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M2C Unit 2 Abali > Unit 2 - Abali - Lecture 8 - Hexose monophosphate pathway > Flashcards

Unit 2 - Abali - Lecture 8 - Hexose monophosphate pathway Flashcards

1
Q

Define pentose phosphate pathway

A

Metabolizes glucose to form ribose 5 phosphate and NADPH

Does not generate ATP

Does not require mitochondria. It takes place in the cytosol, which means that it takes place EVERYWHERE!!!

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2
Q

5 HMP intermediate enzymes

A

Glucose 6 phosphate dehydrogenase

6 phosphogluconate dehydrogenase

lactonase

Transketolocase

B1

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3
Q

Ribose 5 Phosphate

A

Crucial for nucleotide formation for DNA and RNA

It is a reversible reaction

High activity of PPP in tumor cells

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4
Q

Main functions of NADPH

A
  1. Reduction of biosynthesis
  2. Reduction of hydrogen peroxide (ROS)
  3. Phagocytosis by white blood cells
  4. Synthesis of nitric oxide
  5. Cytochrome P450 monooxygenase system
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5
Q

2 phases of HMP

A

Glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase

These 2 enzymes are dependent on NADP+-

NADP+ is converted to NADPH for the mechanism to work, so NADPH is just as important!

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6
Q

Oxidative phase

A

Removes hydrogen from glucose 6 phosphatase and gives it to NADP+

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7
Q

Non oxidative reversible phase

A

This process starts when the end product of the oxidative phase, R5P, comes into contact with isomerases and epimerases. These enzymes move the preexisting carbonic structure into different positions

This produces ribose 5 phosphate (different from ribulose), which is what is used for DNA and RNA

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8
Q

Crucial enzymes and coenzymes in the non oxidative reversible phase for HMP

A

Transketolocase and transaldolase

Coenzyme: thiamine pyrophosphate

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9
Q

Importance of thiamine pyrophosphate

A

Thiamine pyrophosphate is needed as a coenzyme to ensure transketolocase is working

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10
Q

Transketolocase

A

Starts the transfer of carbons that produce sedoheptulose-7-phosphate and glyceraldehyde-3-phosphate in one arm and the production of F6P and Glyceraldehyde 3 phosphate in the other arm

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11
Q

Transaldolase

A

This enzyme also pushes the transfer of carbons from fructose 6 phosphate and erythrose 4 phosphate

Catalyze the transfer of 2 and 3 carbon fragments

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12
Q

Ribulose-5-Phosphate Processing by Transketolase and Transaldolase: Explain the goals for each

A

Goal: form fructose 6 phosphate and glyceraldehyde 3 phosphate

To do this, ribulose 5 phosphate 3 epimerase converts ribulose 5 phosphate to xylulose 5 phosphate.

Goal 2: Ribulose 5 phosphate keto isomerase produces ribose 5 phosphate.

This also forms fructose 6 phosphate and glyceraldehyde 3 phosphate

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13
Q

Role of NADPH in cholesterol synthesis

A

NADPH is what makes cholesterol

Without cholesterol, we will not have corticosteroids, sex hormones, bile acids for the liver or vitamin D

We also will not be able to detoxify certain medications or harmful substances

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14
Q

Why is cholesterol synthesis crucial for smooth ER?

A

Smooth ER is in charge of packing lipids and exporting them

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15
Q

Is NADPH itself what is producing cholesterol?

A

NADPH itself isnt what is producing cholesterol. There is a completely separate mechanism for it. However, that mechanism would not work if NADPH did not donate hydrogen atoms to the mechanism

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16
Q

Role of NADPH in the Cytochrome P450 Monooxygenase System

A

This is a family of enzymes that contain heme

Oxygen reacts with a substrate to produce water, and it adds a hydroxyl group to the substrate

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17
Q

NADPH in mitochondria

A

Found in IMM (inner mitochondrial membrane)

Speeds up function of different cellular intermediates

Synthesizes steroid from cholesterol in the placenta, testes/ovaries, adrenal glands), bile acid synthesis in the liver, and activation of vitamin D (in kidney)

18
Q

NADPH in microsomes

A

Located in the membrane of the Smooth ER

Found mainly in liver hepatocytes

19
Q

How does NADPH help the liver excrete yucky stuff?

What other things does it do in the liver?

A

Add a hydroxyl group to label them nontoxic
Or add a hydroxyl group to make them more soluble so they can be peed or pooped out

It helps produce bile acid

It helps produce biologically active Vitamin D3

20
Q

Why does the HMP shunt transfer carbons?

