Pentosephosphate Pathway Flashcards
______ is used for biosynthetic reactions to prevent ________ damage to cells and generate ________ for ______.
NADPH
Oxidative damage to cells
Reactive Oxygen Species for Phagocytosis
_____ is used for nucleotide biosynthesis.
Ribose
Pentose Phosphate Pathway is used as an alternate pathway for _______ and occurs in the ________.
Is it used to make ATP?
It consists of _____: ______ and _____.
glycolysis, cytosol
NO ATP production
Two Phases: Oxidative and Non-Oxidative
The oxidative phase of PPP is _________ and generates ________
IRREVERSIBLE
NADPH
ribulose-5-phosphate
CO2
The non-oxidative phase is _______ and converts ________ such as ________ to _________.
reversible
5-carbon sugars such as ribose-5-phosphate to fructose-6-phosphate
_________ and ________ are unique to the _________ phase of PPP.
______ requires _______.
Transketolase and transaldolase are unique to the non-oxidative phase of PPP
Transketolase- Thymine
Entry into the PPP is determined by the ratio of _____________.
NADP+ to NADPH
PPP is active in tissues that are __________, ________________ and ______.
Rapidly growing
actively synthesizing fatty acids, cholesterol,steroids
Exposed to O2
Ex. Bone Marrow, Skin, Intestinal Muscosa, Cancer Cells, Liver, RBC, cell of lens and cornea)
The oxidative phase is ________.
______ is oxidized to _________. Is ATP generated?
What are the by-products?
Irreversible
Glucose-6-phosphate is oxidized to Ribulose-5-phosphate
NO ATP
NADP+ ——–> NADPH x 2
CO2
Where does the NADPH generated from the oxidative PPP stage go?
Fatty Acid Synthesis
Cholesterol Synthesis
Glutathione Reduction
The carbon in the oxidative phase of PPP from Glucose-6-Phosphate is released as ______.
CO2
The non-oxidative phase of PPP involves either the release of __________ or the conversion of it to ___________.
The whole purpose of the non-oxidative phase of PPP is to ________________.
Ribulose-5-Phosphate
Fructose-6-Phosphate
Convert between 5 and 6 carbon sugars
The oxidative phase converts ____________ to _________.
The non-oxidative phase converts ____________ to _________.
Glucose-6-Phosphate to Ribulose-5-Phosphate
Ribulose-5-Phosphate to Fructose-6-Phosphate
If the ribose-5-phosphate is released from the PPP, what is its fate?
Make
Nucleotides
Coenzymes (ATP,NADH,FADH2, CoA)
The first step of PPP in the oxidative stage is the conversion of ________ to _________ using the enzyme __________.
__________ is made as well.
A series of _______ enzyme reactions takes place before the final product, ___________, is produced.
_________ and ______ are released in the ______ enzyme reaction
Glucose-6-Phosphate to 6-Phosphoglucono-delta-lactone using the G6P DEHYDROGENASE enzyme.
NADPH is made
2 more , Ribulose-5-Phosphate
NADPH and CO2 are released in the final.
H+ is released as the result of a hydration reaction in the 3rd.
What is the rate-limiting step of PPP?
It is the _______ step. The only way to increase the rate of the oxidative PPP reaction is to __________.
Step 1
Convert Glucose-6-Phosphate to 6-Phosphoglucono-delta-lactone
via
G6P DEHYDROGENASE enzyme
RATE-LIMITING ; increase the rate of the first step
What is the role of G6P DEHYDROGENASE enzyme in PPP?
Convert Glucose-6-Phosphate
to
6-Phosphoglucono-delta-lactone
in the 1st step of the oxidative phase of PPP.
What is the difference between NAD+ and NADP+?
NAD+ has a OH group on the 2’ Carbon
NADP+ has a Phosphate
What are the similarities between NAD+ and NADP+?
Everything including the Adenine group with the EXCEPTION of the 2’ carbon which consists of and OH and a phosphate for NAD+ and NADP+ respectively.
There is more ______ plus in the cytosol and more ________.
NAD+/NADH
NAP+/NADPH
NAD+ inside cell
NADPH
What are the functions of NADPH?
