In this chapter, there is a detailed discussion of the metabolism of glycogen, the storage form of glucose, which is presented in Chapters 16 and 20.
The me tabolism of higher animals is dependent on the ability of the liver and muscles to maintain blood sugar levels.
The structure and the roles of glycogen are reviewed in the text.
Section 11.2.2 of Chapter 11 introduces you to the structure of glycogen.
The text shows the reactions of glycogen degradation and synthesis.
There is a discussion of the control of these reactions by allosteric mechanisms and the dephosphorylation of the key enzymes in response to hormonal signals.
The hormones allosteric effectors, as well as the hormones insulin, glucagon, and epinephrine, act as signals in the transduction pathways that control critical enzyme phosphorylations and dephosphorylations.
The text describes structures and control mechanisms for phosphorylase.
The differences in glycogen metabolism are related to the different functions of the tissues.
There is a discussion of the biochemical bases of several glycogen storage diseases in the final chapter.
You should be able to complete the objectives once you have mastered this chapter.
The brain and muscle do not have this enzyme.
There are a variety of binding sites, their functional roles, and the critical location of the phosphorylation andAMP binding sites near the subunit interface.
There are distinct pathways for the biosynthesis and degradation of glycogen.
Examples of glycogen storage diseases can be provided.
Von Gierke discovered a disease that can be caused by a deficiency in any of several different enzymes.
Use the appropriate prop erties from the right column to match the enzymes that degrade glycogen in the left column.
The reaction of the phosphoglucomutase is similar to the reaction of the glycolytic pathway.
Answer the questions about the degradation of amylose, a linear a-1,4 molecule of glucose that is stored in plants.
Which of the following substances have binding sites?
Give your major roles or effects.
The proper sequence for the reaction cascade of glycogen metabolism is listed below.
There is a defect in question 26.
The two branches are not long enough.
Four residues away from a branch point is where phosphorylase stops.
Residue G can be debranched by a-1,6-glucosidase.
The new a-1,6 linkage has to be at least four residues away from a branch point at a more internal site.
The larger mass of muscle stores more glycogen in toto.
After conversion to glucose 6-phosphate, the phosphorolytic cleavage of glycogen can produce glucose 1-phosphate.
These reactions don't have to have ATP.
On the other hand, hexokinase would have to be used to convert the sugars from glycogen to 6-phosphate.
It is more efficient to harvest the free energy by phosphorolytic cleavage than by hydrolytic one.
None of these are required to work.
The answer is incorrect because the group at one position on the small molecule is transferred to, and remains for one cycle of reaction on.
There is a difference between the product and the product that was present on the substrate.
The formation of glucose-1-P from glycogen doesn't consume theATP that would be required for the formation of glucose6-P fromglucose.
The net yield of ATP is three.
The effects ofAMP can be reversed with the help of sugar.
Another Pi is bound to serine 14.
The answers are incorrect due to the fact that calmodulin and Ca2+ bind to phosphorylase.
The phosphorylate is activated by the cAMP.
Ca2+ can be binding to calmodulin, which can be activated by phosphorylase kinase.
When calmodulin binding Ca2+, it undergoes changes in its structure.
The glycogen phosphorylase is activated by the activated kinase.
The effects lead to the degradation of muscle glycogen.
PP1's ability to act on its targets is reduced by the increasedphosphorylation of a subunit of PP1.
PP1 activity is decreased by a different mechanism when inhibitor 1 is phosphorylated by PKA.
PP1 can lead to increased levels of activated and inactivated phosphorylase.
Under these conditions, the breakdown of genes would be stimulated.
The phosphatase is more active when the hormone is activated.
The phosphatase dephosphorylates several genes.
The changes result in a decrease in the degradation of glycogen.
Enzymatic cascades lead from a small signal to a large response.
Small chemical signals can be amplified in a short time.
Their effects can be regulated at various levels.
The primer needed to start a new chain is formed by theidase glycogenin, which is attached to one of its tyrosine residues.
The primer that glycogen synthase can extend can be created by adding eightglucose to itself.
Despite a high ratio of orthophosphate to glucose 1-phosphate, the separate pathways allow the synthesis and degradation of glycogen.
The coordinated control of glycogen synthesis and degradation can be achieved through the separate pathways.
The branched structure allows simultaneous reactions to occur at many nonreducing ends, increasing the overall rates of degradation or synthesis.
The structure of glycogen will be normal since a defect in phosphofructokinase does not impair the ability of muscle to synthesise.
