Pentose Phosphate Pathway

Question 1

The pentose phosphate pathway provides a major source of what compound?

Answer 1

NADPH

Question 2

This pathway will also provide what sugar for the synthesis of ribonucleotides?

Answer 2

Ribose-5-phosphate

Question 3

The oxidative portions of the pentose pathway have how many reactions that lead to the formation of ribulose-5-phosphate?

Answer 3

Three

Question 4

The oxidative portion of the pentose pathway will produce what products (3) for each molecule of glucose-6-phosphate oxidized?

Answer 4

Ribulose-5-phosphate
CO2
two molecules of NADPH

Question 5

This pathway is important for what 3 processes in the body?

Answer 5

1. NADPH - dependent synthesis of fatty acids
2. NADPH - dependent synthesis of steroid hormones
3. Erythrocytes which require NADPH to keep glutathione reduced.

Question 6

NADPH-dependent synthesis of fatty acids is important in what parts of the body?

Answer 6

Liver, mammary glands, and adipose

Question 7

Synthesis of steroid hormones is important for what structures in the body?

Answer 7

Testes, ovaries, adrenal cortex, and placenta.

Question 8

Where does the oxidative stage of the pentose pathway occur in the cell?

Answer 8

Cytosol

Question 9

Glucose 6 phosphate dehydrogenase will catalyze an irreversible oxidation of glucose 6 phosphate into ______.

Answer 9

6-phosphogluconolacetone

Question 10

The dehydrogenation of glucose 6-phosphate needs a specific coenzyme what is it?

Answer 10

NADP+

Question 11

What will inhibit the dehydrogenation of glucose 6-phosphate?

Answer 11

NADPH

Question 12

What hormone up regulates the dehydrogenation of glucose-6 phosphate to 6-phosphogluconolacetone? Is this step rate limiting?

Answer 12

Insulin - yes it is rate limiting

Question 13

What does 6-phosphogluconaolacetone hydrolyze to?

Answer 13

6 phosphogluconate

Question 14

6 phosphogluconate is than converted to what sugar? What other compounds are released during this run?

Answer 14

ribulose 5-phosphate, CO2 and NADPH

Question 15

In what cell types does the non-oxidative reactions of the pentose pathways take place?

Answer 15

ALL cell types synthesizing nucleotides and nucleic acids.

Question 16

The reversible reactions permit ribulose-5-phosphate to be converted to what 3 compounds?

Answer 16

1. Ribose 5-phosphate
2. fructose 6-phosphate
3. glyceraldehyde 3-phosphate

Question 17

How does NADP+ differ from NAD+?

Answer 17

The presence of a phosphate group on one of the ribose subunits.

Question 18

The high energy electrons of NADPH will be used for what function in the cell?

Answer 18

Reducing equivalence

Question 19

What reactive oxygen species (ROS) is formed from the partial reduction of molecular oxygen?

Answer 19

Hydrogen peroxide

Question 20

The highly reactive species of free radicals can cause what type of damage to the body?

Answer 20

Damage to DNA, proteins, lipids leading to cellular damage and death.

Question 21

What is present in most cells that can chemically detoxify hydrogen peroxide?

Answer 21

Reduced Glutathione, a tripeptide-thiol

Question 22

What is Glutathione composed of?

Answer 22

Glutamate, cysteine and glycine

Question 23

Once Glutathione is oxidized to detoxify hydrogen peroxide how is it rejuvenated?

Answer 23

NADPH with the enzyme glutathione reductase.

Question 24

What does the breakdown of hydrogen peroxide by glutathione produce as end products?

Answer 24

2 water molecules and a dimerized glutathione

Question 25

What is the main function of the mitochondrial cytochrome P450 monoxygenase system and where is it found in the cell?

Answer 25

Associated with the synthesis of steroid hormones. Found on the inner mitochondrial membrane.

Question 26

More specifically, the P450 is used to hydroxylate intermediates for what biosynthetic process? Where especially does this occur in the body?

Answer 26

For the conversion of cholesterol to steroid hormones a process that make these compounds more water soluble. - placenta, ovaries, testes, and adrenal cortex

Question 27

In the liver what is the job of the P450 system?

Answer 27

To hyroxylate intermediates in bile acid synthesis, and the synthesis of Vit D3

Question 28

What does the endoplasmic reticulum especially in the liver contain? What is it's function?

Answer 28

Cytochrom P450 monooxygenase - to detoxify foreign compounds such as drugs, pollutants and pesticides.

Question 29

Describe Phase 1 Metabolism

Answer 29

- Microsomal system hydroylates these compounds (drugs, pollutants...etc) using NADPH as the source of reducing equivalents. - The hydroxylation may inactivate the compound and make them more soluble for excretion in the urine.

Question 30

What takes place in Phase 2 Metabolism

Answer 30

- Adding glucuronic acid or other compounds at the hydroxyl group further inactivating and/or increasing the water solubility of the compound.

Question 31

WBC can use what two types of methods to kill bacteria?

Answer 31

Oxygen dependent or non-oxygen dependent methods.

Question 32

In the oxygen dependent system what molecule is created by the activation of NADPH oxidase located in the cellular membrane of the phagocyte?

Answer 32

Superoxide

Question 33

What do we call the rapid consumption of the molecular oxygen that accompanies the creation of superoxide?

Answer 33

Respiratory burst

Question 34

What does the body do with the superoxide?

Answer 34

Either converts it to hydrogen peroxide spontaneously or through an enzyme superoxide dismutase.

Question 35

Superoxide can also spontaneously break down to what compound?

Answer 35

Hydroxy radical (OH)

Question 36

Hydrogen peroxide can also be converted into what effective bacteria killing liquid when combined with chlorine?

Answer 36

Hypochlorous acid

Question 37

What can lead to granulomatous disease?

Answer 37

Genetic deficiency of NADPH oxidase.

Question 38

What is the pathology of granulomatous disease?

Answer 38

Some bacteria are not completely destroyed and severe chronic infection develops. Granulomas are formed that sequester bacteria.

Question 39

What is an additional function of NADPH when it is combined with arginine and O2?

Answer 39

Synthesis of Nitric Oxide

Question 40

What is the most common disease producing enzyme abnormality in humans affecting 1 out of 400 individuals?

Answer 40

Glucose 6-phosphate deficiency G6PD

Question 41

G6PD is an inherited disease characterized by what pathology?

Answer 41

hemolytic anemia - which is caused by an inability to detoxify oxidizing agents.

Question 42

What chromosome is G6PD linked to?

Answer 42

X

Question 43

Why did G6PD develop?

Answer 43

It gave survival advantage to female carriers by giving resistance to falciparum malaria.

Question 44

Diminished G6PD activity impairs the ability of the cell to do what essential metabolic process?

Answer 44

To form the NADPH that is essential for the maintenance of the reduced glutathione pools. The result is a decrease in cellular detoxification of free radicals and peroxides.

Question 45

Glutathione also has an important role in proteins. Please explain.

Answer 45

Helps maintain the reduced states of sulfhydral groups in proteins including hemoglobin. Oxidation of these groups results in the denaturization of proteins.

Question 46

What can trigger symptoms in G6PD in ppl who don't normally show clinical symptoms?

Answer 46

Oxidant drug, fava beans or infection.

Question 47

What drugs can induce hemolytic anemia?

Answer 47

Antibiotics, antimalarials, and antipyretics. AAA