Hexose Phosphate Shunt and Hexose Metabolism

Question 1

What is the first step in the fructose catabolism pathway?
What enzyme does this?
ATP dependent?
Any bi-products?

Answer 1

fructose to fruc-1-p by fructokinase using ATP hydrolysis

no bi-products

Question 2

What happens to fructose-1-p?
What enzyme does this?
ATP dependent?
Any bi-products?

Answer 2

converted to glyceraldehyde by aldolase B
no ATP
***bi-product: DHAP

Question 3

What happens to glyceraldehyde?
What enzyme does this?
ATP dependent?

Answer 3

converted to glyceraldehyde-3-p by triose kinase using ATP hydrolysis

Question 4

How many ATPs are consumed in the fructose pathway?

Answer 4

2

Question 5

Where does fructose metabolism primarily occur?

Answer 5

liver (and to some extent in the kidney)

Question 6

What are the isozymes of aldolase and where are they found?

Which ones act of fructose-1-p?

Answer 6

a- muscle
b- liver
c- brain

only B will recognize and act on fructose-1-p

Question 7

Which aldolase isozymes can act on fructose-1,6-bisphosphate?

Answer 7

a and b (muscle and liver)

Question 8

The pathway to synthesize fructose from glucose is called what?

Answer 8

polyol pathway

Question 9

What are the steps of the polyol pathway?

Answer 9

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)

Question 10

Where is the polyol pathway commonly found?

Answer 10

sperm

Question 11

What is essential fructosuria?

Answer 11

fructokinase deficiency, inherited

benign disease

Question 12

How could fructose directly enter glycolysis?

Answer 12

by phosphorylation by hexokinase to fru-6-p

Question 13

What is hereditary fructose intolerance?

Answer 13

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

Question 14

What are the steps of galactose metabolism?

Answer 14

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

Question 15

What is the net product of galactose metabolism?

Answer 15

glc-1-p and ADP

Question 16

What is nonclassical galactosemia do?

Answer 16

inhibits galactokinase activity

galactose accumulates

not as severe as classical

galactitol (derivative of galactose) may develop in lens of eyes causing cataracts

Question 17

What is classical galactosemia do?

Answer 17

inhibits galactokinase-1-p uridylyltransferase activity

Question 18

What is a main purpose of the pentose phosphate pathway? IMPORTANT

Answer 18

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)

Question 19

Where does the pentose phosphate pathway occur in the cell?

Answer 19

cytosol

Question 20

What happens in the 1st stage of the pentose phosphate pathway?

Answer 20

oxidative- generates 2 mol od NADPH per glc-6-p

Question 21

Is the first stage of the pentose phosphate pathway oxidative?

Answer 21

yes

Question 22

Is the second stage of the pentose phosphate pathway oxidative?

Answer 22

no.

Question 23

What happens in the 2nd stage of the pentose phosphate pathway?

Answer 23

ribose-5-phosphate is generated

Question 24

Notes on the oxidative stage of pentose pathway

Answer 24

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)

Question 25

What part of the pentose/phosphate pathway is NADPH generated on?

Answer 25

conversion of glc-6-p to 6-phosphogluconlactone by glucose-6-p dehydrogenase This is the rate limiting step of the pathway!!

Question 26

Why is conversion of glc-6-p to 6-phosphogluconlactone by glucose-6-p dehydrogenase the rate limiting step of the pentose-phosphate pathway?

Answer 26

because it is strongly (negatively) regulated by NADPH levels feedback-inhibition

Question 27

What is the main point behind the non-oxidative portion of the pentose-phosphate pathway?

Answer 27

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

Question 28

If the cell needs NADPH only, what are the oxidative and non oxidative parts of the PPP doing?

Answer 28

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

Question 29

If the cell needs NADPH and ribose-5-p, what are the oxidative and non oxidative parts of the PPP doing?

Answer 29

oxidative- makes ribulose-5-p to generate NADPH non-oxidative- isomerase converts ribulose-5-p to ribose-5-p

Question 30

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?

Answer 30

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

Question 31

If the cell needs NADPH and pyruvate, what are the oxidative and non oxidative parts of the PPP doing?

Answer 31

oxidative- on and making NADPH and ribulose-5-p non-oxdative- ribulose-5-p converted to fru-6-p and G3P to make pyruvate

Question 32

If ribulose-5-p is acted on by an isomerase, what happens?

Answer 32

ribose-5-p is made for nucleotide production

Question 33

If ribulose-5-p is acted on by an epimerase, what happens?

Answer 33

xylulose-5-p is made to be converted to fru-6-p and G3P for glycolysis remember that these pathways are reversible

Question 34

What glucose-6-p dehydrogenase deficiency result in? Walk through the steps

Answer 34

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

Question 35

What causes increased levels of H2O2?

Answer 35

oxidant stress, infections, drugs, fava beans

Question 36

How does metformin work against hyperglycemia?

Answer 36

it inhibits gluconeogenesis by inhibiting fructose-1,6-bisphosphatase activtity

Question 37

Why is metformin considered the first line treatment of type 2 diabetes?

Answer 37

it doesn't stimulate hypoglycemia or trigger weight gain

Question 38

How does sulfanouria work against hyperglycemia?

Answer 38

in increases insulin release from B pancreatic cells