this chapter looked at the metabolic pathways for two other common dietary carbohydrates, fructose and galactose, as well as the pentose pathway, which produces NADPH and ribose 5-phosphate (used in nucleotide synthesis). fructose and galactose metabolism are similar in that they are basically phosphorylated and then converted into intermediates of the glycolytic pathway.
fructose metabolism:
1. fructose is phosphorylated to fructose 1-phosphate via fructokinase
2. fructose 1-phosphate is cleaved to DHAP and glyceraldehyde via aldolase B
3. glyceraldehyde phosphorylated to G3P via triose kinase
4. G3P and DHAP can be used in the glycolytic pathway
galactose metabolism:
1. galactose is phosphorylated to galactose 1-phosphate via galactokinase
2. galactose 1-phosphate plus UDP-glucose yields glucose 1-phosphate plus UDP-galactose
3. glucose 1-phosphate is converted to glucose 6-phosphate, which can be used in the glycolytic pathway.
production of fructose from glucose was also looked at in the "polyol" pathway:
1. glucose is reduced to sorbitol (polyol) via aldolase reductase, using NADPH as the reducing equivalents.
2. sorbitol is oxidized to fructose via sorbital dehydrogenase, producing NADH.
this conversion of glucose to fructose is used mainly in the seminiferous tubules, where spermatozoans use fructose instead of glucose in order to maintain the integrity of their plasma membrane (apparently glucose causes "acrosomal damage")
the pentose pathway is introduced as an alternate use of glucose 6-phosphate: instead of oxidizing for ATP, glucose 6-phosphate can taken through the pentose pathway to create NADPH (provides reducing equivalents, aids in catabolic reactions and helps protect against reactive oxygen species) and ribose 5-phosphate (used in nucleotide synthesis). the pentose pathway has two parts, an oxidative and non oxidative pathway. the oxidative pathway takes glucose 6-phosphate and creates 2 NADPH and ribulose 5-phosphate:
1. glucose 6-phosphate is oxidized to 6-phosphoglucanolactone via glucose 6 phosphate dehydrogenase, producing NADPH
2. 6-phosphoglucanolactone is hydrolyzed to 6-phosphoglucanolactate via glucanolactase
3. 6-phosphoglucanolactate undergoes oxidative decarboxylation to ribulose 5-phosphate, releasing CO2 and producing another NADPH
the non-oxidative portion of the pentose pathway takes three molecules of 5-ribulose phosphate, the product of the oxidative portion, and rearranges the molecules using transferases to eventually form 2 molecules of fructose 6-phosphate and 1 molecule of G3P. the reactions are as follows:
1. out of 3 molecules of 5-ribulose phosphate, 2 are converted to xylulose 5-phosphate via epimerases
2. the 3rd molecule of 5-ribulose phosphate is converted to ribose 5-phosphate (which can be used for nucleotide synthesis if necessary)
3. xylulose 5-P and ribose 5-P are rearranged to G3P and sedoheptulose 7-P via transketolase
4. sedoheptulose 7-P and G3P are rearranged to fructose 6-P and erythrose 4-P via transaldolase
5. erythrose 4-P and xylulose 5-P are rearranged to fructose 6-P and G3P
thus, 3 molecules of ribulose 5-phosphate are converted to 2 molecules of fructose 6-phosphate and one molecule of G3P.
we then look at how the pentose pathway can be used to accommodate and balance cellular needs for ATP, ribose 5-phosphate, and NADPH. several scenarios are considered-- when only NADPH is needed, only the oxidative portion of the pathway is activated, producing two molecules of NADPH per glucose molecule, and the nonoxidative pathway converts ribulose 5-phosphate to glucose 6-phosphate (presumably by isomerization of fructose 6-phosphate) which is then put back into the oxidative portion to create even more NADPH. when NADPH and ribose 5-phosphate are both needed, the oxidative pathway is activated to produce NADPH, and ribose 5-phosphate is produced from the non-oxidative pathway via isomerase. when only ribose 5-phosphate is needed, this implies that NADPH levels are relatively high-- which actually inhibits the first enzyme in the oxidative pathway. thus the oxidative pathway is inhibited, but the nonoxidative pathway produces ribose 5-phosphate from ribulose 5-phosphate. finally, in the case when NADPH and pyruvate are needed, both the oxidative and non oxidative portions are stimulated.
questions
1. describe the mechanism for the metabolism of fructose.