- Reductive biosynthesis of fatty acids, cholesterol and steroids, nucelotides
- Detoxification by reduction of oxidized gluthationine which scavenges ROS
Cytochrom P450 monooxygenase
- Phagocytosis
NADPH Oxidase generates ROS to help kill pathogens.
NADPH can detoxify by reducing _________ which ________.
NADPH also plays a role in phagocytosis by ________.
Oxidized gluthathione which scavenges ROS
Generating ROS as NADPH Oxidase
The non-oxidative phase of the PPP involves the creation of __________ from ________ via the enzymes ________.
Glyceraldehyde-3-phosphate and Fructose-6-phosphate from 2 5-carbon sugars via the enzymes transketolase and transaldolase.
Ribose-5-phosphate - 5 carbon sugar
A minor portion of the O2 we consume is converted to ____________ when ________ accepts ___________.
___________ can be reduced to other reactive species such as _____ and _______.
damaging ROS when O2 accepts electrons
Superoxide O2- can be reduced to other reactive species such as H2O2 and OH-
ROS is produced as a result of _______________.
- enzymatic reaction by-product
- Physiological products
- Ionizing radiation
- Sulfa Drugs
- Antimalarials
- Fava Beans
ROS can be combatted by ____________ which requires ________ to regenerate.
Where can we get the regeneration compound?
Glutathione GSH
NADPH
PPP
Describe the structure of glutathione.
Glutathione is a tripeptide with a marker cysteine AA with a thiol group.
When two glutathione molecules are oxidized, what happens?
They will form a di-sulfide bond at the sulfide groups on the cysteine residues.
When cysteine is reduced _______ is also reduced.
Glucothione
- O2 reacts with substances that give up e- and create a ________
- ________ uses ______ to convert ________ into ______.
- In the process of removing peroxidases, Gluthathione becomes ______.
- __________ oxidizes one molecule of ______ to turn ______ into _______.
ROS
Glutathione Perioxidase uses reduced Glutathione to convert H2O2 into H2O
oxidized
Glutathione Reductase oxidizes one molecule of NADPH to NADP+ to turn oxidized Glutathione back to the reduced form.
What catalyzes the rate-limited step in the oxidative stage of the PPP?
Glucose-6-Phosphate Dehydrogenase
What are clinical manifestations of G6PD reduction ?
- Hemolysis of RBC due to inability to produce adequate amounts of NADPH which is needed to scavenge ROS
The presence of Glucose-6-Phosphate Dehydrogenase has an health benefit. What is it?
Reduced malaria growth
What are the most important pathways of carbohydrate metabolism in erythrocytes ?
Anaerobic Glycolysis
PPP
Generation of 2,3 BPG
Reactive oxygen species can cause _________ peroxidation which results in _______ and thus ______.
lipid, leaky membrane
Hemolysis
ROS is generated from the ___________ oxidation of _________ to _______.
Explain this process.
non-enzymatic of Hb to Met Hb
Oxygen steals an electron from the Fe in heme making it unable to carry Oxygen.
If ________ is defective, NADPH is reduced.
How does this impact ROS species?
Glucose-6-Phosphate Dehydrogenase
ROS Increases
G6Pdehydrogenase is responsible for the oxidative reaction step of PPP that produced NADPH. NADPH is required to turn oxidized Glucothionine into the reduced form to turn peroxides into water.
The lack of __________ results in a lack of NADPH. This reduces the number of ____________ available to _________.
Glucose-6-Phosphate Dehydrogenase, NADPH
Reduced Glucothionine molecules available to break down peroxides (ROS) to water
Phagocytic cells in response to an infectious agent rapidly consume ________ to produce _____ which aid in ______.
O2, ROS which aid in killing pathogens,
When phagocytic cells rapidly consume ______ to produce _______, what is it called?
What catalyzes it?
Respiratory Burst
NADPH Oxidase
The respiratory burst of phagocytic cells increases ________ consumption and ______shunt.
O2 and PPP
The PPP provides the _________ for _________ of phagocytic cells.
NADPH for the respiratory burst
- The pathogen binds _______.
