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42 Cards in this Set

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what are the 2 phases of pentose phosphate pathway?
phase 1 is oxidative
--makes NADPH
--turns glucose 6-phosphate into ribose 5-phosphate

phase 2 non-oxidative
--interconversion of 3,4,5,6 and 7 carbon sugars
what is ribose 5-Pi used for?
Component of RNA, DNA, ATP, NADH, FAD, Coenzyme A

fatty acid synthesis
cholesterol synthesis
neurotransmitter synthesis
What are the 5 carbon sugars used for?
nucleotide biosynthese

glycolytic pathway intermediates
Where does the pentose phosphate pathway take place?
cytoplasm

both pathways
How many molecules of NADPH are made in the oxidative phase?
2 molecules NADPH
what is the enzyme that catalyzes the conversion of glucose 6-pi to 6-phosphoglucono-d-lactone?
glucose 6-Pi dehydrogenase
what is the amount that the Km for NAD+ over NADP+ is for glucose 6-Pi dehydrogenase?
~1,000 times higher than NADP+

that means glucose-6Pi dehydrogenase is way specific for NADP+
Name the structures and the enzyme involved in this reaction
Structure 1 glucose 6 phosphate

enzyme is glucose 6-phosphate dehydrogenase

structure 2 is 6-phosphoglucono-b-lactone
what is the enzyme that converts 6-Phosphoglucono-b-lactone into 6-phosphogluconate?
lactonase
Name the structures and the enzyme
6-Phosphglucono-b-lactone

lactonase

6-phosphogluconate
what enzyme catalyzes the production of a 2nd NADPH from 6-Phosphogluconate?

What's end result?
6-phosphogluconate dehydrogenase

ribulose 5-Pi
What does phosphopentose isomerase do?
ribulose 5-Pi turns into ribose 5-Pi
What does phosphopentose epimerase do?
ribulose 5-Pi turns into xylulose 5-Pi
name the structures and the enzyme

What does phosphopentose isomerase and epimerase do to the product?
6-phosphogluconate

6-phosphogluconate dehydrogenase

ribulose 5-Pi

isomerase makes ribose 5-Pi

epimerase makes xylulose 5-Pi
what is the net result of the oxidative phase of pentose phosphate pathway?
for every glucose 6-Pi
2 NADPH are made + 1 ribose 5-Pi
which is more needed in the cells for biosynthesis, ribose 5-Pi or NADPH?

And what happens to the one we don't need as much?
NADPH

ribose 5-Pi is converted to GAP-3 and fructose 6-Pi via transketolase and transaldolase
what's the net result of transketolase and transaldolase reactions with ribose 5-Pi?
3 C5 <------> 2 C6 + C3

3 pentoses go to 2 hexoses and 1 triose
How are the pentose phosphate pathway and glycolysis linked?
Ribose 5-Pi is converted to GAP-3 via transketolase

C5 + C5 <------> C3 + C7
What is the first transketolase reaction?
xylulose 5-Pi + ribose 5-Pi <----> GAP-3 + sedoheptulose 7-Pi
What reaction does transaldolase catalyze?
GAP-3 + sedoheptulose 7-Pi <---> fructose 6-Pi and erythrose 4-Pi

C3 + C7 <----> C6 + C4
How is GAP-3 synthesized from erythrose 4-Pi and xylulose 5-Pi?
a second transketolase reaction

C4 + C5 <----> C3 + C6
If you have 3 ribose 5-Pi how many fructose 6-Pi and GAP-3 will you get?
2 fructose-6-Pi and 1 GAP-3
What is TPP?
thiamine pyrophosphate

accepts anion and releases aldose product which then condenses with 2-carbon glycoaldehyde unit to make a new ketose product
which residue on the Schiff base reacts with the ketose substrate?
Lys
How is the processing of whether or not Glucose 6-Pi goes to glycolysis or pentose phosphate pathway managed?
cytoplasmic concentration of NADP+ determines which route Glucose 6-Pi takes
Why is NADP+ a regulator in determining the fate of glucose 6-Pi?
it is the electron acceptor in pentose phosphate pathway so low levels of NADP+ in cytoplasm inhibits the dehydronation of Glucose-6-Pi.
How do excess amounts of NADPH inhibit the pentose phosphate pathway?
NADPH competes with NADP+ for the enzyme glucose 6-phospate dehydrogenase so when levels of NADPH are high it ensures we don't shuttle more glucose 6-pi to that pathway.
how is regulation of non-oxidative phase of penthose phosphate pathway controlled?
based on the availability of the substrates.

The main regulatory and rate determining step is the first one of NADP+ levels.
What's going to happen to Glucose 6-Pi if the body is sythesizing alot of nucleotide precursors of DNA in rapidly dividing cells?
It needs much more ribose 5-Pi than NADPH.

Glucose 6-Pi will do glycolytic pathway and transaldolase and transketolase will reverse their mechanisms to yield 3 Ribose 5-Pi from 2 fructose 6-Pi and GAP
What happens to Glucose 6-Pi if the needs for NADPH and ribose 5-Pi are balanced?
Good old fashioned pentose phosphate pathway occurs in which 2 NADPH molecules and 1 ribose-5-Pi are yielded
What happens to Glucose -6-Pi if the bod needs to make some serious fatty acids?
This requires way more NADPH. The Glucose-6-Pi will all go through the oxidative phase.
How does Glucose 6-Pi get fully oxidated?
3 reactions. First the normal pentose phosphate pathway yielding 2 NADPH and 1 ribose 5-Pi

The ribose 5-pi goes through the transketolase and transaldolase rxns to yield GAP and fructose 6-Pi and those 2 bad boys go through gluconeogenic pathway where it is recycled into Glucose 6-Pi
What if your body needs both ATP and NADPH? How does the Glucose-6-Pi get allocated?
After you do the pentose phosphate pathway, the ribose-5-Pi can be turned into pyruvate
What is the role of GSH?
reduced glutathione inhibits oxidative stress from oxidative metabolism

GSH becomes GSSG and then GSSG is reduced by NADPH
Explain why low levels of glucose 6-Pi dehydrogenase would be bad from a ROS standpoint.
glucose 6-Pi dehydrogenase is the rate-limiting enzyme involved in manufacturing NADPH in pentose Phosphate pathway.

If there is no NADPH generated because there is none of this enzyme then GSSG remains in its oxidated state and causes cellular damage.
name the 3 amino acids in the tripeptide glutathione
y-glutamylcysteinylglycine

y-glutamate
cysteine
glycine
what does pamaquine treat?

Why does it induce hemolytic anemia in some patients?
malaria

It causes hemolytic anemia in patients who have deficiency of glucose6-Pi dehydrogenase because the ratio of GSH is going to be screwy in the cell (because no NADPH to reduce GSSG to GSH) and cells will be prone to hemolysis
what is the mechanism reaction about how GSSG gets reduced via glutathione reductase?
2 GSH + ROOH----> GSSG + H20 + ROH
What does pamaquine generate?
peroxides ROOH
What are heinz bodies?
aggregates on cell plasma membranes of cross-linked Hb

They deform membranes, cause RBC lysis
What is the evolutionary advantage of a glucose 6-pi dehydrogenase deficiency?
protects against faciparum malaria

11% occurrence in Africans

Perhaps parasites require GSH and pentose phosphate pathway products for growth
name structures
enzymes and cofactors produced