35 PPP and Inter-conversion of Sugars Flashcards
this pathway is an alternative pathway for glucose 6-phosphate utilization: a shunt
the pentose phosphate pathway
what is the pentose phosphate pathway (PPP)?
an alternative pathway for glucose 6-phosphate utilization: a shunt (bypass) when there is excess G-6-P and can do a few things
1) you can pull electrons from the G6P and give them to 2 NADP+ and make 2 NADPH used in synthetic pathways like fatty acid synthesis, glutathione reduction , and other reactions like detoxification; the product being Ribulose 5 phosphate and then exchanged into ribose 5 phosphate for nucleotide biosynthesis
what is generated from the PPP?
generates intermediates of the glycolytic pathway, producing NADPH and ribose 5-phosphate for nucleotide synthesis in the process (made in different steps)
what important cofactor is produced from the PPP? why is this cofactor important?
NADPH
fatty acid biosynthesis
drug detoxification
the glutathione defense system against reactive oxygen species.
what are the two phases of the PPP?
oxidative and non-oxidative
what is the oxidative phase of the PPP?
consists of three reactions where NADPH is formed by three IRREVERSIBLE oxidation reactions converting glucose 6-P to a ketopentose + CO2
what is the non-oxidative phase of the PPP?
consists of 5 freely reversible reactions that produces ribose 5-P and glycolysis / gluconeogenesis intermediates
briefly write out the overall reaction of the PPP?
3 glucose-6-P + 6 NADP+ ->
3 CO2 + 6 NADPH + 6 H+ + 2 fuctose-6-P + glyceraldehyde-3-P
what are some pathways that require NADPH?
Detoxification
Reductive Synthesis
Detoxification
- reduction of oxidized glutathione
- cytochrome P450 monooxygenase
Reductive Synthesis
- fatty acid synthesis
- fatty acid chain elongation
- cholesterol synthesis
- NT synthesis
- DNA synthesis
- superoxide synthesis
since we know that in the PPP we know that glucose has an oxidative and non oxidative pathway, if the non oxidative pathway is chosen what two molecules can be used to make ribose 5 phosphate, what is this for?
fructose 6 phosphate and glyceraldehyde 3 phosphate; used for nucleoside biosynthesis, note that there are reversible pathways in the PPP
if NADPH levels are high, does the PPP still occur?
no, because NADPH is not in demand and negative feedback occurs
what is the point of the non-oxidative phase of the PPP?
source of Ribose-5-P for nucleotide synthesis – or reactions can lead back to glycolysis intermediates fructose-6-phosphate and glyceraldehyde-3-phosphate; note that they are completely interchangeable reactions
T/F, the reactions of phase 1 are irreversible?
T, they only occur if NADP+ is available
what stimulates the PPP?
Low NADPH / high NADP+
what inhibits the PPP?
High NADPH inhibits the pathway: shuts down part 1
T/F, the reactions of Phase 2 are all reversible?
these can function independently to meet metabolic needs for ribose 5-P or for glucose metabolism intermediates.
ex. Ribose 5-P can be used for nucleotide biosynthesis, unless the need for glycolysis is greater…ribulose-5-P will be diverted back into the glycolytic pathway.
what happens when NADPH levels are normal, what happens to the phases?
Phase 1 is shut down, but step 2 can operate as needed.
what phase of the PPP is the major source of NADPH in the cells? what is the key enzyme?
The oxidative phase; Glucose 6-phosphate dehydrogenase is the key enzyme for NADPH production and so a defect in this enzyme causes trouble
can NADPH be used by phagocytic cells? if so, how?
NADPH oxidase uses NADPH to form super oxide from O2 in the mechanism for killing microorganisms taken up by phagocytic cells.
how is NADPH used in relation to reactive oxygen species?
NADPH is central player in the defense against reactive oxygen species, especially in red blood cells.
NADPH helps to maintain glutathione in an active form.
Glutathione peroxidase : 2GSH + ROOH to GSSG + ROH + H2O
Glutathione reductase : GSSG + NADPH + H+ to 2GSH + NADP+
Pentose phosphate generates NADPH, which is needed in cellular defenses against ROS. NADPH supplies reducing power to glutathione reductase (3) to regenerate reduced GSH. If there is a glucose-6-phosphate dehydrogenase deficiency, the cell will not have the needed NADPH, and oxidized glutathione (GSSG) will build up and react with sulfhydryl groups on the hemoglobin molecule stimulating disulfide bond formation hemoglobin molecules become more cross linked creating heinz bodies. Without reduced GSH, glutathione will not have the reducing power to destroy H2O2.
