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Flashcards in PPS Deck (32):
1

aliases of PPS

-hexose monophosphate shunt
-the phosphogluconate pathway

2

why is it called a shunt

-you start with glycolytic intermediates and can end with glycolytic intermediates depending on what you are using the shunt for

3

two important products of PPF and why they are important

-ribose-5-P: is needed for nucleotide synthesis
-NADPH: is needed to reduce glutathione (detox), to sythesize fatty acids, NO, and steroids/sterols (cholesterol), to detoxify drugs (cytochrome P450 monoocygenase), and as part of the respiratory burst

4

where is this type of metabolism used often

-5 to 10% of liver metabolism
-more in adipocytes

5

concentrations of NADPH, NADP, NAD, and NADH

-NADPH>>NADP
-NAD>>NADH
-this keeps the balance between oxidized and reduced cofactors balanced within the cell

6

during the non oxidative phase, what is intervonverted

-pentose sugars

7

transketolase transfers what using what
-makes

-2 C's
-using thiamine
-makes G3P and sedoheptulose from xylose and ribose-5-P

8

thiamine deficiency causes

-wernicke-korsakoff
-beri-beri

9

transaldolase transfers

-3 C's
-makes erythrose 4 P and F6P from G3P and sedoheptulose

10

overall reaction of number of sugar phosphates in the non-oxidative portion of PPS

-3 pentose phosphates to 1 triose phosphate and 2 hexose phosphates

11

when you need approximately equal amounts of NADPH and ribose5P, how do you run the pathway

-run the oxidative portion and then convert ribulose5P to ribose5P

12

when you need more ribose than you do NADPH, how do you run the pathway?

-use F6P to enter the pathway instead of G6P, this skips the oxidative portion of the reaction
-convert F6P or G3P directly to ribose-5-P to be used for nucleotide synthesis

13

when you need way more NADPH then ribose

-run the oxidative portion of the reaction the convert ribose5P into glycolytic intermediates which can then be interconverted back to G6P and the oxidative reaction can be ran again
-this is essentially creating one CO2 for every carbon in G6P

14

when you need just a little bit more NADPH than ribose, how do you run the pathway?

-run the oxidative portion then convert ribose into glycolytic intermediates which are then ran through glycolysis to create ATP

15

regulation of PPS via G6PDH

-this is the first committed step in the reaction and is rate limiting
-G6PDH is inducible by insulin
-allosteric feedback inhibited by NADPH (NADPH is a product which will inhibit G6PDH)

16

coenzyme to G6PDH

-NADP+
-this reaction is inhibited by the product NADPH

17

which enzyme defect is a bigger deal: G6PDH or 6-phosphogluconate DH?

-G6PDH is the rate limiting enzyme, so a problem with this will drastically throw off the rate and regulation of the pathway
-a problem with 6-phosphogluconate is not that big of a deal because it isn't controlling the rate, it is just taking what it can get from G6PDH and converting it into ribulose 5 P

18

physiological use for free radicals

-NADPH oxidase is produced by neutrophils and used to make free radicals in order to kill pathogens
-a defect in this process leads to chronic granulomatous disease (skin abscesses)

19

free radical injury is thought to be a contributor to many disease states, such as

-atherogenesis
-ischemia/repeerfusion injury
-alcoholism
-neurodegenerative disease
-acute renal failure
-emphysema

20

enzyme to protect us against superoxides

-superoxide dismutase
-creates hydrogen peroxide from superoxide

21

how does glutathione detoxify peroxides and its cycle

-it is an oxygen acceptor, upon its oxidation, hydrogen peroxide is converted to water by GSH peroxidase (dietary selenium is required)
-once glutathione is in an oxidized state, NADPH is used by GSSG reductase to reduce glutathione to its original state so it can convert another hydrogen peroxide molecule

22

GSH peroxidase
-subtrates and products

-substrate: reduced glutathione and hydrogen peroxide
-products: oxidized glutathione and water

23

GSSG reductase
-substrates and products

-substrates: oxidized glutathione and NADPH
-products: reduced glutathione and NADP+

24

where does the NADPH for reduction of glutathione come from

the first step in PPS, regulated by G6PDH

25

what is responsible for maintaining the cellular environment in a reduced state and why is this important

-glutathione
-disulfide bonds in proteins stay reduced

26

superoxide dismutase reaction

substrate: superoxide and 2 molecular H+
-product: hydrogen peroxide and molecular oxygen

27

what are heinz bodies?

-form in RBC's when cells are exposed to oxidizing agents
-this causes a precipitation of Hb due to oxidation of cystein resiues which form disulfide bonds

28

G6PDH deficiency can cause

-formation of Heinz bodies and anemia

29

signs of G6PDH deficiency

-dark urine: due to hemolysis causing excretion of hemoglobin
-low number of RBC and low Hb: result of high rate of hemolysis
-elevated bilirubin: metabolic product of heme
-increased reticulocytes in circulation (reticulocytosis)

30

why is G6PDH deficiency so common in some areas?

-this is seen in areas like africa that are hot and wet
-causes fragility of the RBC which disrupts the life cycle of malaria
-confers resistance to the disease

31

some drugs that can cause hemolytic anemia

-sulfanomides
-aspirin, NSAIDs
-quinadine and quinine
-napthylene
-fava beans

32

why are RBC's particularly sensitive to a G6PDH deficiency?

-other cells have an alternative pathway that utilizes malate dehydrogenase to make pyruvate and NADPH from malate and NADP+