Hexose Phosphate Shunt and Hexose Metabolism Flashcards
What is the first step in the fructose catabolism pathway?
What enzyme does this?
ATP dependent?
Any bi-products?
fructose to fruc-1-p by fructokinase using ATP hydrolysis
no bi-products
What happens to fructose-1-p?
What enzyme does this?
ATP dependent?
Any bi-products?
converted to glyceraldehyde by aldolase B
no ATP
***bi-product: DHAP
What happens to glyceraldehyde?
What enzyme does this?
ATP dependent?
converted to glyceraldehyde-3-p by triose kinase using ATP hydrolysis
How many ATPs are consumed in the fructose pathway?
2
Where does fructose metabolism primarily occur?
liver (and to some extent in the kidney)
What are the isozymes of aldolase and where are they found?
Which ones act of fructose-1-p?
a- muscle
b- liver
c- brain
only B will recognize and act on fructose-1-p
Which aldolase isozymes can act on fructose-1,6-bisphosphate?
a and b (muscle and liver)
The pathway to synthesize fructose from glucose is called what?
polyol pathway
What are the steps of the polyol pathway?
1) D-glucose to sobitol using aldolase reductase (using NADPH using giving off NADP+ and H)
2) sorbitol to D-fructose using sorbital dehydrogenase (using NAD+ and making NADH)
Where is the polyol pathway commonly found?
sperm
What is essential fructosuria?
fructokinase deficiency, inherited
benign disease
How could fructose directly enter glycolysis?
by phosphorylation by hexokinase to fru-6-p
What is hereditary fructose intolerance?
defect in aldolase B in liver
accumulation of fru-1-p is toxic
causes hypoglycemia by inhibiting glycolysis (ATP levels) so patients can’t do gluconeogenesis
What are the steps of galactose metabolism?
1) galactose to galactose-1-p by galactokinase (using ATP)
2) galactose-1-p + UDP-glucose to UDP galactose + glc-1-p using galactose-1-p uridylyltransferase
3) UDP-galactose to UDP-glucose using UDP glucose epimerase
4) UDP-glucose recycles
What is the net product of galactose metabolism?
glc-1-p and ADP
What is nonclassical galactosemia do?
inhibits galactokinase activity
galactose accumulates
not as severe as classical
galactitol (derivative of galactose) may develop in lens of eyes causing cataracts
What is classical galactosemia do?
inhibits galactokinase-1-p uridylyltransferase activity
What is a main purpose of the pentose phosphate pathway? IMPORTANT
generating NADPH for tons of other rxns (like FA synthesis) and ribose-5-phosphate for nucleotide synthesis (only if there is a need for nucleotides at that time)
Where does the pentose phosphate pathway occur in the cell?
cytosol
What happens in the 1st stage of the pentose phosphate pathway?
oxidative- generates 2 mol od NADPH per glc-6-p
Is the first stage of the pentose phosphate pathway oxidative?
yes
Is the second stage of the pentose phosphate pathway oxidative?
no.
What happens in the 2nd stage of the pentose phosphate pathway?
ribose-5-phosphate is generated
Notes on the oxidative stage of pentose pathway
There are several intermediates but just know that NADPH is generated on the first step (glu-6-p conversion) and CO2 is released in the last step (ribulose-5-p synthesis)
What part of the pentose/phosphate pathway is NADPH generated on?
conversion of glc-6-p to 6-phosphogluconlactone by glucose-6-p dehydrogenase
This is the rate limiting step of the pathway!!
Why is conversion of glc-6-p to 6-phosphogluconlactone by glucose-6-p dehydrogenase the rate limiting step of the pentose-phosphate pathway?
because it is strongly (negatively) regulated by NADPH levels
feedback-inhibition
What is the main point behind the non-oxidative portion of the pentose-phosphate pathway?
it is flexible. if nucleotides are needed, ribose-5-p is made. If not, intermediates are reconverted to fru-6-p and G3P and
the rxns are REVERSIBLE
If the cell needs NADPH only, what are the oxidative and non oxidative parts of the PPP doing?
oxidative- makes ribulose-5-p to generate NADPH
non-oxidative- ribulose converted to fru-6-p (and G3P) which is reconverted to glu-6-p to make more NADPH by going through the oxidative stage again
If the cell needs NADPH and ribose-5-p, what are the oxidative and non oxidative parts of the PPP doing?
oxidative- makes ribulose-5-p to generate NADPH
non-oxidative- isomerase converts ribulose-5-p to ribose-5-p
If the cell needs ribose-5-p only (i.e. NADPH levels are high), what are the oxidative and non oxidative parts of the PPP doing?
oxidative- glc-6-p dehydrogenase is inhibited by high levels of NADPH
non-oxidative- transketolase and transaldolase are used to convert fru-6-p and G3P to ribose-5-p
If the cell needs NADPH and pyruvate, what are the oxidative and non oxidative parts of the PPP doing?
oxidative- on and making NADPH and ribulose-5-p
non-oxdative- ribulose-5-p converted to fru-6-p and G3P to make pyruvate
If ribulose-5-p is acted on by an isomerase, what happens?
ribose-5-p is made for nucleotide production
If ribulose-5-p is acted on by an epimerase, what happens?
xylulose-5-p is made to be converted to fru-6-p and G3P for glycolysis
remember that these pathways are reversible
What glucose-6-p dehydrogenase deficiency result in? Walk through the steps
1) G6P dehydrogenase makes NADPH
2) NADPH is needed to reduce glutathione, which is critical for removing reactive oxygen species by donating hydrogen
3) so accumulation (caused by the deficiency) of reactive oxygen species causes hemolysis due to aggregation of hemoglobin near the plasma membrane which contributes to hemalytic anemia (also damages plasma membrane)
so this type of disease affects RBCs the most
What causes increased levels of H2O2?
oxidant stress, infections, drugs, fava beans
How does metformin work against hyperglycemia?
it inhibits gluconeogenesis by inhibiting fructose-1,6-bisphosphatase activtity
Why is metformin considered the first line treatment of type 2 diabetes?
it doesn’t stimulate hypoglycemia or trigger weight gain
How does sulfanouria work against hyperglycemia?
in increases insulin release from B pancreatic cells
