Pentose Phosphate Pathway

Front 1

What chronic pathologies can cause oxidant stress to erythrocytes?

Back 1

1. hypercholesterolemia
2. hypertension
3. diabetes

Front 2

What drugs/toxins can cause high levels of erythrocyte oxidative stress?

Back 2

antimalarial drugs such as primaquine

Front 3

What is the important amino acid in glutathione that has a thiol side-chain?

Back 3

Cysteine

Front 4

What effect does oxidizing a thiol residue have on enzyme function?

Back 4

Inactivates the enzyme, and oxidizing a enzyme too much results in permanent activation of the enzyme

Front 5

What is the function of superoxide dismutase?

Back 5

Removes free oxygen radicals from circulation by turning them into H2O2, so the higher the superoxide dismutase concentration the more free radicals are removed from circulation

Front 6

Why is H2O2 a problem?

Back 6

B/c in the presence of Fe(II) H2O2 is cleaved to form OH* radicals which are extremely dangerous

Front 7

How is H2O2 broken down in RBCs?

Back 7

By catalase which breaks H2O2 into H2O/O2

Front 8

What superoxide dismutase mutation is present in RBCs?

Back 8

SOD1 b/c it is present in the cytoplasm, whereas SOD is present in the mitochondria and extracellular in SOD2 and SOD3 respectively

Front 9

What does SOD1 mutation cause?

Back 9

Cytoplasmic and caused by Cu and Zn cofactors which cause amylotropic lateral sclerosis 1

Front 10

What enzyme uses glutathione to oxidize H2O2 thus providing another pathway to remove H2O2?

Back 10

Glutathione peroxidase

Front 11

What enzyme regenerates glutathione, GSH using NADPH?

Back 11

Glutathione reductase

Front 12

What can cause early aging due to decreased activity of dismutase and catalase?

Back 12

Inability to remove H2O2

Front 13

What effect do oxidized carbohydrates for aldehydes have?

Back 13

React w/ neutrophils on proteins and nucleic acids

Front 14

What effect do oxidizing lipids have?

Back 14

alter membrane properties and react w/ proteins and nucleic acids

Front 15

What pathway generates NADPH that is used to remove ROS's?

Back 15

Pentose Phosphate Pathway -aka- "hexose monophosphate shunt"

Front 16

What is the importance of ribose-5-phosphate?

Back 16

Important in DNA synthesis

Front 17

Where is ATP used in the pentose phosphate pathway?

Back 17

NO ATP IS USED!!!

Front 18

What is the rate-limiting reaction in the pentose phosphate pathway?

Back 18

G6P dehydrogenase, which is also the first step

Front 19

What steps in the PPP generate NADPH?

Back 19

1. G6P dehydrogenase/ 6-phosphogluconolactone hydrolase
2. 6-phosogluconolactone hydrolase

Front 20

What glycolytic intermediates are generated by the PPP?

Back 20

glyceraldehyde-3-phosphate and fructose-6-phosphate

Front 21

What intermediate that is generated by the PPP can be used as a glycolytic intermediate or can be recycled into the PPP to make NADPH or ribose-5-phosphate?

Back 21

fructose-6-phosphate

Front 22

What intermediate generated by the PPP will only go forward through glycolysis?

Back 22

Glucose-3-phosphate

Front 23

What intermediates that are generated by the PPP are not useful and must be converted to other metabolites in order to be useful?

Back 23

1. xylulose 5 phosphate,
2. sedoheptulose 7 phosphate
3. ribose 5 phosphate

Front 24

How do cells w/ Glucose 6 phosphate dehydrogenase deficiency make ribose 5 phosphate?

Back 24

By going backwards through the PPP using glycolytic intermediates glyceraldehyde 3 phosphate and fructose 6 phosphate

Front 25

What is the rate-limiting step in the PPP?

Back 25

Glyceraldehyde 6 phosphate dehydrogenase

Front 26

What symptom is present in pts w/ the G6PD Variant?

Back 26

hereditary non spherocytic hemolytic anemia

Front 27

What is the interaction that can happen b/e the active site of heme and nitric oxide?

Back 27

NO can interact w/ the active site of the RBC to create a molecule of nitrate, which oxidizes the Fe group on the RBC to the Fe(III) state

Front 28

What is heme Fe(III) called? what are this molecule's special characteristics?

Back 28

Methemoglobin, which cannot bind oxygen

Front 29

What molecule is generated by interaction of superoxide and nitric oxide?

Back 29

A short-lived species called peroxide nitrite (ONOO) which can cause huge damage during its lifespan

Front 30

What reaction does superoxide dismutase accelerate?

Back 30

The middle reaction

Front 31

What is the good and the bad about vitamin C (Ascorbic acid)?

Back 31

It is an antioxidant, which is GOOD but it also converts Fe(III) to Fe(II) which is good and bad, its good b/c it reduces the Fe BUT it is bad b/c it breaks Fe(II) can react w/ H2O2 to generate OH* radicals which also creates Fe(III) AGAIN which then goes on and is reduced by Vit. C to Fe(II) repeating the cycle of death

So if you have a dz that causes Fe(III) to be released into circulation it can react w/ ascorbic acid and cause this cycle

Front 32

What causes old RBCs to be recognizable by the spleen?

Back 32

Damage to RBC membranes caused by interaction w/ free radicals

Front 33

What enzyme converts methemoglobin to hemoglobin?

Back 33

Methemoglobin reductase

Front 34

What cofactor does methemoglobin reductase require to function?

Back 34

NADH

Front 35

What does NO react with in blood?

Back 35

oxidized hemoglobin in the RBC to form nitrite, which is part of normal detoxification of nitric oxide

Front 36

What slows down the NO breakdown to nitrite w/in RBCs?

Back 36

The membrane of RBCs and the packaging of iron w/in the globin molecule so this slows down the creation of methemoglobin

Front 37

Where do RBCs get the NADH used to breakdown methemoglobin?

Back 37

From glycolysis, but pyruvate conversion to lactate also uses NADH to regenerate NAD+ for glycolysis. SO the RBC must decide whether to have NADH used to make lactate or to use it to remove methemoglobin

Front 38

What is the function of methylene blue?

Back 38

Methylene blue is reduced by NADPH to breakdown methemoglobin and create leukomethylene blue

Front 39

What side-effect of methylene blue can cause anemia?

Back 39

If a pt cannot make NADPH then methylene blue will reverse and convert normal Hb(FeII) to methemoglobin and leukomethylene blue so anemia will be accelerated

Pts that cannot make NADPH are pts that have G6P dehydrogenase deficiencies

Front 40

Why do Fava beans cause anemia?

Back 40

Fava beans act like methylene blue, so pts who have G6P dehydrogenase deficiencies will cause hemoglobin to be converted to methemoglobin, causing anemia

Front 41

What reaction commits glucose to go down glycolysis?

Back 41

PFK which converts fructose-6-phosphate to fructose-1,6-bisphosphate

Front 42

How does the RBC decide whether to use glucose to go down the PPP or through glycolysis?

Back 42

PFK is the commiting step of glycolysis, but when it binds to band 3 protein it deactivates the PFK. So G6P will go through the PPP and glucose will be used for its antioxidant properties. this occurs when oxygen is bound.

When hemoglobin is unbound PFK is not bound to band 3 protein and so glucose goes through glycolysis and not the PPP. So a low-oxigenation state glucose goes through glycolysis, but in a high-oxidative state there is the possibility of making free-radicals and so glucose goes through the PPP to generate free-radical fighting chemicals.

Front 43

If you don't have NADPH what will build up and cause cellular damage?

Back 43

OH*