunt
Phosphogluconate Pathway

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2
Q

The oxidative phase of the pentose pathway makes what?

A

NADPH

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3
Q

The oxidative phase consists of 3 reactions. The first is the oxidation of glucose 6-phosphate to form a lactone using the enzyme…

A

Glucose 6-Phosphate dehydrogenase

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4
Q

What is the rate-limiting step of the pentose pathway?

A

Glucose 6-Phosphate dehydrogenase

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5
Q

The oxidative phase consists of 3 reactions. The second is the use of a hydrolase called _________ (opens the ring by adding water) to convert 6-Phosphoglucono-delta-lactone into 6-Phosphogluconate.

A

Lactonase

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6
Q

The oxidative phase consists of 3 reactions. The third is the oxidative decarboxylation of 6-Phosphogluconate to form Ribulose-5-phosphate using the enzyme…

A

6-Phosphogluconate dehydrogenase

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7
Q

In the oxidative phase, which reactions reduce NADP+ to NADPH?

A 
Reaction 1 (G6P dehydrogenase) 
Reaction 3 (6-Phosphogluconate dehydrogenase)
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8
Q

We need NADPH for ________ and ________.

A

Anabolism

Reduction

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9
Q

NADPH is needed for the synthesis of monomers, such as…

A

Fatty acid biosynthesis
Cholesterol biosynthesis
Neurotransmitter biosynthesis
Nucleotide biosynthesis

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10
Q

NADPH is also need as a reducing power, especially in the maintenance of reduced _________ (red blood cells).

A

Glutathione

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11
Q

Glutathione is a tripeptide made up of what 3 amino acids?

A

Glutamate – Cysteine – Glycine

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12
Q

Glutathione can interact with proteins without an ________.

A

Enzyme

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13
Q

In glutathione, _______ bonds stabilize the protein structure but only at the proper locations (cysteine).

A

Disulfide

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14
Q

Reactive oxygen species (generated in oxidative metabolism) help maintain the redox homeostasis of cells but overall they are bad because they cause damage to _________ and can lead to cell death.

A

Macromolecules

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15
Q

Reduced glutathione is important in dealing with ROS because it is used along with ________ ________ to eliminate peroxides (ROS).

A

Glutathione peroxidase

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16
Q

After GSH is used against ROS, it is back in its oxidized form GSSG. This is when ________ is used along with glutathione reductase to convert is back to its reduced form, GSH.

A

NADPH

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17
Q

What would happen without NADPH?

A

GSSG could not be reduced to GSH, and GSH would not be available to combat peroxides (ROS) so they would continue to damage the cells and cause oxidative stress.

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18
Q

In healthy cells with plenty of NADPH, the ratio of GSH:GSSG is maintained at…

A

500:1

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19
Q

This is a disease that causes a deficiency in NADPH production.

A

Glucose 6-Phosphate Dehydrogenase Deficiency (G6PDD)

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20
Q

This disease is the most common genetic disease. About 400 million people have it worldwide and it has a 7.5 percent allele frequency.

A

Glucose 6-Phosphate Dehydrogenase Deficiency (G6PDD)

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21
Q

G6PDD is ____-linked ________ disease with about 200 reported missense mutations.

A

X-linked recessive

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22
Q

This class of G6PDD has less than 10 percent activity of Glucose 6-Phosphate Dehydrogenase and has the symptom of chronic hemolytic anemia.

A

Class I

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23
Q

This class of G6PDD has less than 10 percent activity of Glucose 6-Phosphate Dehydrogenase and has the symptom of acute hemolysis due to normal levels of oxidant stress.

A

Class II

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24
Q

This class of G6PDD has 10-60 percent activity of Glucose 6-Phosphate Dehydrogenase and has the symptom of acute hemolysis due to high levels of oxidant stress.

A

Class III

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25
Q

This class of G6PDD has 60-90 percent activity of Glucose 6-Phosphate dehydrogenase and has normal function.

