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Flashcards in PPS Deck (32)
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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

-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

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


thiamine deficiency causes



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

-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

-ischemia/repeerfusion injury
-neurodegenerative disease
-acute renal failure


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

-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