2. where does metabolism of fructose occur?
3. describe the mechanism for the polyol pathway.
4. where is the polyol pathway mainly used and why?
5. what is the galactose metabolism pathway?
6. what does the pentose pathway produce and why are the products useful?
7. why is NADP+ used instead of NAD+?
8. describe the mechanism for the oxidative branch of the pentose pathway.
9. describe the mechanism for the non-oxidative branch of the pentose pathway.
10. describe how the glycolytic intermediates can be used to produce ribose 5-phosphate for nucleotide synthesis.
11. what are some uses of NADPH in the body?
12. the entry of glucose 6-phosphate into the pentose phosphate pathway is regulated by...
describe how the pentose phosphate pathway is used to respond to cellular needs for:
13. NADPH
14. NADPH and ribose 5-phosphate
15. ribose 5-P only
16. NADPH and pyruvate
answers
1. fructose is phosphorylated by fructokinase to fructose 1-phosphate. fructose 1-phosphate is cleaved by aldosase B into DHAP and glyceraldehyde. glyceraldehyde is phosphorylated by triose kinase into G3P. G3P can then be converted to 1,3 bisphosphoglycerate in the glycolytic pathway or combined with DHAP to form fructose 1,6 bisphosphate in the gluconeogenic / glycolytic pathway.
2. mainly in the liver, but also in the mucosa of the small intestine.
3. glucose is reduced to sorbitol (polyol) by aldolase reductase, forming NADPH. sorbitol is oxidized to fructose via sorbitol dehydrogenase.
4. glucose conversion into fructose is mainly used in the seminal vescicles, which store the spermatozoans. spermatozoans use fructose rather than glucose to avoid plasma membrane damage while in the male reproductive system.
5. galactose is phosphorylate by galactokinase to galactose 1-phosphate. galactose 1-phosphate is converted to glucose 1-phosphate via galactose 1-phosphate uridylyltransferase. glucose 1-phosphate is then isomerized to glucose 6 phosphate for use in other metabolic pathways.
6. an alternative pathway to the first few steps of glycolysis that produces ribose 5-phosphate, which is used in nucleotide synthesis, and NADPH, which is used in reductive detoxification.
7. NADPH is used in reactions that have need for reducing equivalents because the ratio of NADPH to NADP+ is much higher than that of NADH to NAD (because NADH is immediately used in the electron transport chain)
8. glucose 6-phosphate is oxidized to 6-phosphogluconolactone via glucose 6-phosphate dehydrogenase (producing NADPH). 6-phosphogluconolactone is hydrolyzed to 6-phosphogluconolactate via gluconolactase. 6-phosphate gluconolactate undergoes oxidative decarboxylation to ribulose 5 phosphate, releasing CO2 and forming NADPH.
9. 3 molecules of ribulose 5-phosphate are converted via isomerases, epimerases, transketolases, and transaldolases into two molecules of fructose 6-phosphate and one molecule of G3P, which can be used in glycolysis.
10. ribose 5-phosphate can be synthesized using the non-oxidative portion of the pentose pathway because the reactions are reversible. 2 molecules of fructose 6-phosphate and 1 molecule of G3P can ultimately produce 3 molecules of ribose 5-phosphate.
11. NADPH is mainly produced from the oxidative portion of the pentose pathway and is used to provide reducing equivalents and is involved in protecting the body against reactive oxygen species. it is also involved in anabolic processes such as cholesterol synthesis, fatty acid synthesis and chain elongation.
12. the concentration of NADPH in the cell. high NADPH inhibits glucose 6-phosphate dehydrogenase.
13. the oxidative portion of the pentose phosphate pathway is utilized to produced 2 moles of NADPH per molecule of glucose. the non oxidative portion of the pentose pathway is used to convert ribulose 5-phosphate back to glucose 6-phosphate, where it can be used to generated more NADPH.
14. the oxidative portion creates NADPH and ribulose 5-phosphate. isomerases convert ribulose 5 phosphate into ribose 5-phosphate.
15. high levels of NADPH will inhibit the oxidative portion; just the non-oxidative portion will create ribose 5-phosphate from fructose 6-phosphate and G3P.
16. the oxidative portion will create NADPH and the nonoxidative will create fructose 6-phosphate and G3P, which can be used in glycolysis to produce pyruvate.
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