Some net accumulation of glycogen will occur because the utilization of glucose 6-phosphate in the glycolytic pathway is impaired.
The inability to perform strenuous exercise is likely due to the impaired glycolytic pathway in muscle.
The storage of extra glycogen will not become excessive because of the increased concentration of glucose 6-phosphate.
A patient can perform nonstrenuous tasks.
The levels of glycogen are slightly elevated relative to normal.
For a patient and a normal person, crude extracts from muscle are used to determine the activity of glycogen phosphorylase.
Explain the clinical and biochemical findings to the patient.
There is a response to calcium ion in a patient and a normal person.
A strain of mice has limited ability to engage incise.
These mice can only exercise on a treadmill for 30 percent of the time a normal mouse can.
After a rest, a Mutant mouse's blood sugar levels increase slightly, but they are still quite low.
The polymers have chains that are highly branched, with an average branch length of about 10 glucose residues in either a-1,4 or a-1,6 linkage.
The same type of structure is found in exhausted normal mice.
There is still a lot of branched genes from exhausted mice.
Your colleague has discovered a way to liberate the sugars from the wood.
The phosphorolytic cleavage of glucose from the nonreducing ends of cellulose is similar to the glycogen phosphorylase.
Consider a patient with a normal blood sugar level of 80 to 100 grams per 100 liters and a fast blood sugar level of 25 grams per 100 liters.
Feeding the patient will cause a rapid elevation of the blood sugar level, followed by a normal return to normal levels.
When the demand for oxygen exceeds the amount supplied through the circulation, contracting muscle becomes anaphylactic.
Lactate can accumulate in muscle.
Lactate can be converted to glycogen in muscle under certain conditions.
One line of evidence shows that CO2 can be used to convert pyruvate to malate, using NADPH as an electron donor.
The Cyclic nucleotide phosphatases are affected by caffeine.
A-1,6-glucosidase activity is exposed when a transferase shifts a chain of three glycosyl residues from one branch to another.
The unbranched chain can be further degraded by the release of freeglucose.
There are two reasons why cells want to convert most of the glycogen to sugar.
She found that there were no cleaved glycosyl residues.
Arsenate can be used in many reactions.
The ratio of pro tein phosphatase 1 to glycogen phosphorylase is 10 to 1.
A young woman can't exercise vigorously on the treadmill because of leg pains.
In contrast to the results of exercise in normal subjects, her lactate levels do not increase.
When the patient exercises or fasts, there is no significant hypoglycemia.
The level of muscle phosphorylase activity is normal despite the fact that the glycogen content is 10 times greater in the young woman.
In other experiments, 14C is quickly incorporated into fructose 6-phosphate and glycogen, but very little radioisotope is seen.
When 14C-pyruvate is added to another sample of the homogenate, the radioisotope is readily incorporated into glycogen.
If you want to confirm your conclusion, propose two more studies.
A seriously ill infant was described by Dr. D. H. Andersen in 1952.
A low elevation in the patient's blood sugar levels was noted when the patient was given the drug.
When the infant was fed galactose, normal elevation ofglucose was observed in the circulation.
The infant died at the age of 17 months, and Dr. Andersen found that the high concentration of glycogen in the body made it difficult to extract.
She sent the sample to Dr. Gerty Cori.
Dr. Cori put a sample with orthophosphate and two normal liver enzymes in a petri dish.
She found that the ratio of the two substances in the sample was 12:1 and 10:1, respectively.
Attach your answer to the relative insolubility of the glycogen in the autopsy sample.
One method for the analysis of glycogen is to culture a sample with io dide.
The mixture of methyl glucosides can be separated and analyzed.
A scheme to identify the specific lysine in the glycogen phosphorylase that is in the Schiff base linkage is needed.
Patients with Cori's disease lack the debranching enzyme, and therefore the structure of the body's tissues is unusual.
You can design an test that will allow you to show the presence of short branches in one of these patients.
Explain how you would show the deficiency of the debranching enzyme in these patients.
There are eight diseases that affect the level of glycogen in muscle and the structure of the polysaccharide in one or both of the tissues.
There is a disease of glycogen metabolism caused by a deficiency.
The affected subjects have low blood sugars.
After a meal, there are signs of hyperglycemia and high blood lactate.
The product of the phosphorylase is converted to the pathway component.
The reaction proceeds by way of a glucose 1,6-bisphosphate intermediate.
The calcium ion causes the muscle phosphorylase tophosphorylate.
The patient's glycogen phosphorylase activity is not as responsive to Ca2+ as it is in the normal subject.