A

Class IV

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26
Q

This class of G6PDD has greater than 150 percent activity of Glucose 6-Phosphate dehydrogenase and has normal function.

A

Class V

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27
Q

What are the 3 types of erythrocyte diseases that can occur due to G6PDD?

A

1) Hemoglobinopathies
2) Membrane/Cytoskeleton defects
3) Metabolic errors

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28
Q

RBCS are destroyed in hours/weeks, not months. Mutant G6PD often has a shortened lifetime. Fe in heme must be (OXIDIZED/REDUCED) to bind O2. However, mutant G6PD can cause it to be (OXIDIZED/REDUCED) and precipitate which leads to the formation of Heinz bodies.

A

Reduced

Oxidized

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29
Q

T/F. Acute/Induced anemias are temporary.

A

True

30
Q

These are used to take out Heinz bodies. They look like a bite taken out of a cell.

A

Bite cells

31
Q

Other proteins can make NADPH when there is a deficiency due to G6PDD. Isocitrate dehydrogenase has 3 isozymes. 1 uses NAD+ in the TCA cycle, and 2 use NADP+. Of these two, one is in the ________ and one is in the ________. Which one can be used, why?

A

Mitochondria
Cytoplasm

The one in the cytoplasm can be used, but the one in the mitochondria can’t because RBCs don’t have mitochondria.

32
Q

Another way to get NADPH is through Malic Enzyme (ME1) interconverting malate and pyruvate in the cytoplasm. Why won’t this work in RBCs?

A

Malate comes from the TCA cycle, which occurs in mitochondria. RBCs do not have mitochondria.

33
Q

The most severe effect of G6PDD occurs in neonates and is due to the ________ being unable to conjugate ________. The blood however, is normal.

A

Liver

Bilirubin

34
Q

Excessive amounts of unconjugated bilirubin causes ________ (>5 mg/dL vs. 1.5-2 mg/dL).

A

Jaundice

35
Q

When ________ enters the brain (kernicterus), deafness, cerebral palsy, or death can result.

A

Bilirubin

36
Q

G6PD has 3 options for structure. This particular structure is inactive, consists of a 514 amino acid chain, and is good for conditions favoring increased NADPH, G6P, and pH.

A

Monomer

37
Q

G6PD has 3 options for structure. This particular structure is active, is composed of a homodimer, and is good for conditions of increased ionic strength and pH greater than 8.

A

Dimer

38
Q

G6PD has 3 options for structure. This particular structure is active, is composed of a dimer of dimers, and is good for conditions of increased NADP+ and decreased pH less than 6.

A

Tetramer

39
Q

_______ is both a substrate and a coenzyme.

A

NADP+

40
Q

This disease is an autosomal recessive mutation in ATM. It consists of a progressive loss of coordination starting in childhood and sensitivity to mutagens (like radiation).

A

Ataxia Telangiectasia

41
Q

The ______ protein is responsible for controlling rate of cell division. It imitates DNA damage repair response after DSBs. It consists of a Serine/Threonine kinase and activates HSP27 via p38 MAPK cascade.

A

ATM

42
Q

HSP27 is important because it interacts with _______ and promotes its dimerization, which is its active form.

A

G6PD

43
Q

T/F. Without ATM (such as in disease AT), HSP27 is not being activated, which leads to G6PD not being promoted to dimerize and become active.

A

True

44
Q

What are 3 ways for G6PD regulation?

A

1) Transcription/Translation control
2) Location in cell
3) Post-translational controls

45
Q

What are activators of G6PD?

A

1) Dimerization
2) Transcription factors for antioxidant genes
3) Cell cycle and synthesis activators
4) Insulin

46
Q

What are inhibitors of G6PD?

A

1) Phosphorylation (of G6PD itself)

2) Apoptosis-signaling proteins

47
Q

Insulin (ACTIVATES/INHIBITS) G6PD.

A

Activates

48
Q

T/F. Decreases in extracellular glucose can stimulate G6PD in some cell types but inhibit it in other cell types.

