Hexose Monophosphate Pathway Flashcards

1
Q

The hexes monophosphate pathway(HMP) is also called …

A
  • pentose phosphate pathway
  • hexose monophosphate shunt
  • 6-phosphogluconate pathway
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2
Q

What 3 pentose phosphates are generated by the HMP?

A
  • Ribose 5-phosphate. (Required for synthesis of RNA and DNA)
  • Ribulose 5-phosphate
  • Xylulose 5-phosphate
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3
Q

Where are the HMP enzymes located?

A

In the cytosol of of all cells

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4
Q

HMP is an alternate route for the …

A

Oxidation of glucose

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5
Q

When glucose is used for storage, what does it become?

A

Glycogen, starch, sucrose

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6
Q

What does glucose become when oxidized by the pentose phosphate pathway?

A

Ribose 5-phosphate

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7
Q

What are the key functions of the HMP pathway?

A
  • generation of NADPH
  • Generation of pentose, e.g. ribose 5-phosphate for nucleotide biosynthesis
  • Interconversions of dietary carbohydrates into glycolysis/gluconeogenesis intermediates
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8
Q

What are the primary tissues of of HMP?

A
  1. Liver, Adipose tissue, lactating mammary glands
  2. adrenal cortex, ovaries, Testes, placenta
  3. Erythrocytes
  4. White blood cells and macrophages
  5. Thyroid
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9
Q

Discuss the Liver, Adipose tissue, lactating mammary glands as primary tissues of HMP

A

Liver, Adipose tissue, lactating mammary glands- NADPH provided for fatty acid biosynthesis

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10
Q

Discuss adrenal cortex, ovaries, Testes, placenta as primary tissues of HMP

A

adrenal cortex, ovaries, Testes, placenta- NADPH provided for synthesis of steroid hormones- hydroxylation reactions

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11
Q

Discuss erythrocytes as a primary tissue of HMP

A

Erythrocytes- NADPH provided for the reduction of glutathione as a protection against oxidative damage

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12
Q

Discuss White blood cells and macrophages as primary tissues of HMP

A

White blood cells and macrophages- NAPDH provided for killing phagocytosed bacteria

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13
Q

Discuss the thyroid as a primary tissue of HMP

A

Thyroid -NADPH as a coenzyme for the synthesis of thyroid hormone

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14
Q

What are phases of HMP?

A
  • Oxidative phase

- Nom-oxidative phase

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15
Q

Explain the characteristics of the oxidative phase

A
  • reactions are irreversible
  • forms NADPH and pentose phosphate, ribulose-5-P
  • Enzymes are dehydrogenases
  • Reaction Catalyzed by G-6PDH is the major regulatory site for the entire HMP
  • Glucose 6-phosphate + 2NADP+ + H2O —> ribulose 5-phosphate + CO2 + 2NADPH + 2H+
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16
Q

Give the characteristics of non-oxidative phase of HMP

A
  • reactions are reversible
  • Results in the formation of ribose 5-p for nucleic acid biosynthesis
  • interconversion of sugars resulting in the formation of glycolytic intermediates- feed to glycolysis/gluconeogenesis
  • Enzymes are trans ketolase and transaldolase
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17
Q

Describe the events of the 1st step oxidative phase of the HMP pathway

A

Glucose 6-phosphate converted to 6-phosphogluconate

Enzymes involved: glucose 6-phosphate dehydrogenase and 6-phosphogluconolactone hydrolase

-reduction of H2O + NADP+ —> NADPH + H+

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18
Q

Describe the 2nd step of the oxidative phase of the HMP phase

A

6-phosphogluconate is converted to ribulose 5-phosphate + CO2

Enzyme involved: 6-phosphogluconate dehydrogenase

Decarboxylation yields CO2

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19
Q

What are the products of the oxidative phase of the HMP pathway?

A
  • Reduction of NADP+ —> NADPH + H+ (2)
  • A decarboxylation, yielding CO2
  • The product is ribulose-5-P
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20
Q

What are the regulators of G6P DH?

