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IBMS > The pentose phosphate pathway > Flashcards

The pentose phosphate pathway Flashcards

1
Q

Name 4 reasons the PPP is important?

A
  • oxidise glucose to created NADPH
  • PPP is a pathway to produce pentose sugars which are incorporated to CoA DNA,RNA NADH, FAD and ATP
  • Route to breakdown pentose sugars obtained form the diet
  • PPP enables the anabolism and catabolism of 7 and 4 carbon containing sugars
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2
Q

What is the importance of NADPH

A
  • needed for reductive biosynthesis
  • counter damage effect of free radicals
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3
Q

what is important in the production of FA

A
  • large amount of NADPH
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4
Q

How many NADPH is needed in fatty acid biosynthesis when producing palmitate

A

14 NADPH

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5
Q

what is the difference between NADH and NADPH

A
  • Phosphate which allows binding into two sites on NADPH
  • phosphate changes it shape to bind to different sets of enzymes
  • NADPH operates with enzymes THAT CATALYSE ANABOLIC REACTIONS, suPPLYIGN HIGH ENERGY ELECTRONS NEEDED TO SYNTHESISE ENERGY Rich biological molecules
  • NADH - has a role as an intermediate in the catholic system of reaction that generate STP through he oxidation of food molecules
  • Radio of NAD+ : NADH is kept high
  • ratio of NADP+ to NADPH is kept low
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6
Q

Describe how NADPH is generated in the pyruvate malate cycle

A
  • Getting acetyl CoA into mitochondria to cytosol

-Produces NADPH after citrate is shuttles out of mitochondrial and ATP citrate lyase forming OAA- to malate and to pyruvate to produce NADPH
-For each ACetyl COa transferred from the mitochondria to cystol= 1 NADPH is produced
But we need more

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7
Q

How many stages does the PPP have

A

2 stages
oxidative ( irreversible)
non oxidative (reversible )

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8
Q

where is PPP conducted

A

systole of cell

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9
Q

what does PPP produce

A

NADPH
Ribose 5 phposhate

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10
Q

where does PPP occur (different organs)

A

-Liver
- lactating mamary glands,
-adipose tissue
-adrenal cortex
- Red blood cells

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11
Q

how much percentage is there of G6P due to PPP in the RBC , Brian and heart and traumatic Brain injury?

A
  • RBC= 5%
  • Brain = 7%
  • heart =1%
  • traumatic Brian injury = 15%
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12
Q

how many molecules of NADPH is formed when G6P is oxidised

A

2

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13
Q

Name the 3 step of PPP in odiidaitve phase

A

1- ester formation
2-ring opening
3- decarboxylation

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14
Q

Describe the oxidative phase of PPP

A
  • 1st - ester formation
    dehydrogenation of G6P resulting in transfer of hydride ion and 2 electrons onto NADP+
  • results in production of 1 NADPH and ester intermediate
    ( G6P——- 6 phophsolgucano delta lactone)
    using G6P dehydrogenase

2- ring opening via hydrolysis reaction
6 phopshglucan delta lactose is hydrolysed to 6 phosphglucante using enzyme lactonase

3- decabroxylation - 6 phosphoglucante is oxidised as NADP+ picked up an electron and hydrogen to form ribulose 6 phosphate

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15
Q

what is the net product in these 3 oxidative steps of PP

A

2 NADPH
- loss of one carbon

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16
Q

what does lactonase do

A
  • hydrolase 6 phosphogluono delta lactone to 6 phosphgluconate
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17
Q

what does glucose 6 phosphate dehydrogenase do

A
  • aid in the ester formation step of oxidative phase
  • converts G6P to 6 Phosphoglucono delta lactone
  • reduced 1 NADPH
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18
Q

what does 6 phisphogluconate dehydrogenase do

A
  • aids in decarboxylation
    of 6 phosphogluconate to ribulose 5 phosphate
  • produces NADPH
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19
Q

what doe cells require more of NADPH or ribose 5 phosphate

A

NADPH

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20
Q

why is there a reason for the non oxidative phase

A
  • the intermediates for glycolysis can be produced
  • F6P and GAP
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21
Q

how can F6P and GAP generate NADPH

A

F6P can directly go through the oxidative way by converting to G6P
GAP can go on to form pyruvate , cross into mitochondria , form citrate and be transported out through the pryuavte malate cycle generating more NADPH

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22
Q

Is the non oxidative phase reversible

A

yes

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23
Q

What is involved in the non oxidative phase

A

Ribulose 5 phosphate can do either isomerisation
Ribose 5 phosphate needed for nucleotide synthesis
Or when we need to have lots more NADPH, phosphopentose epimerase cna produce Xylulose 5 phosphate

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24
Q

what non oxidative isomer produces more NADPH

A

Xylulose 6 phosphate

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25
Q

what molecule is beneficial for generating nucleotides

A

ribose-5 - phosphate

26
Q

How can Xylulose 5- posphate and Ribose 5 phosphate generate F6P and GAP for NADPH synthesis

A

If X5P and R5P react using transketolase- this transfers carbon 1 and cabron 2 of X5P forming SH7P, the remaining 3 carbons product GAP
Next the transaldolase catalyses reaction between GAP and SH7P where 3C fragment removed from SH7P and is condensed with GAP to form F6P and E4P
Then the transketolase acts again using E4P and X5P to produce F6P and GAP
Continuing cycle which can produce many substrates for glycolysis pathway
F6P can feedback into this pathway
GAP can form pyruvate and go into the pyruvate malate cycle

27
Q

what does transketolase do and transaldoase

A
  • transketolase is used to reaction X5P with R5P to produce Sedoheptulose 7 phosphate and GAP
    (transfers carbon 1 and carbon 2 of X5P forming SH7P)
  • transolaade catalyses reaction between GAP and S7HP where 3C fragment is removed from SH7D and condensed with GAP to form F6P and E4P
  • Then the transketolase acts again using E4P and X5P to produce F6P and GAP
    Continuing cycle which can produce many substrates for glycolysis pathway
28
Q

How is PPP regulated in the oxidative pathway control

A
  • in the first step
  • driven by ratio of NADPH: NADP+
  • low NADPH , high NADP+ - activates pathway increasing NADPH production
29
Q

How is the non oxidative pathway regulated?