A

to interconvert sugar phosphates

21
Q

I have C5 and C5. I want to use transketolocase. How many carbons will transfer?

A

2

C3 + C7

22
Q

I have C4 and C5. I want to use transaldolase. How many carbons are transferred?

A

2

C6 + C3

23
Q

I have C3 and C7. I want to use transaldolase. How many carbons are transferred?

A

3

C6 + C4

24
Q

Difference between NADPH and NADH?

A
25
Q

How Does NADPH Handle Oxidative Stress?

A

This is where oxidative stress is good, because it can kill of microbes

Superoxides kill viruses

Enzyme involved in converting oxygen into superoxides is NADPH OXIDASE, which has NADPH as its cofactor

It acts as a reducing agent to convert oxygen to superoxide

Superoxide then gets broken down to hydrogen peroxide and hypochlorite

These molecules are called reactive oxygen species

26
Q

Short term vs long term regulation of the HMP pathway

A

Short Term
Glucose 6-phosphate dehydrogenase (G6PDH) is the regulatory enzyme.
NADPH is a potent competitive inhibitor of the enzyme.

Long Term
Insulin activates transcription of glucose 6-phosphate dehydrogenase.

27
Q

RESPIRATORY BURST

A

Process where neutrophils use superoxides to kill microbes

28
Q

How Does NADPH Protect Against Oxidative Stress?

A

NADPH is crucial to erythrocytes (RBCs), because they are in charge of carrying and distributing oxygen

Glutathione Peroxidase, Glutathione 6 - Phosphate Dehydrogenase and glutathione reductase are all enzymes activated by NADPH. Their sole purpose is to get rid of ROS

29
Q

How can oxidative stress happen in erythrocytes?:

A

A superoxide radical can form if an accidental transfer of electrons from ferrous iron in heme takes place

If a superoxide radical forms, then methemoglobin is formed, and fe3+ does not bind to oxygen

This causes tissue hypoxia

We use glutathione peroxidase to fight back against this

29
Q

Glutathione Peroxidase

A

Glutathione peroxidase takes the ROS and turns it into water

30
Q

Reduced glutathione gives off how many electrons?

A

2

31
Q

What do these electrons do?

A

One electron is used to convert hydrogen peroxide into hydroxyl radicals

The other converts hydroxyl radical to H2O

32
Q

is it true that glutathione becomes oxidized after hydrogen peroxide is turned into water? Doesnt this mean that its counterproductive? Explain why or why not

A

Yes. Glutathione does become oxidized. This may seem counterproductive, but Glutathione REDUCTASE, takes this oxidized glutathione and reduces it, which also requires NADPH AS A COFACTOR!

Now glutathione is reduced and non ROS again!

33
Q

Oxidized glutathione is good, T or F?

A

FALSE!

34
Q

Glutathione 6 - Phosphate Dehydrogenase: Why is it so important? (Think full circle)

A

Without this enzyme, NADPH and ribose 5 phosphate would not form!

Without this enzyme, we would never be able to reduce oxidative stress!

35
Q

Cellular need: NADPH only. Fatty acid synthesis and detox. What is the fate of the pathway?

A

Oxidative reactions produce NADPH;

nonoxidative reactions convert ribulose 5P to glucose 6P to produce more NADPH.

36
Q

Cellular need: NAPDH and Ribose 5 P: Rapidly dividing cells. Fate of the pathway?

A

OX: produce NADPH and ribulose P

Isomerase converts ribulose to ribose 5P

37
Q

Cellular need: NADPH and pyruvate: Red Blood Cells

A

Both oxidative and nonoxidative reactions are used.

OX: generate NADPH and ribulose 5P.

Non OX: Convert ribulose 5P to fructose 6P and glyceraldehyde 3P.

  • Glycolysis then converts these 3 intermediates to pyruvate
38
Q

Wernicke-Korsakoff syndrome

A

Deficiency in thiamine pyrophosphate

Transketolocase is deactivated
People with this disease have ten times less TPP than normal

39
Q

Why are alcoholics more likely to have Wernicke-Korsakoff syndrome

A

Alcoholics have bad diets, which then lead to thiamine deficiency

40
Q

Symptoms of Wernicke Korsakoff

A

Neuro psychiatric

  • Eye movement paralysis
  • Poor guit (weird walking)
  • Memory and mental function decline

M2C Unit 2 Abali (5 decks)

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