A
  • Allosterically stimulated by NADP+
  • Inhibited by NADPH

-Activated by insulin- up regulation:
Increase of amount of enzyme

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21
Q

What is the rate limiting(committed ) step of the oxidative step of the HMP pathway?

A

Glucose 6-phosphate(6C) converted to 6-phosphogluconolactone

Enzyme: glucose 6-phosphate dehydrogenase

NADP+ —> NADPH

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22
Q

Walkthrough the enzymes involved in the oxidative phase of HMP

A
  1. Rate limiting step :Glucose 6-phosphate- (6C) converted to 6-phosphogluconolactone

Enzyme: glucose 6-phosphate dehydrogenase

NADP+ —> NADPH

  1. 6-phosphogluconolactone(6C) —> 6-phosphogluconate(6C)

Addition of water

Enzyme: lactonase

  1. 6-phosphogluconate (6C) —>ribulose 5-phosphate(5C)

Enzyme: 6-phosphogluconate
Produces CO2
- NADP+—>. NADPH

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23
Q

What is the function of lactonase?

A

6-phosphogluconolactone(6C) —> 6-phosphogluconate(6C)

Addition of water

Enzyme: lactonase

  • The lactonase intermediate is unstable
  • Lactonase catalyzes ring opening
  • It acts as a hydrolase- H2O
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24
Q

What is the function of 6-phosphogluconate dehydrogenase?

A

6-phosphogluconate (6C) —>ribulose 5-phosphate(5C)