2._______ is activated
- _______ reduces ______ to make superoxides and ROS’s
- _______ provides for_____________ and generation of ROS.
- The pathogen binds to the phagocyte.
- NADPH oxidase is activated
- NADPH reduces O2 to make superoxides and ROS’s
- PPP provides NADPH oxidase and generation of ROS.
UDP-glucose is a _________ that can be _______ to UDP-________.
Glucose Donor
Epimerized
UDP-Galactose
UDP-glucose can be oxidized to a __________.
sugar acid, glucuronic acid
____________ transfer sugar from UDP-sugars to ___________ amino acids (2) in proteins.
Glycosyltransferases
nucleophilic amino acids - Serine and Asparagine
UDP-Glucuronate is the same thing as ________ and is important for __________.
Glucuronic Acid
DRUG detoxification and excretion of BIIRUBIN
What is biliruben?
A breakdown product of Hb
UDP-Glucose is ______ to UDP-Glucuronate by ________ which also produces ________.
oxidized by UDP-glucose dehydrogenase
2 NADH
UDP-glucuronate can donate _________ to other ____ containing compounds to make _______.
This is what breaks down products such as ________ or ______.
Glucuronic acid to other -OH containing compounds to make glucuonide
biliruben or steroids
The ______ of UDP-Glucose to ______ results in a _______ charged ______ group which ______ water solubility of _______ compounds that can be __________.
oxidation of UDP-Glucose to UDP-Glucuronate
negatively charged , carboxyl group which increases water solubility of NON-POLAR compounds that can be excreted in urine or bile.
UDP-glucuronate can also make ________.
Proteoglycans, glycoproteins which are an important component of cartilage and ECM
How does galactose enter glycolytic pathway?
Galactose can be converted to UDP-glucose of Glucose-6-P
How does fructose enter glycolytic pathway?
Fructose can be cleaved and enter the glycolytic pathway as DHAP and Glyceraldehyde-3-Phosphate.
Where does fructose usually enter glycolytic pathway?
LIVER
Galactose Metabolism
- Galactose is a _________ by _________ to _______.
- Galactose is phosphorylated by Galactokinase to Galactose-1-Phosphate.
- Galactose-1-Phosphate will interact with UDP glucose to make Glucose-1-P and enter the glycolytic pathway.
Fructose is a component of the disaccharide ________.
It can be synthesized from glucose via the ________ pathway and is metabolized to __________ in the _____.
Sucrose
Polypol , glycolytic intermediate in the liver
Fructose metabolism occurs in the _______ and bypasses __________.
Liver
Bypasses key regulatory steps in glycolysis
Fructose will be phosphorylated to __________by _________ which is MUCH faster than ________.
Bypassing _________, ______ converts _______- to ________ and _______.
Fructose-1-Phosphate by Fructokinase which is much faster than glucokinase
PFK-1 ; the key regulatory step in glycolysis , converts fructose-1-P to glyceraldehyde and DHAP
Describe the ATP feedback of fructose metabolism.
There is none!
As we consume fructose, we use up ATP which generates the glycolytic cycle run . Pyruvate will be formed in excess and converted to lactate to will enter TCA to make citrate
High levels of ________can lead to _________, ________ and _________ in the liver.
Fructose , liver damage, lactic acidosis, fatty acid synthesis in the liver
What is the polyol pathway?
The pathway used to synthesize fructose.
Polyol Pathway
- Sugars are reduced to _________ called _______ by ___________.
________ is consumed
- _________ is converted to_______ which cannot be transported by _________.
- Build up of _______ and consumption _______ in ____________ may lead to ___________ in diabetics.
Polyol Pathway
- Sugars are reduced to sugar alcohols called sorbitol by aldose reductase.
NADPH is consumed
- Sorbitol is converted to fructose which cannot be transported by GLUTs.
- Build up of sorbitol and consumption of NADPH in lens, nerve and glomerulus may lead to tissue damage in diabetics.
Sorbitol accumulation can lead to _________.
- Decrease in NADPH
- Accumulation of ROS
- Increased osmotic pressure
- Glycation of lens leads to cataract (cloudiness)
