PPS

Question 1

aliases of PPS

Answer 1

• hexose monophosphate shunt

- the phosphogluconate pathway

Question 2

why is it called a shunt

Answer 2

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

Question 3

two important products of PPF and why they are important

Answer 3

• 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

Question 4

where is this type of metabolism used often

Answer 4

• 5 to 10% of liver metabolism

- more in adipocytes

Question 5

concentrations of NADPH, NADP, NAD, and NADH

Answer 5

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

Question 6

during the non oxidative phase, what is intervonverted

Answer 6

-pentose sugars

Question 7

transketolase transfers what using what

-makes

Answer 7

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

Question 8

thiamine deficiency causes

Answer 8

• wernicke-korsakoff

- beri-beri

Question 9

transaldolase transfers

Answer 9

• 3 C’s

- makes erythrose 4 P and F6P from G3P and sedoheptulose

Question 10

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

Answer 10

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

Question 11

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

Answer 11

-run the oxidative portion and then convert ribulose5P to ribose5P

Question 12

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

Answer 12

• 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

Question 13

when you need way more NADPH then ribose

Answer 13

• 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

Question 14

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

Answer 14

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

Question 15

regulation of PPS via G6PDH

Answer 15

• 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)

Question 16

coenzyme to G6PDH

Answer 16

• NADP+

- this reaction is inhibited by the product NADPH

Question 17

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

Answer 17

• 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

Question 18

physiological use for free radicals

Answer 18

• 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)

Question 19

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

Answer 19

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

Question 20

enzyme to protect us against superoxides

Answer 20

• superoxide dismutase

- creates hydrogen peroxide from superoxide

Question 21

how does glutathione detoxify peroxides and its cycle

Answer 21

• 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

Question 22

GSH peroxidase

-subtrates and products

Answer 22

• substrate: reduced glutathione and hydrogen peroxide

- products: oxidized glutathione and water

Question 23

GSSG reductase

-substrates and products

Answer 23

• substrates: oxidized glutathione and NADPH

- products: reduced glutathione and NADP+

Question 24

where does the NADPH for reduction of glutathione come from

Answer 24

the first step in PPS, regulated by G6PDH

Question 25

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

Answer 25

- glutathione | - disulfide bonds in proteins stay reduced

Question 26

superoxide dismutase reaction

Answer 26

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

Question 27

what are heinz bodies?

Answer 27

- 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

Question 28

G6PDH deficiency can cause

Answer 28

-formation of Heinz bodies and anemia

Question 29

signs of G6PDH deficiency

Answer 29

- 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)

Question 30

why is G6PDH deficiency so common in some areas?

Answer 30

- 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

Question 31

some drugs that can cause hemolytic anemia

Answer 31

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

Question 32

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

Answer 32

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