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Biochemistry > Pentose Phosphate Pathway > Flashcards

Pentose Phosphate Pathway Flashcards

1
Q

What is another name for the pentose phosphate pathway?

A

Hexose MonoPhosphate(HMP) shunt

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2
Q

A pentose phosphate pathway is a branch off the glycolytic pathway. It has two main purposes. What are they?

A
  • Generation of NADPH

* Generation of the 5-carbon sugar ribose, to be used in the synthesis of nucleotides

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3
Q

The pentose phosphate pathway can produce both ____ and _____, or it can produce only ____ or only _____, depending on the needs of the cell. 

A

ribose and NADPH

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4
Q

No ____ is produced or used during the pentose phosphate pathway.

A

ATP

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5
Q

What are the oxidative irreversible reactions of the pentose phosphate pathway?

A

Step 1: Dehydrogenation of Glucose 6-P.
Step 2: Hydrolysis to 6phosphogluconate.
Step 3: Oxidative decarboxylation of 6-phosphogluconate.

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6
Q

What is the rate limiting step of PPP?

A

Step 1: Dehydrogenation of Glucose 6-P.

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7
Q

What is the enzyme for the dehydrogenation of glucose 6-P?

A

Glucose 6-phosphate dehydrogenase (G6PD)

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8
Q

The dehydrogenation of glucose 6-P is a major point of regulation of the PPP. ______ is a required coenzyme and ______ is potent competitive inhibitor.

A
  1. NADP+

2. NADPH

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9
Q

Expression of dehydrogenation of glucose 6-P is upregulated by _____.

A

Insulin

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10
Q

During PPP’s dehydrogenation of glucose 6-P, the flux _____.

A

It increases in absorptive state.

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11
Q

What is the enzyme for step 2 of the PPP (hydrolysis to 6-phosphogluconate)?

A

6-phosphogluconolactone hydrolase

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12
Q

What are characteristics of the hydrolysis to 6-phosphogluconate?

A
  • Irreversible
  • NOT rate limiting
  • Produces 1 NADP
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13
Q

The third step of PPP is the _______.

A

oxidative decarboxylation of 6-phosphogluconate. • It is irreversible and it produces 1 NADPH.

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14
Q

What is the enzyme for the oxidative decarboxylation of 6-phosphogluconate?

A

6-phosphogluconate dehydrogenase

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15
Q

The Nonoxidative Reversible Reactions of the PPP are steps:

A

Steps 4-8: Interconversions of sugar molecules.

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16
Q

Interconversions of sugar molecules in steps 4-8 interconvert sugars with ___ to ___ C-atoms.

A

3 to 7

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17
Q

The interconversions of sugar molecule steps permit synthesis of ____ used for nucleotide production.

A

ribose 5-P

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18
Q

What is the enzyme for steps 4-8?

A

Transketolase

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19
Q

Transketolase requires ____.

A
  • requires TPP (from thiamine)
  • important in diagnosing thiamine deficiency
  • Done by measurement of its activity in RBCs
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20
Q

What are the functions of NADPH?

A
  1. Electron donor for the “reductive” biosynthesis of fatty acids, cholesterol and steroids.
  2. Electron donor for the neutralization of ROS -reactive oxygen species (H2O2, superoxide etc.).
  3. Provides reducing equivalents for Cytochrome P450 Monooxygenase system (for a biosynthesis of steroids, and detoxification of xenobiotics).
  4. Play role in phagocytosis (destruction of pathogens by macrophages and neutrophils).
  5. Substrate for the synthesis of nitric oxide (NO).
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21
Q

NADPH is an ____ for the “reductive” biosynthesis of fatty acids, cholesterol and steroids.

A

electron donor

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22
Q

NADPH is an electron donor for the ______ of ROS-reactive oxygen species (H2O2, superoxide etc.).

A

neutralization

23
Q

NADPH provides reducing equivalents for ______________ system (for a biosynthesis of steroids, and detoxification of xenobiotics).

A

Cytochrome P450 Monooxygenase

24
Q

NADPH plays a role in _______ (destruction of pathogens by macrophages and neutrophils).

A

phagocytosis

25
Q

NADPH is a substrate for the synthesis of _______.

A

nitric oxide (NO)

26
Q

When and how are ROS produced?

A

Reactive Oxygen Species produced:
• during aerobic metabolism
• through reactions with drugs and toxins
• when levels of antioxidants are diminished

27
Q

What are used to neutralize ROS?

A

Tripeptide: gamma-Glutamylcysteinglycine: G-SH  Glutathion(GSH/GSSG) is the major antioxidant system

28
Q

What is Monooxygenase?

A

It’s an enzyme that will incorporate 1 O atom from molecular oxygen (creating a –OH group) with the other being reduced to H2O

29
Q

What are the two systems of Cytochrome P450 monooxygenase (CytP450)?

A
  1. Mitochondrial system–for synthesis of steroids.

