Pentose phosphate pathway Flashcards by Holly Deere

what is the pentose phosphate pathway

completely different pathway of glucose oxidation
aka the hexose monophosephate shunt
oxidation WITHOUT ATP production

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purpose of the pentose phosphate pathway

supplies ribose-5-phosphate for nucelotide and nuceil acid synthesis
supplies reducing power as NADH for synthesis of fat, cholesterol, steroids etc
provides route for excess pentose sugar inthe diet into mainstream metabolism
recycles sugars according to the needs of the cell

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two phases of the PPP

oxidative and non-oxidative

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why doesnt PPP produce ATP

because the NADPH doesn’t go to the mitochondria and ETC

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where does PPP occur

mainly in the cytosol of cells, along with glycolysis

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where are PPP enzymes most plentiful

in tissues with high demand for NADPH for synthesis
rapidly dividing cells which require ribose-5-phosphate for DNA synthesis
in the liver, because the main demand is for FA synthesis

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quantitatively, what is the main demand of PPP

FA synthesis

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PPP in skeletal muscle

very little activity

but because PPP produces ribose-5-phosphate, all tissues are likely to have some activity

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why do mature erythrocytes need the PPP

they require NADH to maintain the cell membrane integrity

- maintains the reduced environment to stop bursting

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which part of PPP is irreversible and produces ribose-5-phosphate and NADPH

oxidative

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steps of the oxidative PPP

G6P converted to 6-phosphgluconate
NADP+ reduced to NAPDH
enzyme: glucose-6-dehydrogenase
6-phosphogluconate dehydrogenase reduces NADP+ and generates beta-keto-acid
beta-keto-acid decarboxylated to keto-pentose-ribulose-5-phosphate
isomerase converts keto-pentose-ribulose-5-phosphate into aldose isomer: riose-5-phosphate

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what controls the oxidate part of PPP

rate limiting step: oxidation of G6P to 6-phosphogluconolactone, by enzyme glucose-6-dehydrogenase

rate of reaction is tightly coupled to [NAD+] which governs the allocation of G6P to PPP instead of glycolysis

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non oxidative part of PPP

Interconverts sugars according to needs of cells

- involves transaldose and transketolases

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what do transaldose and transketolase do in the non-oxidative part of PPP

detach C3 and C2 respectively from ketose sugar phosphate, and transfer them other aldose sugars

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what is the thiamin (B1) pyrophosphate-dependent enzyme

transketolase (like in the link reaction)

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when do tissues demand high NADPH

during fat synthesis

production of NADPH for fat synthesis also results in increased ribose-5-phosphate
there might be more R5P than cell needs for nucleotide synthesis

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when do tissues demand high R5P

rapidly dividing cells that arent synthesizing fat, have high requirement for R5P but not NADPH

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how do requirements for NADPH and R5P alter

vary with different tissue demands
the demand for R5P and NADPH can be equal, or weighted to one more than the other

production is controlled by the non-oxidatve part of the pathway

what controls balance of NADPH and R5P production

non-oxidative part of PPP

Oxidative balance equation

G6P + 2NADP+ + H2O –> R5P + 2NADPH + 2H+ + CO2

when is the non-oxidative part of PPP not needed

when the oxidative part is balanced

When does conversion of R5P to X5P occur

when the liver needs 2NADPH but does not need the R5P of the balance equation
- phosphophentose isomerase and epimerase

X5P

xylulose 5 phosphate

what else does R5P get converted to when in excess

R5P to glyceraldehyde3P and F6P

these can enter glycolysis or gluconeogenesis
F6P can also be converted to G6P and reenter PPP

occurs by 3 reactions using transketolase, transaldolase and transketolase again

conversion of surplus R5P into G6P: when and how

if non dividing cell requires more NADPH than R5P the non-oxidative part recycles excess into G6P 6 R5P -> 5 G6P + Pi

conversion of R5P into glyceraldehyde-3-phosphate: why

G3P can then be converted to G6P by gluconeogenesis reactions

6 C5 sugars are converted to

5 x G6P (3 R5P and 3 XYP

conversion of G6P into R5P without NADPH generation : summary

if a cell needs R5B for nuceotide synthesis but has little demand for NADPH: G6P + ATP -> 6R5P + ADP + Pi - where R5P is required and NADH isnt - oxidative part of PPP doesn't operate - glycolytic intermediates are converted to R5P by transketolase and transaldolase enzymes

steps of conversion of G6P into R5P without NADPH generation

- G6P is converted by glycolytic pathway partly in F6P an partly into glyceraldehyde3P = C3 and C6 products - reversal of the these steps produces X5P which is isomerised to R5P

why is the PPP important for erythrocyte

- mature erythrocytes do not divide - no need for R5P for nuclei synthesis or fat synthesis bc they derive energy from glycolysis BUT they need a supply of NADPH to protect cell membrane from oxidative damage

Protective effect of NADPH on erythrocytes

- RBC membrane is subject to attack by H2O2 - H2O2 needs to be detoxified - 2 reduced GSH attack H2O2 to make water and the GSH become oxidised to GSSG - GSSG is useless so FAD re-reduces to farm GSH again - NADPH is needed to activate the GSSG to GSH

Main function of glutathione

to maintain reducing environemnt in cells by virtue of its -SH group (thiol) AHA GSH

why are RBC susceptible to oxidative damage

- high O2 content in cell gives rise to harmfel ree radicals or ROS - RBC depend on GSH for integrity - GSH reduces ferrihaemoglobin to ferrous form - GHS destroys H2O2 - GSH regenerates reduction environemnt using NADPH

why does RBC depend on GSH

- GSH reduces ferrihaemoglobin to ferrous form - GHS destroys H2O2 - GSH regenerates reduction environemnt using NADPH therefore continuous supply of NADPH is also key

GSH

glutathione

what is the only way of generating NADPH and GSH inthe cell

PPP and hence vital for RBC

G6P dehydrogenase deficiency

most common human enzyme disorder - X-linked hereditary disorder so most asymptopic - symptopic patients usally male - more than 400mil worldwide are G6PD deficient, mostly in Africa, middle East and south Asia

what happens to people with G6PD

they can be completely OK until ertythrocyte is challenged with oxidation = haemolytic anaemia

triggers for haemolytics anaemia

- favism - infection - oxidant drugs

favism

ingestion of fava beans - some forms of G6PD, particulary mediterraneon varient, are particulary susceptible to favism - fava beans contain alkaloids such as vicine which are potent oxidants

infection triggering haemolytic anaemia

inflammatory response to infection can lead to generationof oxidatns such as fre radicals, which enter E and cause haemolysis

oxidant drugs triggering haemolytic anaemia

antimalaria drugs; chloroquine can be harmful - indivuduals should be tested for G6PD before being prescribed these - sulphonamides, sulfa antiobiotics and analgesics should also be avoided

sidelight of G6PD

selective advantage in areas where lethal type of malaria is endemic possible reasons: - parasite had requirement for products of PPP - AND/OR extra stress by parasite causes the deficient RBC host to lyase before parasite completes development (doesnt live usual 120 days) similar to sickcell - potentially lethal disease that provides survival advantage against an even more lethal disease