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Biochemistry MBS > PPS > Flashcards

PPS Flashcards

1
Q

aliases of PPS

A
  • hexose monophosphate shunt

- the phosphogluconate pathway

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2
Q

why is it called a shunt

A

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

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3
Q

two important products of PPF and why they are important

A
  • 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
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4
Q

where is this type of metabolism used often

A
  • 5 to 10% of liver metabolism

- more in adipocytes

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5
Q

concentrations of NADPH, NADP, NAD, and NADH

A
  • NADPH»NADP
  • NAD»NADH
  • this keeps the balance between oxidized and reduced cofactors balanced within the cell
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6
Q

during the non oxidative phase, what is intervonverted

A

-pentose sugars

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7
Q

transketolase transfers what using what

-makes

A
  • 2 C’s
  • using thiamine
  • makes G3P and sedoheptulose from xylose and ribose-5-P
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8
Q

thiamine deficiency causes

A
  • wernicke-korsakoff

- beri-beri

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9
Q

transaldolase transfers

A
  • 3 C’s

- makes erythrose 4 P and F6P from G3P and sedoheptulose

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10
Q

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

A

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

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11
Q

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

A

-run the oxidative portion and then convert ribulose5P to ribose5P

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12
Q

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

A
  • 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
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13
Q

when you need way more NADPH then ribose

A
  • 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
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14
Q

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

A

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

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15
Q

regulation of PPS via G6PDH

A
  • 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)
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16
Q

coenzyme to G6PDH

A
  • NADP+

- this reaction is inhibited by the product NADPH

17
Q

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

A
  • 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
Q

physiological use for free radicals

A
  • 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
Q

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

A
  • atherogenesis
  • ischemia/repeerfusion injury
  • alcoholism
  • neurodegenerative disease
  • acute renal failure
  • emphysema
20
Q

enzyme to protect us against superoxides

A
  • superoxide dismutase

- creates hydrogen peroxide from superoxide

21
Q

how does glutathione detoxify peroxides and its cycle

A
  • 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
Q

GSH peroxidase

-subtrates and products

A
  • substrate: reduced glutathione and hydrogen peroxide

- products: oxidized glutathione and water

23
Q

GSSG reductase

-substrates and products

A
  • substrates: oxidized glutathione and NADPH

- products: reduced glutathione and NADP+

24
Q

where does the NADPH for reduction of glutathione come from

A

the first step in PPS, regulated by G6PDH

25
Q

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

A
  • glutathione

- disulfide bonds in proteins stay reduced

26
Q

superoxide dismutase reaction

A

substrate: superoxide and 2 molecular H+

- product: hydrogen peroxide and molecular oxygen

27
Q

what are heinz bodies?

A
  • 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
Q

G6PDH deficiency can cause

A

-formation of Heinz bodies and anemia

29
Q

signs of G6PDH deficiency

A
  • 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
Q

why is G6PDH deficiency so common in some areas?

A
  • 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
Q

some drugs that can cause hemolytic anemia

A
  • sulfanomides
  • aspirin, NSAIDs
  • quinadine and quinine
  • napthylene
  • fava beans
32
Q

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

A

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

Biochemistry MBS (36 decks)

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