A

False. Increases in extracellular glucose can stimulate G6PD in some cell types but inhibit it in other cell types.

49
Q

Pancreatic ______ cells produce insulin. These cells are lost as a result of diabetes pathology.

A

Beta-islet

50
Q

Pancreatic Beta-islet cells naturally express (HIGH/LOW) levels of G6PD.

A

Low

51
Q

T/F. In pancreatic Beta-islet cells, high external glucose results in decreased G6PD.

A

True

52
Q

In pancreatic Beta-islet cells, they naturally express low levels of G6PD and high external glucose results in decreased G6PD. This explains why G6PDD patients are likely to develop _______.

A

Diabetes

53
Q

In the non oxidative phase, shuffle 1 consists of Ribulose 5-phosphate isomerization. What enzyme is used to form what tautomer?

A

Ribose 5-phosphate isomerase

Ribose 5-phosphate

54
Q

In the non oxidative phase, shuffle 1 consists of Ribulose 5-phosphate isomerization. What enzyme is used to form what epimer?

A

Ribulose 5-phosphate epimerase

Xylulose 5-phosphate

55
Q

In the non oxidative phase, shuffle 2 consists of using _________ to transfer 2-C from Xylulose 5-phosphate (5-C), leaving behind Glyceraldehyde 3-phosphate (3-C).

A

Transketolase

56
Q

In the non oxidative phase, shuffle 2 moves 2-C with transketolase. These 2-C are added to either Ribose 5-phosphate to make ____________ or Erythrose 4-phosphate to make ____________.

A

Sedoheptulose 7-phosphate

Fructose 6-phosphate

57
Q

In the non oxidative phase, shuffle 2 transition states are stabilized by what?

A

TPP coenzyme

58
Q

In the non oxidative phase, shuffle 3 transfers 3-C units with the use of ___________. They are transferred from Sedoheptulose 7-phosphate (7-C), leaving behind ___________ (makes Transketolase substrate).

A

Transaldolase

Erythrose 4-phosphate

59
Q

In the non oxidative phase, shuffle 3 transfers 3-C unit from Sedoheptulose 7-phosphate onto ___________ making ___________ (makes same product as Transketolase).

A

Glyceraldehyde 3-phosphate

Fructose 6-phosphate

60
Q

In the non oxidative phase, shuffle 3 transition states are stabilized by what?

A

Lys side chain

61
Q

In the non oxidative phase, shuffle 4 consists of the regeneration of ___________ for the use of gluconeogenesis.

A

Glucose 6-phosphate

62
Q

What is used in shuffle 4 for the gluconeogenesis pathway to help make glucose 6-phosphate?

A

GAP

F6P

63
Q

This mode is used when much more Ribose 5-phosphate than NADPH is required. For example, rapidly dividing cells need Ribose 5-phosphate for the synthesis of nucleotide precursors of DNA. The non oxidative phase occurs in reverse.

A

Mode 1

64
Q

What is the primary product of mode 1?

A

Ribose 5-phosphate

65
Q

This mode is used when the needs for NADPH and Ribose 5-phosphate are balanced. This occurs in normal, everyday function.

A

Mode 2

66
Q

What is the primary product of mode 2?

A

Ribose 5-phosphate

NADPH

67
Q

This mode uses all 4 shuffles and is used when much more NADPH than Ribose 5-phosphate is required. For example, adipose tissue requires a high level of NADPH for the synthesis of fatty acids.

A

Mode 3

68
Q

This mode uses 3 shuffles and is used when both NADPH and ATP are required. It’s important for more power. In this mode, ATP and NADPH are concomitantly generated, and five of the six carbons of G6P emerge in pyruvate.

A

Mode 4

69
Q

What is the primary product of mode 3?

A

NADPH

70
Q

What is the primary product of mode 4?

A

Fructose 6-phosphate

GAP

Biochem Exam 3 (10 decks)

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