Enzyme: 6-phosphogluconate
Produces CO2
- NADP+—>. NADPH

  • Catalyzes a 2nd oxidative reaction
  • An unstable B-keto acid intermediate
  • NADP+ and Mg2+ are required
  • Decarboxylation —> a keto pentose I.e. ribulose-5-P
25
What are the products of the Non-oxidative phase
Glyceraldehyde 3-P And Fructose 6-P
26
Which phase of the HMP is the link to glycolysis/gluconeogenesis?
Non-oxidative phase
27
What is the non-oxidative phase of HMP pathway?
A pool of pentose-P interconversions
28
What is the 1st step of the Non-oxidative phase /4 the step of the HMP pathway?
Ribulose 5-phosphate converts to ribose 5-phosphate Enzyme: ribose 5 phosphate isomerase 2 carbons are transferred in transketolase
29
What is special about tissues which use NADPH than ribose 5-phosphate?
In tissues requiring primarily NADPH rather than ribose 5-phosphate, the pentose phosphates can be recycled into glucose 6-phosphate
30
What is reductive biosynthesis?
reactions in fatty acid synthesis and synthesis of steroid hormones
31
What is cytochrome P450?
A coenzyme for reductive biosynthesis
32
What are the coenzymes of NADPH?
Cytochrome P450 Glutathione reductase NADPH oxidase
33
What is glutathione reductase?
A coenzyme of reductive biosynthesis- to reduce oxidative stress via reduction of H2O2
34
What is NADPH oxidase?
A coenzyme of reductive biosynthesis-immunity via phagocytosis of pathogens by WBCs
35
What processes produce NADPH?
- Irreversible oxidative phase of the HMP pathway | - NADP+ dependent malate dehydrogenase (except for erythrocytes)
36
What processes consume NADPH?
- fatty acid synthesis - steroid synthesis - drug metabolism - glutathione reduction - Generation of super-oxide in phagocytes by NADPH oxidase
37
What can result from the NADPH oxidase mutations?
Mutations in gene for NADPH oxidase lead to decrease enzymatic activity This causes chronic granulomatous disease
38
What is nitric oxide synthesis?
Generation of nitric oxide and reactive oxygen species by phagocytosis
39
How does NADPH prevent oxidative stress?
It reduces glutathione via glutathione reductase Which converts reactive H2O2 into H2O via glutathione peroxidase If absent, the H2O2 would be converted to hydroxyl free radicals which can attack the cell
40
Describe the formation reactive oxygen species
Reduction of molecular oxygen in a series of one-electron steps yields superoxide, hydrogen peroxide, hydroxyl radical, and water The intermediate, activated forms of oxygen are known as reactive oxygen species (ROS)
41
Give the reactions required to form ROS intermediates
Oxygen +e- —> superoxide (oxygen molecule radical) Superoxide + e- —> H2O2 H2O2 + e- —> hydroxyl radical OH-⏺ Hydroxyl radical + e- —> H2O
42
What is the effect of reactive oxygen species on cells?
Environmental insults causes cellular damage Damage to lipids, proteins, nucleic acids, and carbohydrates This leads to cell damage and cell death
43
Describe glutathione (GSH) as an antioxidant enzyme
Reduced glutathione (GSH) protects the cell by destroying hydrogen peroxide and hydroxyl free radicals Regeneration of GSH from its oxidized form (GS-SG) requires the NADPH produced in the glucose 6-phosphate dehydrogenase reaction
44
Give some examples of antioxidants scavengers(clearing of ROS)
Vitamin C-ascorbic acid Vitamin E- tocopherols Vitamin A- Carotenoids
45
What is the function of Cytochrome P-450 Monooxygenase systems in the mitochondrial system ?
Important in the synthesis of steroid hormones from cholesterol
46
What is the function of Cytochrome P-450 Monooxygenase systems in the microsomal system ?
Important in detoxification of toxins, pesticides, organic compounds, drugs
47
Give the reaction of Cytochrome P-450 monooxygenase systems
Substrate R may be steroid, drug, or other chemical + O2 + NADPH + H+( NADPH acts as a reducing equivalent) Cytochrome. P 450 Products: ROH(hydroxyl group created + H2O + NADP+
48
How does NADPH yelp immunity?
- Phagocytosis of pathogens - Leukocytes, macrophages, neutrophils utilize oxygen-dependent mechanisms to destroy bacteria (oxidative burst) - Requires the generation of superoxide as well as other reactive oxygen species - NADPH oxidase in parts responsible for this production
49
What happens during NADPH oxidase deficiency ?
Deficiency of NADPH oxidase causes chronic granulomatous disease characterized by severe persistent infections
50
Explain the pathway during phagocytosis to explain NADPH importance to immunity
1. Attachment of pathogen to a phagocytocytic cell 2. Ingestion of organism 3. Destruction of the microorganisms 4. NADPH + O2 —> O2-(RADICAL) + NADP+ (catalyzed by NADPH oxidase/ this is the respiratory burst 5. O2- (radical) either spontaneously or superoxide dismutase, is converted to hydrogen peroxide 6. Myelo peroxidase absorbs Cl- to create OCl- or converts hydrogen peroxide to OH(radical) be converting Fe3+ to Fe2+ 7. OCl- and OH(radical) together make hypochlorite acid which destroy bacteria
51
Infections result in....
Increased production of oxidants
52
Where is nitric oxide synthesized?
-Synthesized in endothelial cells (vascular endothelial cells and lymphatic endothelial cells), and neural tissue
53
What are the coenzymes of NO synthase?
- Flavin mononucleotide (FMN) - Flavin adenine dinucleotide (FAD) - heme - tetrahydrobiopterin
54
Give the reaction of NO synthesis
L-Arginine + O2 + NADPH + H+—> NADP+ +NO + L-citrulline Enzyme: NO synthase
55
How does NO help with relaxation of smooth muscle?
Synthesized NO diffuses into vascular smooth muscle and activates cytosolic guanylate cyclase to form cyclic guanosine monophosphate (cGMP), eventually resulting in smooth muscle relaxation
56
How do vasodilators like nitroglycerin and nitroprusside cause smooth muscle relaxation
Vasodilators such as nitroglycerin and nitroprusside are metabolized to NO resulting in smooth muscle relaxation and lowering of blood pressure. NO is considered an endogenous vasodilator
57
What are the functions of Nitric oxide (NO)?
- relaxes smooth muscle - prevents platelet aggregation - prevents platelet aggregation - neurotransmitter in the brain - mediates tumoricidal and bacterial actions of macrophages
58
How can NO help with macrophages?
Activated macrophages form oxygen free radicals that combine with NO to form compounds more bactericidal than NO itself