PPP Flashcards
What are major functions of PPP?
- formation of NADPH for synthesis of FAs and steroids and maintaining reduced glutathione for antioxidant activity
- synthesis of RIBOSE for nucleotide, nuclei acid formation
what are the main hexoses absorbed from GI tract?
glucose, fructose, galactose
What will fructose and galactose be converted into in the liver?
Glucose
glucose-6-phosphate dehydrogenase deficiency
Acute hemolysis of RBC = hemolytic anemia
In the PPP, what is used as hydrogen acceptor IOT achieve oxidation?
NADP+
What enzyme catalyzes the dehydrogenation of G6P to 6-phosphogluconalactone?
G6P dehydrogenase
What enzyme hydrolyzes 6-phosphogluconalactone?
gluconalactone hydrolase
What catalyzes the 2nd oxidative step of PPP?
6-phosphogluconate dehydrogenase
What enzyme catalyzes the reduction of cortisone (inactive) to cortisol (active) in liver, NS, & adipose tissue?
11-b-hydroxysteroid dehydrogenase-1
What increases xylulose excretion?
aminopyrine and antipyrine
What can high oral doses of fructose cause?
osmotic diarrhea
What causes hereditary fructose intolerance?
Absence of aldose B
how is glucuronic acid synthesized from glucose?
uronic acid pathway
what is the importance of glucuronic acid?
conjugation & excretion of metabolites & foreign chemicals as glucuronides; largely responsible for elimination of poisonous substances
highly soluble compound that can bind to substances such as hormones, drugs, & toxins to facilitate their transport around body
In PPP, 3 molecules of glucose give rise to ?
3 molecules of CO2
3 5-carbon sugars
2 molecules of _______ will regenerate G6P
glyceraldehyde-3-phosphate
reactions of PPP occur in?
cytosol
what 2 phases does PPP go through?
- irreversible oxidative phase
- reversible nonoxidative phase
What happens in the first phase of PPP?
G6P is dehydrogenated & decarboxylated to form a pentose, ribulose-5-phosphate
what happens in the 2nd phase?
ribulose-5-phosphate is converted back to G6P by a series of rxns involving TRANSKETOLASE and TRANSALDOLASE.
What enzyme catalyzes first oxidative step in PPP? (1st)
glucose-6-phosphate dehydrogenase
(NADP+ used —> NADPH)
(enzyme oxidized G6P to 6-phosphogluconalactone)
What happens after G6P is oxidized to 6-phosphogluconalactone? What enzyme is at work? (2nd)
6-phosphogluconalactone is hydrolyzed to 6-phosphogluconate by the enzyme GLUCONALACTONE HYDROLASE
What happens after 6-phosphogluconalactone is hydrolyzed to 6-phosphogluconate? What enzyme is in play? (3rd)
6-phosphogluconate is decarboxylated to ribulose-5-phosphate
by the enzyme 6-phosphogluconate dehydrogenase.
this is also the 2nd oxidative process in PPP
(NADP+ used –> NADPH)
what are the 2 NADP-dependent enzymes in PPP?
glucose-6-phosphate dehydrogenase
6-phosphogluconate dehydrogenase
In ER, what is hexose-6-phosphate dehydrogenase? what does it do?
- isoenzyme of G6P dehydrogenase
- provides NADPH for hydroxylation rxns and also for 11-B-hydroxysteroid dehydrogenase-1
the non-oxidative phase of PPP generates?
ribose precursors
what happens after decarboxylation to ribulose-5-phosphate?
2 products are made
- ribulose-5-phosphate is converted to the epimer xylulose-5-phosphate (ketopentose) via EPIMERASE
- ribulose-5-phosphate is converted to ribose-5-phosphate (aldopentose) via RIBOSE-5-PHOSPHATE KETOISOMERASE
what is used for nucleotide and nucleic acid synthesis?
ribose-5-phosphate
transfers 2-carbon unit comprising carbons 1 & 2 of a ketose onto aldehyde carbon of an aldose sugar
transketolase
what products are produced when transketolase catalyzes transfer of 2-carbon unit from xylulose 5 phosphate to ribose-5-phosphate?
7-carbon ketose sedoheptulose-7-phosphate
aldose glyceraldehyde-3-phosphate
what happens when the 2 products produced by the transketolase enzyme undergoes TRANSALDOLATION?
transaldolase catalyzes transfer of 3-carbon dihydroxyacetone moiety from ketose sedoheptulose-7-phosphate onto aldose glyceraldehyde-3-phosphate to form
KETOSE FRUCTOSE-6-PHOSPHATE and 4-carbon aldose ERYTHROSE-4-PHOSPHATE
what co-factors are needed by transketolase?
magnesium
thiamin diphosphate (vit B1)
how does the reaction catalyzed by transadolase proceed?
- no co-factor
- rxn proceeds via intermediate formation of Schiff base of dihydroxyacetone to E-group of a lysine residue in enzyme
xylulose-5-phosphate(donor) will react w/ erythrose-4-phospate (acceptor) by donating GLYCOLALDEHYDE to produce
fructose-6-phosphate
GA3P
rxn catalyzed by transketolase
differences b/w PPP and glycolysis
- NADP+ vs NAD+
- production of CO2 vs CO2 not produced
- No ATP generated vs product ATP
how are PPP and glycolysis connected?
xylulose-5-phosphate activates protein phosphatase that DEPHOSPHORYLATES 6-PFK-2/F26Bisphatase bifunctional enzyme, activating GLYCOLYSIS.
X5P also activates protein phosphatase that initiates nuclear translocation & DNA binding of carb response element-binding protein, leading to increased FA synthesis.
PPP is active in what organs or parts of the body?
liver adipose tissue erythrocytes lactating mammary gland adrenal cortex thyroid testis
PPP activity is low in what parts of the body?
skeletal muscle
non-lactating mammary gland
can synthesis of G6P dehydrogenase and 6-phosphogluconate dehydrogenase be induced by insulin?
yes it can in fed state, when lipogenesis increases
why do tissues have to synthesize the ribose they need for nucleotide & nucleic acid synthesis from PPP?
b/c little or no ribose circulates in th bloodstream
an enzyme that contains selenium analog of cysteine (selenocysteine) at active site
glutathione peroxidase
alternative oxidative pathway for glucose that also does not yield ATP like PPP
uronic acid pathway
why are humans unable to synthesize ascorbic acid?
due to absence of L-gluconalactone oxidase
why does fructose undergo more rapid glycolysis in liver than does glucose?
fructose bypasses regulatory step catalyzed by phosphofructokinase
why is galactose required in the body?
- formation of lactose in lactation
- constituent of glycolipids (cerebrosides), proteoglycans, & glycoproteins
enzyme that doesn’t act on glucose & its activity is not affected by fasting or by insulin
fructokinase
what enzyme cleaves F1P to D-glyceraldehyde & dihydroxyacetone phosphate?
aldolase B
how does d-glyceraldehyde enter glycolysis?
phosphorylation to GA3P catalyzed by TRIOKINASE
enzyme responsible for secretion of sorbitol into fetal blood
aldose reductase
enzyme responsible for conversion of sorbitol into fructose
sorbitol dehydrogenase
cataract is more severe if condition is caused by?
a defect in uridyl transferase
what substance accumulates in the eyes that is formed from galactose?
galactitol
inability to metabolize galactose occurs in _____? and best known cause for it is ______?
galactosemias, uridyl transferase deficiency
