Pentose Phosphate Pathway And NADPH Flashcards
What’s another name for Pentose Phosphate Pathway?q
Hexose MonoPhosphate (HMP) Shunt
PPP is a branch off of what pathway?
Glycolytic
PPP serves what two purposes? think about the other name.
Generation of NADPH (monophospate)
Generation of ribose, 5 carbon sugar (not a hexose)
The ribose generated from PPP with be used in what?
The synthesis of nucelotides (the five carbon sugar building block)
Will PPP always create both NADPH and ribose?
No, it can either one, both, or neither.
Dependent on needs of the cell.
In PPP, how much ATP is used/consumed?
None!
What are the two types of reactions in PPP?
Oxidative reactions and nonoxidative reactions
Irreversible reactions of PPP
Oxidative
Reversible reactions of PPP
Nonoxidative
Steps/reactions of PPP
- Dehydrogenation of G-6-P
- Hydrolysis of 6-phosphogluconate
- Oxidative decarboxylation of 6-phosphogluconate
4-8: Interconversions of sugar molecules
Dehydrogenation of G-6-P
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
What inhibits and upregulates step 1?
NADPH inhibits and Insulin upregulates
Hydrolysis to 6-phosphogluconate
step 2
Enzyme: 6-phosphogluconolactone hydrolase
irreversible
Produces one NADPH
Oxidative phosphorylation of 6-phosphogluconate
Step 3
Enzyme: 6-phosphogluconate dehydrogenase
Irreversible
Produces 1 NADPH
Interconversions of sugar molecules
Step 4-8
Enzyme: transketolase
Reversible steps
Interconverts sugars with 3 to 7 carbon atoms
Permit synthesis for ribose-5-p for nucleotide production
Transketolase
Enzyme for step 4-8, Interconversions of sugar molecules
Requires TPP
What is the significance of transketolase?
It is important in diagnosing thiamine deficiency
Done by measuring its activity in RBCs
What is the difference between NADH and NADPH?
There is a phosphate group on the ribose sugar of NADPH in the place of a hydroxyl group on a NADH
5 functions of NADPH
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
What is ROS?
Reactive oxygen species
When are ROS produced?
During aerobic metabolism
Through reactions with drugs and toxins
When levels of antioxidants are diminished
NADPH plays a key role in the neutralization of
ROS
NADPH role in neutralization of ROS
Assists in the reduction of GSSG to become GSH
Substrate in Glutathion, major antioxidant system
GSH will become reoxidized to convert ROS into water
NADPH role in the Cyt P450 System
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
Cytochromal P450 monooxygenase systems:
Or Cyt P450 for short
Mitochondrial and Micosomal
Cyt P450 in Mitochondrial system
Synthesis of steroids
Cyt P450 in microsomal system
Detoxification of foreign compounds
Mitchondrial Cyt P450 plays a key role in which tissues and organs?
Steroidogenic tissues (placenta, ovaries, testes, and adrenal cortex)
Liver
Kidney
Mitochondrial Cyt 450 in steroidogenic tissues
Uses NADPH for synthesis of steroid hormones
Mitochondrial P450 in the liver
Uses NADPH to synthesize bile acids and vitamins D3
Mitochondrial Cyt P450 in the kidney
Converts vitamin D3 to its active form
Where is the Microsomal Cyt P450 found?
Membranes of the smooth ER in liver cells
Detoxifies drugs toxins and other chemicals
NADPH plays a role in phagocytosis through what molecules?
Neutrophils and macrophages in WBCs
How does NADPH aid in phagocytosis?
The NADPH oxidase and myeloperoxidase are used to generate oxygen free radicals to aid in destruction of microorganisms
What is Chronic Granulomatous disease?
rare and genetic
NADPH oxidase deficiency, not able to produce oxygen free radicals.
What is NO?
NITRIC OXIDE
Not nitrous oxide. Idiot.
NO is synthesized from…
Arginine, oxygen, and NADPH
What is the biological role of NO?
Smooth muscle relaxant
Used by macrophages to generate free radicals to assist in killing microorganisms
Inhibits platelet aggregation
Functions as a neurotransmitter in brain
G6PD Deficiency
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
G6PD is symptomatic when..
There is an infection
There are drugs that produce an oxidative stress
Fava beans??
Clinical manifestation of G6PD Deficiency
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
Only way to make NADPH in RBCs
HMP Pathway (PPP)
NADPH production in cells other than RBCs
Other pathways contribute to production
RBCs do not have a
Nucleus (or mitochondria)
Since RBCs do not have a nucleus, they cannot:
Synthesize more G6PD to replace any that are lost, therefore is cannot be replaced during its short life cycle
What is the life cycle of a RBC?
110 days, about
Patient can overcome G6PD deficiency in RBCs if:
Oxidative stress is removed, since the RBCs can reproduce
G6PD Deficiency can produce what characteristic on RBCs?
Heinz bodies, little precipitates of oxidized hemoglobin on the RBC (almost looks like a exterior nucleus-shaped cyst)
