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52 Cards in this Set

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what is the role of NADPH in metabolism?
1)biosynthetic reactions
2)maintains a reducing environment in cells
3) maintenance of cell redox status and viability
more NAD+ or NADH in the cell?
NAD+ (700/1)
....NADH is used up very fast to make ATP
more NADP or NADPH in the cell?
NADPH (70/1)
...main job is reducing
another name for Pentose Phosphate Pathway
Hexose Monophosphate Shunt
the business end of NADPH
Nicitidimide (if reduced is NADPH if oxidzed is NADP)
where does the Pentose Phosphate Pathway occur?
in the cytosol
where is NADPH used in the body?
1)liver for detoxification
2)mammary glands (make lipids)
3)adipose tissues (make lipids)
4)adrenal cortex (makes steroids)
where NADPH is specifically required in the adrenal cortex?
for the nicrosomal 450 Monoxygenase System
What is the IMPORTANT molecule that NADPH keeps reduced??
glutathione (GSH)
What is Glutathione (GSH)?
An antioxidant that reduces PROTEIN DISULFIDES non enzymatically, reduces hydrogen peroxide and organic peroxides
what is the enzyme that GLUTATHIONE uses to reduce hydrogen peroxides and peroxides?
GLUTATHIONE PEROXIDASE
what is the product when Glutathione (GHS) redueces other compounds?
GSSG (GLUTATHIONE DISULFIDE)
Why is NADPH neccessary for Glutathione (GSH) activity?
It reduces Glutathionine Disulfide (GSSG) back to Glutathionine (GSH)
how is Pentose Phosphate Pathway involved in biosynthesis?
It generates 5-C sugars for nucleotide synthesis
2 Stages of Pentose Phosphate pathway in forming new sugars
1) G6P is oxidized to Ribulose-5-Phosphate (generates 2 NADPH and CO2)

2) Series of interconversions combine sugars of different carbon lengths to form products that can enter glycolysis
The 4 pathways that G6P can take
1)glycogen
2)back to glucose in liver and kidney
3)glycolysis
4)Pentose Phosphate Pathway
what is generated when G6P is converted to Rubulose 5P?
NADPH
What is G6P first converted to and by what enzyme?
6 Phosphoglucno Lactone
by glucose-6-Phosphate Dehydrogenase
which step is the COMMITTED STEP for the Pentose Phosphate Pathway?
conversion of G6P to the Lactone (6-Phosphoglucnolactone)
what controlls teh committed step of the Pentose Phosphate Pathway?
substrate availability of NADP+
Second step in Pentose Phosphate? Enzyme Number 2?
6-Phosphogluconolactone Hydrolase opens up the lactone ring to yield 6-PHOSPHOGLUCONATE
Third step in Pentose Phosphate?
Enzyme number 3?
6-PHOSPHOGLUCANATE DEHYDROGENASE produces RUBULOSE 5 Phosphate
What is produced when 6-Phosphoglucanate is converted to Rubulose 5 Phosphate?
NADPH and CO2
Where is a Beta Keto Acid formed in Pentose Phosphate Pathway?
in the step where 6-Phosphoglucanate Dehydrogenase converts phosphoglucanate to Ribulose 5 Phosphate
What happens then B Keto acid forms?
Decarboxylats and releases CO2
Will also see B Keto Acid with this enzyme in TCA cycle
Isocitrate Dehydrogenase
Ribulose 5 Phosphate is in equillibrium with what two other sugars?
1) Ribose 5 Phosphate
2) Xylulose 5 Phosphate
what converts Ribulose 5 Phosphate to Ribose 5 Phosphate? What intermediate is formed?
PHOSPHOPENTOSE ISOMERASE
Enediol intermediate
What enzyme converts Ribulose 5 Phosphate to Xylulose 5P?
PHOSPHOPENTOSE EPIMERASE
How does TRANSKETOLASE work?
Moves a 2C Keto fragment from a KETOSE DONAR to and ALDOSE ACCEPTOR
What configuration must the sugar be in in order for transketolase to work?
L configuration
What is the tightly bound cofactor that TRANSKETOLASE requires?
THIAMINE PYROPHOSPHATE
How does transketolase work?
Forms a carbanion = strong nucleophile that attaches the carbonyl C of the 2C fragment transferred
What is the role of TRANSALDOLASE?
Transfers 3C Keto fragment bwetween a Ketose and an Aldose Acceptor
what is the cofactor needed for TRANSALDOLASE?
NONE
how does TRANSALDOLASE work?
contains and active site LYSINE...forms a SCHIFF BASE INTERMEDIATE
what is the product after TRANSALDOLASE reaction?
Fructose-6-Phosphate
2 big reasons cells need NADPH
1) Synthesis
2) GSSG reaction
oxidative branch of Pentose Phosphate Pathway:
converts NADP+ to NADPH
non-oxidative branch of Pentose Phosphate Pathway:
converts Ribulose 5 Phosphate to glycolytic intermediates so that the carbons are not wasted
What happens when NADP+ accumulates?
Glucose 6 Phosphate Dehydrogenase acts on it and makes NADPH
what types of cells would use Pentose Phosphate Pathway to make nucleotides out of Ribose 5 Phosphate?
newborns, tumor cells, heart cells after MI
how do cells make Ribose 5 Phosphate?
uses reversible non-oxidative branch to convert Fructose 6 Phosphate to Ribose 5 Phosphate
which type of cells would reverse the non-oxidative part of Pentose Phosphate Pathway?
those with little oxidative stress (don't need NADPH) and little biosynthetic activity...any cell that hasn't accumulated NADP+
most comon enzyme abnormalty of PP pathway in the clinical setting?
Glucose 6 Phosphate Dehydrogenase Deficiency
what type of inheritance does Glucose 6 Phosphate Dehydrogenase display?
X linked....affects mosly males
what is the clinical presentation of Glucose 6 Phosphate Dehydrogenase?
Hemolytic Anemia....RBC cannot repair themselves and just make more G6P....very sensitive to deficiencies where enzymes are unstable
what can cause the recognition of Glucose 6 Phosphate Dehydrogenase Deficiency?
Oxidative Stress
How do drugs induce the moderate disorder of Glucose 6 Phosphate Dehydrogenase disorder?
drugs that oxidize GSH to GSSG....NADPH is needed to reduce back to GSH
Three drugs that can cause oxidative stress and Glucose 6 Phosphate Dehydrogenase disorder to show up
Antibiotics
Antimalarials
Antipyretics
where is Glucose 6 Phosphate Dehydrogenase deficiency common?
African
Chineese
Medeterranian
what is the evolutionary hold of the Glucose 6 Phosphate Dehyrdogenase deficiency?
provides resistance to malaria....RBCs in which malaria cannot survive