PPS Flashcards
aliases of PPS
- hexose monophosphate shunt
- the phosphogluconate pathway
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
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
where is this type of metabolism used often
- 5 to 10% of liver metabolism
- more in adipocytes
concentrations of NADPH, NADP, NAD, and NADH
- NADPH»NADP
- NAD»NADH
- this keeps the balance between oxidized and reduced cofactors balanced within the cell
during the non oxidative phase, what is intervonverted
-pentose sugars
transketolase transfers what using what
-makes
- 2 C’s
- using thiamine
- makes G3P and sedoheptulose from xylose and ribose-5-P
thiamine deficiency causes
- wernicke-korsakoff
- beri-beri
transaldolase transfers
- 3 C’s
- makes erythrose 4 P and F6P from G3P and sedoheptulose
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
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
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
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
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
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)
coenzyme to G6PDH
- NADP+
- this reaction is inhibited by the product NADPH
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
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)
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
enzyme to protect us against superoxides
- superoxide dismutase
- creates hydrogen peroxide from superoxide
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
GSH peroxidase
-subtrates and products
- substrate: reduced glutathione and hydrogen peroxide
- products: oxidized glutathione and water
GSSG reductase
-substrates and products
- substrates: oxidized glutathione and NADPH
- products: reduced glutathione and NADP+
where does the NADPH for reduction of glutathione come from
the first step in PPS, regulated by G6PDH
what is responsible for maintaining the cellular environment in a reduced state and why is this important
- glutathione
- disulfide bonds in proteins stay reduced
superoxide dismutase reaction
substrate: superoxide and 2 molecular H+
- product: hydrogen peroxide and molecular oxygen
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
G6PDH deficiency can cause
-formation of Heinz bodies and anemia
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)
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
some drugs that can cause hemolytic anemia
- sulfanomides
- aspirin, NSAIDs
- quinadine and quinine
- napthylene
- fava beans
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+
