Exam 2 Lecture 22 PP Pathway Flashcards
if we have G6P and the enzyme G6P isomerase is working on it, this means the pathway desired is _?
glycolysis or gluconeogenesis
if we have G6P and the enzyme phosphoglucomutase is working on it, this means that the pathway desired is _?
store or breakdown glucose from/to glycogen
the _ phase makes NADPH
oxidative phase
what is the 1st of the 3 reactions for making NADPH
glucose-6-phosphate dehydrogenase oxidizes G6P to form a lactone as well as reduces NADP+ to form NADPH
what is the 2nd of the 3 reactions for making NADPH
lactonase (a hydrolase) opens the ring by adding water
what is the 3rd of the 3 reactions for making NADPH
6-Phosphogluconate dehydrogenase catalyzes the oxidative decarboxylation of 6-phosphogluconate to form ribose 5-phosphate and reduces NADP+ to form NADPH
what is the rate limiting step of phase 1 of PPP
glucose 6-phosphate dehydrogenase
NAD+ is primarily used for
catabolism (oxidative pathway) uses dehydrogenases; e- transport and OxPhos
NADP+ is primarily used for
anabolism (reductive pathway) uses reductases; trying to build NADP+ up for PPP
what are the 2 reasons we need NADPH?
- biosynthetic; synthesis of monomers
2. reducing power of NADPH for detoxification; primarily glutathione (RBCs)
what are some biosynthesis of monomers that require NADPH?
- FA syn
- Cholesterol syn
- Neurotransmitter syn
- Nucleotide syn
what are the tissues with active PPPs?
- adrenal gland, testes, ovary (steroid syn)
- liver, adipose tissue, mammary gland (FA syn)
- liver also cholesterol syn
in the tripeptide glutathione, the gamma linkage is unique as it links the _
oxygen in the side chain of glutamate instead the oxygen in the backbone
what are the 3 options for glutathione redox chemistry?
- interactions with proteins (no enzyme needed) ie disulfide bonds
- inactivation of peroxides (enzyme glutathione peroxidase) ie ROS
- regeneration of reduced glutathione (uses NADPH to make NADP+ = substrate for PPP)
what happens when NADPH is under produced?
G6-phopsphate dehydrogenase deficiency = death of RBCs
what are they types of erythrocyte diseases?
issues with Hb, membrane/cytoskeleton defects, and metabolic errors
Fe in heme must be _ to bind O2
reduced
what other proteins can make NADPH?
- isocitrate dehydrogenase (3 isozymes)
- malic enzyme (ME1) interconverts malate and pyruvate in the cytoplasm
excessive amount of conjugated bilirubin causes _
jaundice
most severe effect of G6PDD is blood is ‘normal’ but liver cannot
conjugate bilirubin
the monomer form of G6PD is active or inactive?
inactive
what are the 2 active forms of G6PD
dimer and tetramer
conditions favoring the inactive form of G6PD
high amounts of NADPH, G6P, pH
conditions favoring the active dimer form of G6PD
high ionic strength (salt) and pH > 8
conditions favoring the active tetramer form of G6PD
high NADP+ and low pH (<6)
T/F: NADP+ is both a substrate and a coenzyme
true
the importance of G6PD and ATM
Hsp27 interacts with G6PD and promotes G6PD dimerization ie promotes activation
what are the activators for G6PD regulation?
- dimerization
- TFs for antioxidant genes
- Cell cycle and synthesis activators
- insulin
what are the inhibitors for G6PD regulation?
- phosphorylation
- apoptosis-signaling proteins
_ is direct correlation to activating G6PD
insulin
increase in _ is not a direct correlation to activating G6PD
increase in EXTRACELLULAR GLUCOSE can either increase or decrease G6PD
the _ phase shuffles carbons (4 shuffles)
nonoxidative
shuffle 1: 1st of the 2 enzymes that could be used;
ribose 5-phosphate isomerase shuffles a
moves a hydrogen converts ribulose-5-phosphate into ribose-5-phosphate
shuffle 1: 2nd of the 2 enzymes that could be used;
ribulose-5-phosphate epimerase shuffles a
moves a hydroxyl converts ribulose-5-phosphate to xylulose-5-phosphate
shuffle 2:
transketolase transfer 2-C from _ leaving behind glyceraldehyde-3-phosphate (3-C)
xylulose-5-phosphate (5-C)
TPP coenzyme stabilizes
transition state of transketolase
shuffle 3:
transaldolase transfers _ units
3-C
transaldoase is _ enzyme classification and whose transition state stabilized by
transaldolase is hydrolase enzyme and stabilized by Lysine side chain
shuffle 4:
regenerates _ via gluconeogenesis pathway
G6P; uses F6P and GAP
if you need NADPH from PPP, then you need
anabolic ie biosynthesis. Uses full PPP cycle and primary product is NADPH
if you need energy from PPP, then you need
glycolysis primary products are F6P + GAP ie skipping the last shuttle of PPP so can have glycolysis
if you need nucleotides from PPP, then you need
- option 1: nonoxidative phase in reverse
- option 2: oxidative phase only; primary products are ribose 5-phosphate + NADPH