It's possible that Ca2+ can't be activated in the patient because of the altered d subunit.
The rate of glycogen breakdown that is needed to sustain vigorous muscle contraction is not available because there are too few active glycogen phosphorylases.
When the activity of the phosphorylase in the muscle is lower than normal, there should be elevated levels of muscle glycogen.
The -1,6 linkage shows that a-1,6-glucosidase activity is deficient in the mutant strain.
Only a small number of ends with sugars are available as substrates.
Less energy is available for long exercise because of the limited ability to mobilize.
Each chain only has one nonreducing end that can be used for phosphorolysis.
Compared with the rate of breakdown of the molecule of glycogen, which has branched chains, the generation of the molecule from the plant could take a long time.
You would expect to find more nonreducing ends in the cells.
The relevant en zymes must be released to the extracellular space in order for the cells to degrade the large, insoluble macromolecule.
It seems unlikely that a phosphorylase would be a good choice for the degradation of cellulose because the negatively charged glucosephosphates wouldn't be able to cross cellular membranes and enter the cytosol.
Concentrations ofphosphate outside the cell could be too low to drive phosphorolysis.
The elevations in bloodglucose levels after feeding the patient are indicative of the release of glucose from the diet or other monosaccharides.
The lack of response to glucagon shows that the cascade is malfunctioning.
There is a possibility that you have a deficiency of the phosphorylase kinase.
The diseases described in Table 21.2 of the text include increased amounts of glycogen with normal structure.
A liver biopsy would be necessary for these purposes.
The conversion of 6-phosphate to 1-phosphate, the formation of UDP-glucose, and the transfer of the glucose to a primer chain can be accomplished.
The energy for vigorous muscle contraction is derived from the conversion of sugars.
The unnecessary hydrolysis of ATP would result from the simultaneous conversion of lactate to glycogen.
The formation of oxaloacetate through the action of the malic enzyme does not require the use ofATP, which is why the conversion of lactate to glycogen in muscle requires two fewer high-energy bonds.
There is a requirement for the synthesis of oxaloacetate from pyruvate.
The existing cyclicAMP is degraded.
The degradation of glycogen is prolonged by the inhibition of these enzymes because the remaining cyclicAMP continues to act.
The phosphorylase kinase is activated by the phosphorylgen phosphorylase.
Continuous activation of phosphorylase results in the continued release of sugars from the glycogen stores.
When phophorolysis produces it, there is no need for the glucose to be phosphorylated.
The molecule cannot diffuse across the cell membranes before it is utilized in the glycolytic pathway.
Alterations in the structure of the domain for glucosidase could affect the functioning of the transferase domain.
You would expect the metabolism and control of blood sugar in the body to be normal.
The structure of the glycogen should be the same in unaffected people as it is in Moderately increased concentrations of muscle glycogen could be expected.
After the ingestion of galactose in normal and affected people, you would expect a rise in blood sugar.
The extent to which glycogen is degraded in the muscle is limited by a defect in muscle phosphorylase.
The rise in blood lactate levels in the affected person would not be as high because this reduces the amount of lactate exported during exercise.
In patients with McArdle's disease, blood sugars increase in response to glucagon.
Even if the breakdown of glycogen is accelerated, it won't be able to be converted to glucose for export into the circulation because muscle doesn't have the ability to do so.
When arsenate is used as a substrate, it spontaneously hydrolyze to yield glucose and arsenate.
The conversion of sugar to pyruvate requires more than the conversion of sugar to 1-phosphate.
A phosphorylase to phosphatase ratio of one to one means that as soon as a few phosphorylase molecule are inactivated, phosphatase molecule that are no longer bound to phosphorylase begin to convert glycogen synthase molecule to the active form.
The wasteful hydrolysis of ATP occurs when genogen degradation and synthesis occur at the same time.
It appears that the pathway from pyruvate toglucose 6phosphate and on to glycogen is functional and that gluconeogenesis is working normally in the body.
The normal phosphorylase activity indicates that glycogen could be phosphorylized.
You should consider if there is a deficiency in the glycolytic pathway because it is not labeled when 14C-glucose is administered.
Fructose 6-phosphate can be made from radioactiveglucose in the sample, but knowledge about subsequent reactions is not available.
There could be a significant block.
A high rate of glycolytic activity during vigorous exercise cannot be accommodated because of a deficiency.
If you want to find out if there is a deficiency of one or more glycolytic enzymes, you should consider analyzing for additional radioactive glycolytic intermediates.
