pentose phosphate pathway

Question 1

2 functions of PPP

Answer 1

• generate NADPH

- provide pentoses for RNA and DNA synthesis

Question 2

another name for PPP

Answer 2

hexose monophosphate shunt

Question 3

where does PPP take place?

Answer 3

cytosol

Question 4

what regulates PPP?

Answer 4

demand for NADPH

Question 5

what is the first substrate in PPP?

Answer 5

glucose-6-P

Question 6

what are the fates of glucose-6-P (3+)

Answer 6

• glycogen synthesis
• glycolysis
• PPP
• “others”

Question 7

rate limiting enzyme in PPP

Answer 7

glucose-6-P dehydrogenase

Question 8

which enzyme is responsible for opening the ring structure?

Answer 8

lactonase

Question 9

what converts ribulose-5-P to ribose-5-P?

Answer 9

isomerase

converts ketose to aldose

Question 10

what does epimerase do?

Answer 10

changes the configuration at one of the epimeric carbons (moves OH to the opposite side)

Question 11

what type of cells will need high PPP activity for the purpose of generating pentoses?

Answer 11

rapidly dividing cells

Question 12

what can cells do if they need to run PPP for NADPH but they don’t need pentoses at the moment?

Answer 12

can convert pentoses into glyceraldehyde-3-P and fructose-6-P that can be fed into glycolysis

Question 13

what is the cofactor required by the first step/third step in pentose conversion?

Answer 13

TPP= cofactor for transketolase

Question 14

what is the oxidative phase of PPP?

Answer 14

generation of NADPH

Question 15

what is the non-oxidative phase of PPP?

Answer 15

pentose conversions when pentoses are in excess

Question 16

what occurs when the need for ribose-5-P is not met by the oxidative phase of PPP?

Answer 16

non-oxidative phase runs in reverse: glyceraldehyde-3-P + fructose-6-P = ribose-5-P

Question 17

wernicke-korsakoff syndrome

Answer 17

thiamine deficiency

sx= apathy, memory loss, rhythmical eye mmts

Question 18

testing for RBC transketolyase activity

Answer 18

measure transketolase activity in hemolyzed whole blood, then add thiamine, if there is over 25% increase in activity after addition = thiamine deficiency

Question 19

differentiate between NADH and NADPH

Answer 19

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

Question 20

where is the highest concentration of glucose-6-p dehydrogenase found? why?

Answer 20

neutrophils/other phagocytes because they use NADPH to generate superoxide radical (O2-) with NADPH oxidase

Question 21

why is glucose-6-P dehydrogenase important to RBCs?

Answer 21

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)

Question 22

what occurs in RBCs with G6PD?

Answer 22

inability to form NADPH = reduced ability to regenerate GSH = reduced ability to deal with hydrogen peroxide = cell lysis/hemolytic anemia secondary to oxidative stress

Question 23

what are heinz bodies?

Answer 23

inclusions in RBCs composed of denatured hemoglobin (met-hgb), seen with G6PD

Question 24

what is the m/c inborn error of metabolism?

Answer 24

G6PD

Question 25

drugs that cause oxidative stress

Answer 25

anti-malarials, sulfa

Question 26

foods that cause oxidative stress

Answer 26

fava beans

Question 27

inheritance pattern of G6PD

Answer 27

X-linked

Question 28

what is meant by “balanced polymorphism”?

Answer 28

G6PD conveys reduction in mortality from malaria = why is is still seen

Question 29

which cells are most vulnerable to G6PD?

Answer 29

RBCs bc other cells have alternative ways of generating NADPH

Question 30

what is another way that cells, other than RBCs, generate NADPH?

Answer 30

malic enzyme= acts on cytosolic form of malate to yield NADPH, Pyruvate and CO2