2. Microsomal system –for detoxification of foreign. compound

30
Q

Mitochondrial Cytochrome P450 is associated with what type of mitochondrial membrane?

A

inner

31
Q

In steroidogenic tissues (placenta, ovaries, testes and adrenal cortex), Mitochondrial Cytochrome P450 uses _____ for synthesis of steroid hormones

A

NADPH

32
Q

In liver Mitochondrial Cytochrome P450 uses the same system to synthesize ____ and ____.

A

bile acids and vitamin D3

33
Q

In kidney Mitochondrial Cytochrome P450 converts vitamin D3 to its _____.

A

active form

34
Q

Microsomal system Cytochrome P450 is associated with the membranes of the ______ in liver cells

A

smooth ER

35
Q

Microsomal system Cytochrome P450 ______ drugs, toxins and other chemicals

A

detoxifies

36
Q

With Microsomal system Cytochrome P450 , by adding ________ the compound may be inactivated (or for some drugs, activated), made more soluble, or provide a reactive group ______ for attachment of other compound

A

oxygen (hydroxyl groups)

hydroxyl

37
Q

NADPH plays a role in phagocytosis. It happens in white blood cells in ______ and _____.

A

neutrophils and macrophages (monocytes)

38
Q

NADPH generates _______ that aid in killing the microorganisms that they have engulfed.

A

oxygen free radicals

39
Q

______ is a combination of NADPH oxidase and myeloperoxidase are used to generate the oxygen free radicals to aid in the destruction of microorganisms.

A

The MPO system

40
Q

Chronic Granulomatous Disease (CGS) is a

A

Rare genetic NADPH oxidase deficiency.

  • persistent severe infections due to the inability to kill bacteria forming granulomas
  • The granuloma is formed as a defense where the body attempts to “wall off” the collection of cells from the rest of the body
41
Q

NADPH Role in nitric oxide (NO) Synthesis. NO is synthesized from ____, _____, and _____.

A

arginine, oxygen and NADPH

42
Q

What are properties of NO?

A

Properties of NO –very short half life (seconds), very reactive (reacts with oxygen), since it is a gas, it diffuses into cells very easily.

43
Q

What is nitric oxide’s enzyme?

A

NO-synthase (NOS)

44
Q

NO-synthase (NOS)–3 enzymes product of different genes:

A
  • nNOS–neural tissues
  • eNOS–endothelial cells
  • iNOS-inducible

Constitutively expressed at constant levels.

45
Q

What is the biological activity of NO?

A
  1. Smooth muscle relaxant (this is the basis for nitroglycerin action which is converted into NO to relax vascular smooth muscle) 
  2. Used by macrophages to generate free radicals to assist in killing microorganisms 
  3. Inhibits platelet aggregation 
  4. Functions as a neurotransmitter in brain
46
Q

Glucose 6-Phosphate Dehydrogenase (G6PD) Deficiency has the inability to detoxify _________.

A

oxidizing agents

47
Q

The gene for G6PD is on the _______.

A

X chromosome (seen mostly in males).

48
Q

In whom and where is G6PD deficiency more common?

A

Worldwide, it is one of the most common single gene disorders(estimated 400 million affected).
• In some areas 25% of males are affected.
• The populations with the highest incidence are among those of African, Mediterranean, or Asian descent

49
Q

With G6PD deficiency, as with sickle-cell and the ______, there is some protection against malaria that accounts for the high gene frequency. (The incidence is about 11% among American Blacks.)

A

thalassemia

50
Q

G6PH deficiency is usually only symptomatic when experiencing an oxidative stress. Name examples.

A
  • infection(oxygen radicals generated by macrophages)
  • drugs that produce an oxidative stress
  • fava beans (some variants of G6PD deficiency, but not all)…this is also called Favism)
51
Q

What are clinical manifestations of G6PH deficiency ?

A
  • Almost exclusively in RBCs as an episodic hemolytic anemia in adults
  • Neonatal jaundice in newborns (increased production of unconjugated bilirubin).
  • The effects on other organs/tissues are due to the hemolytic anemia.
  • Shortened lifespan in individuals with the severe form.
52
Q

G6PD happens almost exclusively in RBCs as an episodic ________ in adults.

A

hemolytic anemia

53
Q

Why does G6PD deficiency happen almost exclusively in RBCs?

A
  • Because in RBCs, the only pathway to make NADPH (to neutralize free radicals) is via HMP pathway.
  • In other cells types other pathways contribute to NADPH formation.
  • More importantly, since RBC do not have a nucleus, they can NOT synthesize more G6PD to replace any enzyme that is lost.
  • Most of the mutations that result in G6PD deficiency affect the stability of the enzyme, which means over the life cycle of a red blood cell (~110 days) the enzyme is lost and not replaced.
54
Q

G6PD deficiency impairs the ability of an erythrocyte to form ______ resulting in hemolysis.

A

NADPH

Biochemistry (2 decks)

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