RBC are especially prone to oxidative stress. H2O2 causes lipid peroxidation making the plasma membrane lipid bilayer fragile. Passage though narrow capillaries may make such RBC to rupture causing hemolytic anemia.
what is G-6-P dehydrogenase deficiency also considered?
G-6-P Dehydrogenase deficiency and its effect on RBC vitality is also considered a rare form of hemolytic anemia.
what is the main line of defense for RBC’s?
glutathione peroxidase
glutathione reductase
what is the only energy source that RBCs use?
glucose
in the red blood cells, why does pyruvate become lactate?
because it doesn’t have mitochondria and NADH is expended and the resulting NAD+ goes into the glycolytic pathway
what is the most abundant sugar in the diet? what other sugars are prevalent as well?
glucose; fructose and galactose
what are other disaccharides that can produce fructose and galactose?
sucrose (fructose-glucose)
lactose (galactose-glucose)
how are fructose and galactose utilized?
transported into the cells and phosphorylated on carbon 1 like glucose and kept inside for processing
what happens when fructose and galactose are phosphorylated?
once phosphorylated, fructose 1-P and galactose 1-P are metabolized to intermediates of the glucose metabolism
T/F, our bodies can synthesize any needed sugar from glucose?
t
what is the benefit of getting certain carbohydrates in our diet?
Immune function, wound healing, anti-cancer, anti-inflammatory systems, and much more
what are the eight important carbohydrates? are these essential? so what makes them important?
Mannose, galactose, glucose, fucose, xylose, N-acetylneuraminic acid, N-acetylglucosamine and N-acetylgalactosamine
no
But our nutritional status improves dramatically when we have these in adequate supply in out diet. They are conditionally essential.
what are the three essential sugars we talked about in class?
glucose, galactose and fructose
where is fructose metabolized?
in the liver
in terms of fructose metabolism in the liver, when fructose enters the cell what is it phosphorylated by and where, what is needed to make this happen?
fructose is phosphorylated at carbon 1 by fructokinase utilizing one ATP
what is fructose 1-P cleaved by in the liver? what is produced?
aldolase B; dihydroxyacetone and glyceraldehyde
where else have we seen Aldolase?
this is the same enzyme that cleaves fructose 1,6 bisphosphate in glycolysis
what is the effect of Aldolase B defect?
causes accumulation of F-1-P, which is bad
These patients need to avoid fructose! It stays in the digestive tract because it isn’t being taken up and bacteria use it and illness happens
what phosphorylates glyceraldehyde to glyceraldehyde 3-P during fructose metabolism in the liver?
triose kinase
in non-liver tissues for fructose metabolism, where is fructose phosphorylated and by what enzyme? where does this product go
fructose is phosphorylated at carbon 6 by hexokinase to form fructose 6-P which enters glycolysis
T/F, Hexokinase phosphorylates glucose preferentially, but will work on fructose
T
how many moles of ATP are used per mole of fructose to reach glycolytic intermediates?
two moles of ATP, subsequent yield of ATP is same as glycolysis
T/F, based on the needs of the body, if fructose is needed, glucose can be converted into fructose?
T
T/F, sperm cells use fructose as energy source while in seminal fluid, then glucose when in the female reproductive tract
T
if a male is fructose intolerant, should be be concerned about conceiving a baby?
no because you do not have to consume fructose to make fructose, glucose can be converted via isomerase to fructose
what is the difference between glucose and galactose?
glucose is -OH down at the carbon 4 and galactose is -OH up at the carbon 4
what are the two disease we discussed in class about faulty galactose interconversion?
Non-classical galactosemia
Classical galactosemia
what is Non-classical galactosemia?
Galactokinase is deficient and galactose can’t be processed
what is classical galactosemia?
can’t form UDP-galactose or make molecules dependent on UDP-galactose due to insufficient galactose 1-phosphate uridylyltransferase
Galactose-1-P accumulates in liver. Bad for liver cells
what are the fates of UDP-galactose?
in addition to UDP glucose performing this function, it can be used to produce glycosylated proteins and formation of milk sugar lactose in mammary glands
what is a specific example of the importance of a glucuronate?
it can be attached to bilirubin to become a glucuronide which increase solubility and then eliminated from the body. This adds negative charge and increases water solubility so the compounds can be moved and excreted; and this is how drugs are eliminated from the body
so how does udp-glucose become a glucuronate?
it becomes oxidized to glucuronate and then attached to bilirubin as glucuronide and then excreted
what is a glucuronate?
oxidation of UDP glucose
what is a glucuronide used for?
increasing the solubility of molecules
