Pentose Phosphate Pathway And NADPH

Question 1

What’s another name for Pentose Phosphate Pathway?q

Answer 1

Hexose MonoPhosphate (HMP) Shunt

Question 2

PPP is a branch off of what pathway?

Answer 2

Glycolytic

Question 3

PPP serves what two purposes? think about the other name.

Answer 3

Generation of NADPH (monophospate)

Generation of ribose, 5 carbon sugar (not a hexose)

Question 4

The ribose generated from PPP with be used in what?

Answer 4

The synthesis of nucelotides (the five carbon sugar building block)

Question 5

Will PPP always create both NADPH and ribose?

Answer 5

No, it can either one, both, or neither.

Dependent on needs of the cell.

Question 6

In PPP, how much ATP is used/consumed?

Answer 6

None!

Question 7

What are the two types of reactions in PPP?

Answer 7

Oxidative reactions and nonoxidative reactions

Question 8

Irreversible reactions of PPP

Answer 8

Oxidative

Question 9

Reversible reactions of PPP

Answer 9

Nonoxidative

Question 10

Steps/reactions of PPP

Answer 10

1. Dehydrogenation of G-6-P
2. Hydrolysis of 6-phosphogluconate
3. Oxidative decarboxylation of 6-phosphogluconate
   4-8: Interconversions of sugar molecules

Question 11

Dehydrogenation of G-6-P

Answer 11

Step 1

Enzyme: g6p dehydrogenase (G6PH)

Rate limiting step

Major point of regulation

NAPH+ is a required coenzyme

NADPH is POTENT competitive inhibitor

Unregulated by insulin

Question 12

What inhibits and upregulates step 1?

Answer 12

NADPH inhibits and Insulin upregulates

Question 13

Hydrolysis to 6-phosphogluconate

Answer 13

step 2

Enzyme: 6-phosphogluconolactone hydrolase

irreversible

Produces one NADPH

Question 14

Oxidative phosphorylation of 6-phosphogluconate

Answer 14

Step 3

Enzyme: 6-phosphogluconate dehydrogenase

Irreversible

Produces 1 NADPH

Question 15

Interconversions of sugar molecules

Answer 15

Step 4-8

Enzyme: transketolase

Reversible steps

Interconverts sugars with 3 to 7 carbon atoms

Permit synthesis for ribose-5-p for nucleotide production

Question 16

Transketolase

Answer 16

Enzyme for step 4-8, Interconversions of sugar molecules

Requires TPP

Question 17

What is the significance of transketolase?

Answer 17

It is important in diagnosing thiamine deficiency

Done by measuring its activity in RBCs

Question 18

What is the difference between NADH and NADPH?

Answer 18

There is a phosphate group on the ribose sugar of NADPH in the place of a hydroxyl group on a NADH

Question 19

5 functions of NADPH

Answer 19

EERPS

Electron donor for reductive biosynthesis of FAs, cholesterol and steroids

Electron donor for neutralization of reactive O species (h202, superoxide, etc)

Provides reducing equivalents for cytochrome systems

Plays role in phagocytosis

Substrate for synthesis of NO

Question 20

What is ROS?

Answer 20

Reactive oxygen species

Question 21

When are ROS produced?

Answer 21

During aerobic metabolism

Through reactions with drugs and toxins

When levels of antioxidants are diminished

Question 22

NADPH plays a key role in the neutralization of

Answer 22

ROS

Question 23

NADPH role in neutralization of ROS

Answer 23

Assists in the reduction of GSSG to become GSH

Substrate in Glutathion, major antioxidant system

GSH will become reoxidized to convert ROS into water

Question 24

NADPH role in the Cyt P450 System

Answer 24

Rxn:
R-H + O2 + NADPH + H -> R-OH + H20 + NADP+

Assists in cleaving O2 to create water and hydroxyl group on R group

By adding oxygen, the compound may be inactivated, made more soluble, or provide a reactive group for attachment of other compounds

Question 25

Cytochromal P450 monooxygenase systems: Or Cyt P450 for short

Answer 25

Mitochondrial and Micosomal

Question 26

Cyt P450 in Mitochondrial system

Answer 26

Synthesis of steroids

Question 27

Cyt P450 in microsomal system

Answer 27

Detoxification of foreign compounds

Question 28

Mitchondrial Cyt P450 plays a key role in which tissues and organs?

Answer 28

Steroidogenic tissues (placenta, ovaries, testes, and adrenal cortex) Liver Kidney

Question 29

Mitochondrial Cyt 450 in steroidogenic tissues

Answer 29

Uses NADPH for synthesis of steroid hormones

Question 30

Mitochondrial P450 in the liver

Answer 30

Uses NADPH to synthesize bile acids and vitamins D3

Question 31

Mitochondrial Cyt P450 in the kidney

Answer 31

Converts vitamin D3 to its active form

Question 32

Where is the Microsomal Cyt P450 found?

Answer 32

Membranes of the smooth ER in liver cells Detoxifies drugs toxins and other chemicals

Question 33

NADPH plays a role in phagocytosis through what molecules?

Answer 33

Neutrophils and macrophages in WBCs

Question 34

How does NADPH aid in phagocytosis?

Answer 34

The NADPH oxidase and myeloperoxidase are used to generate oxygen free radicals to aid in destruction of microorganisms

Question 35

What is Chronic Granulomatous disease?

Answer 35

rare and genetic NADPH oxidase deficiency, not able to produce oxygen free radicals.

Question 36

What is NO?

Answer 36

NITRIC OXIDE Not nitrous oxide. Idiot.

Question 37

NO is synthesized from...

Answer 37

Arginine, oxygen, and NADPH

Question 38

What is the biological role of NO?

Answer 38

Smooth muscle relaxant Used by macrophages to generate free radicals to assist in killing microorganisms Inhibits platelet aggregation Functions as a neurotransmitter in brain

Question 39

G6PD Deficiency

Answer 39

inability to detoxify oxidizing agents Gene is on the x-chromosome One of most common single gene disorders Most common in African, Mediterranean, and Asian Some protecting against malaria (like sickle-cell and thalassemia) 11% of African Americans

Question 40

G6PD is symptomatic when..

Answer 40

There is an infection There are drugs that produce an oxidative stress Fava beans??

Question 41

Clinical manifestation of G6PD Deficiency

Answer 41

Almost exclusively in RBCs as an episodic hemolytic anemia in adults Neonatal jaundice in newborns (increased production of unconugated bilirubin) Other organs/tissues may be affected by hemolytic anemia Shorten lifespan in severe form

Question 42

Only way to make NADPH in RBCs

Answer 42

HMP Pathway (PPP)

Question 43

NADPH production in cells other than RBCs

Answer 43

Other pathways contribute to production

Question 44

RBCs do not have a

Answer 44

Nucleus (or mitochondria)

Question 45

Since RBCs do not have a nucleus, they cannot:

Answer 45

Synthesize more G6PD to replace any that are lost, therefore is cannot be replaced during its short life cycle

Question 46

What is the life cycle of a RBC?

Answer 46

110 days, about

Question 47

Patient can overcome G6PD deficiency in RBCs if:

Answer 47

Oxidative stress is removed, since the RBCs can reproduce

Question 48

G6PD Deficiency can produce what characteristic on RBCs?

Answer 48

Heinz bodies, little precipitates of oxidized hemoglobin on the RBC (almost looks like a exterior nucleus-shaped cyst)