pentose phosphate pathway Flashcards
2 functions of PPP
- generate NADPH
- provide pentoses for RNA and DNA synthesis
another name for PPP
hexose monophosphate shunt
where does PPP take place?
cytosol
what regulates PPP?
demand for NADPH
what is the first substrate in PPP?
glucose-6-P
what are the fates of glucose-6-P (3+)
- glycogen synthesis
- glycolysis
- PPP
- “others”
rate limiting enzyme in PPP
glucose-6-P dehydrogenase
which enzyme is responsible for opening the ring structure?
lactonase
what converts ribulose-5-P to ribose-5-P?
isomerase
converts ketose to aldose
what does epimerase do?
changes the configuration at one of the epimeric carbons (moves OH to the opposite side)
what type of cells will need high PPP activity for the purpose of generating pentoses?
rapidly dividing cells
what can cells do if they need to run PPP for NADPH but they don’t need pentoses at the moment?
can convert pentoses into glyceraldehyde-3-P and fructose-6-P that can be fed into glycolysis
what is the cofactor required by the first step/third step in pentose conversion?
TPP= cofactor for transketolase
what is the oxidative phase of PPP?
generation of NADPH
what is the non-oxidative phase of PPP?
pentose conversions when pentoses are in excess
what occurs when the need for ribose-5-P is not met by the oxidative phase of PPP?
non-oxidative phase runs in reverse: glyceraldehyde-3-P + fructose-6-P = ribose-5-P
wernicke-korsakoff syndrome
thiamine deficiency
sx= apathy, memory loss, rhythmical eye mmts
testing for RBC transketolyase activity
measure transketolase activity in hemolyzed whole blood, then add thiamine, if there is over 25% increase in activity after addition = thiamine deficiency
differentiate between NADH and NADPH
NADPH has a phosphate attached to OH, hydrogens cannot be transferred between NADH and NADPH, NADPH is used in anabolic pathways, separating NADH and NADPH allows for better regulation
where is the highest concentration of glucose-6-p dehydrogenase found? why?
neutrophils/other phagocytes because they use NADPH to generate superoxide radical (O2-) with NADPH oxidase
why is glucose-6-P dehydrogenase important to RBCs?
RBCs use glucose-6-P dehydrogenase (via PPP) to synthesize NADPH, RBCs need NADPH so that they can reform GSH with glutathione reductase (GSH then detoxified ROS via glutathione peroxidase)
what occurs in RBCs with G6PD?
inability to form NADPH = reduced ability to regenerate GSH = reduced ability to deal with hydrogen peroxide = cell lysis/hemolytic anemia secondary to oxidative stress
what are heinz bodies?
inclusions in RBCs composed of denatured hemoglobin (met-hgb), seen with G6PD
what is the m/c inborn error of metabolism?
G6PD
drugs that cause oxidative stress
anti-malarials, sulfa
foods that cause oxidative stress
fava beans
inheritance pattern of G6PD
X-linked
what is meant by “balanced polymorphism”?
G6PD conveys reduction in mortality from malaria = why is is still seen
which cells are most vulnerable to G6PD?
RBCs bc other cells have alternative ways of generating NADPH
what is another way that cells, other than RBCs, generate NADPH?
malic enzyme= acts on cytosolic form of malate to yield NADPH, Pyruvate and CO2