A
  • driven by the need for products R5P and NADPH
  • needs of the cell determine the production of R5P, F6P,GAP
30
Q

what happens if the cell needs lots of NADPH

A

G6P shuttles of PPP where GAP and 2x F6P are produced and feed into the glycolysis pathway
F6P produces more G6P for shunt to continue

31
Q

what will happen if the cells need some NADPH and ATP

A

PPP uses little G6P to produce products which feed into F6P but because we need ATP this isn’t shuttled back to G6P and undergo glycolysis pathways in order to enter citric acid cycle

32
Q

what happens if the cell needs a lot of R5P

A

If we are in need of a lot of ribose 5 phosphate - producing a lot of nucleotides
Glycolysis pathways can produce F6P and GAP and because they are reversible reactions they can cascade back up through the non oxidative apart of our PPP to produce lots of R5P

33
Q

What is ROS

A

reactive oxidative species

34
Q

4

name some highly reactive oxygen containing molecules

A

Superoxide anion radical
- hydroxyl radical
- Inorganic peroxides
- Hydrogen peroxide

35
Q

what is the reactivity due to in ROS

A
  • unpaired electrons
36
Q

what can damage to DNA lead to

A
  • genetic changes
  • cancer
  • protein with long half lives
    -changes associated with aging
  • damage to lipids contribute to atherosclerosis
37
Q

how much percentage of Oxygen coverts to ROS

A

1%

38
Q

what molecule enhances the formation of ROS

A

free iron

39
Q

What does NADPH do in relation to ROS

A

NADPH as a reduction proteins the cells from oxidative damage from Hydrogen peroxide and superoxide radicals

40
Q

what happens during normal detoxification

A

Peroxide is converted to water by reduced glutathione and glutathione peroxidase
- Oxidised glutathione is converted back to its reduced fro by glutathione reductase and NADPH
-As we have our reduced form, we can then continue to breakdown the peroxide
This is dependant on the regeneration of NADPH- of we don’t have NADPH we can’t regenerate reduced glutathione
We regenerate NADPH using our first step of PPP which required G6P dehydrogenase
Common deficiency in our enzyme and those people who have this enzyme deficiency are unable to produce NADPH therefore detoxification by peroxide in inhibited

41
Q

what enzyme is a common deficiency

A

Glucose 6 - phosphate dehydrogenase

42
Q

what symptoms doe the G6PD deficient individuals carry

A

asymptomatic

43
Q

what ingredients are found in falafel’s

A

fava beans
intern contain ‘ divicine’

44
Q

falafel ingredient

what does the divicine ingredient do

A
  • when ingested the beans lyse releasing free haemoglobin and the toxic ingredient
  • normal detoxification would convert hydrogen peroxide to water but he production of NADPH is diminished in G6PD deficiency individuals
  • cellular damage would result
45
Q

falafel

when is G6PD deficiency a problem

A
  • massive oxidative stress caused falafels herbicides and drugs
46
Q

how is divicine good for individuals

A
  • acts as a antimalarial and ingestion of lava beans may protect against malaria with normal G6PD activity
47
Q

what frequency in AFRICA, Middle East and South east Asia are G6PD deficient

A

25%

  • malaria is most prevalent
48
Q

what happens when parasite is inhibited by G6PD deficient erythrocytes

A
  • sensitive to oxidative damage and high level of oxidative stress tolerable to a G6PD human host killing parasite
49
Q

What stimulates PPP overall?

A

Anything that consumes ribose 5 phosphate

50
Q

Is NADPH an electron donor or acceptor?

A

Donor

51
Q

Dehydrogenation of what substance occurs in the first step of PPP?

A

Glucose 6 phosphate

52
Q

Hydrolysis of what substance occurs in the second step of PPP?

A

6 phosphate gluconate alpha lactone (6-phosphogluconolactone)

53
Q

What occurs in the third step of oxidative decarboxylation in PPP?

A

Occurs to 6-P gluconate to yield ribulose 5 phosphate

54
Q

What occurs in the fourth isomeric action step in PPP?

A

Ribulose 5 phosphate to ribose 5 phosphate

55
Q

What effect does NADPH have on glucose 6 phosphate dehydrogenase?

A

Inhibition (because it’s a product)

56
Q

What is an extra product of the third step of PPP, besides the ribulose 5 phosphate and NADPH?

A

CO2 (carbon dioxide)

57
Q

n which two steps of PPP is NADPH made?

A

Step one - dehydrogenation & step three - oxidative decarboxylation

58
Q

If there is low energy in the cell, where are the intermediates of PPP, such as G3P, going to go?

A

Glycolysis (to make energy)

59
Q

What do the fat synthesis and cholesterol pathways use up that eventually stimulates PPP?

A

NADPH

60
Q

What enzymes make up the reversible reactions of PPP that provide linkages with this pathway and glycolysis?

A

Transketolases and transaldolases

61
Q
A

IBMS (6 decks)

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