The description of the disorder is similar to a known condition for a deficiency in muscle phosphofructokinase.
One could argue that no lactate is generated during exercise because there is no lactate dehydrogenase.
The affected subjects can't exercise vigorously because they don't have enough glycogen in their muscle tissue.
Blocks of glucosyl are removed from a chain of a-1 4-linked residues and transferred internally to form a branch with an a-1 6 link.
The most important clue to the deficiency is found in the ratio of the two sugars to each other, which is 10 times higher in the affected infant than in a normal sample.
The action of phosphorylase, which phosphorylizes a-1 4 linkages, and the action of the glycogen debranching enzyme, which hydrolyzes a glucose in a-1 6 linkage, are the two ways in which the production of glucose 1-phosphate is done.
Treatment with a mixture of normal phosphorylase and debranching enzyme will yield a 10:1 ratio of sugar tophosphate.
There are far fewer branches in the autopsy sample, which yielded a ratio of 100:1.
The relative insolubility of the infant's glycogen, which has fewer branches, is similar to amylopectin, a linear glucosylpolymer which has limited solubility in water.
Feeding galactose will result in an increase in the concentration of sugar in the cell.
The levels of bloodglucose would not be elevated after galactose feeding because the levels of the deficient glucose 6-phosphatase were not converted to glucose.
Dr. Andersen used galactose feeding to increase the levels of glucose 6-phosphate in the liver cells because of the limited increase in blood sugar levels after the administration of epinephrine.
She concluded that the levels of thephosphatases in the blood were normal.
She considered other deficiencies that would result in the storage of abnormal amounts of liver glycogen.
CyclicAMP is negatively charged at neutral pH.
There is a relatively low rate of cross pollination.
The presence of two acyl chains on the molecule makes it much more hydrophobic, so that it can be easily dissolved in the bilayer and enter the cytosol.
In type IV glycogen-storage disease, there is a lower number of a-1,6 glycosidic linkages, which could be analyzed using methylation and hydrolysis.
There is a chance that the reducing end of the molecule will be converted to a compound.
In normal subjects, the ratio of trimethylglucose to dimethylglucose should be about 10 to 1, while a person with a deficiency in the branching enzyme will have a much higher ratio.
If you want to reduce the Schiff base linkage, you need to use sodium borohydride.
Various methods can be used to convert the protein to the peptide fragments.
This is a lengthy task because the protein is composed of two identical chains.
Acid hydrolysis can be performed on every isolated fragment that is known to contain lysine.
The pyridoxamine will be attached to one of the fragments with a lysine residue.
The analysis shows that pyridoxalphosphate is in the Schiff base linkage.
Mass spectrometry would be an easier way to identify the proteolytic fragment.
A small amount of a-1,4-glucosyl is found on the nonreducing side of a short outer branch.
Incubating a glycogen molecule with active phosphorylase and Pi will only liberate a small amount of sugar.
It is not possible to free the glucose molecule that is within four residues of a branch point.
If you want to show that phosphorylase action is limited by short outer branches, you can use a sample with a purified debranching enzyme and phosphorylase.
A patient with Cori's disease could be treated with active muscle phosphorylase and muscle extracts.
Only limited amounts of sugar 1-phosphate will be produced if debranching activity is low.
A normal person's muscle-cell extracts will be used to treat a normal glycogen sample.
When there is a low level of blood sugar in the air, the body's cells convert the glycogen in the body to aphosphates, which are converted to sugars in the blood.
It would be difficult for the liver to maintain proper levels of blood sugar.
After a meal, the body can't convert sugar to fuel.
The high concentration of the substrate may cause the conversion back to the original form of the molecule.
There would be an increase in the circulating blood sugar levels.
The elevation of lactate levels in blood suggests that any glucose in the body is converted to lactate.
It is expected that the percentage of glycogen in affected people will be lower.
Only a few patients with the disorder have glycogen in their body.
The dephosphorylated enzyme did not have the need for transfer to the incomingglucose 1-phosphate to form the bisphosphate intermediate.
A phosphorylated enzyme could be formed by replacing the covalently boundphosphate or the Phosphorous 1,6-bisphospate, which would bind to and phosphorylate phosphoglucomutase.
The mechanism is known.
Galac tokinase can yield galactose 1-phosphate and galactose 1-phosphate when it is present.
The latter gives UTP-glucose on the way to glycogen.
The unbranched a-amy lose has only one nonreducing end.
It is possible to release glucose from glycogen more quickly than it is from a-amylose.
Normally, branches occur in 10 units.
The ratio of sugar tophosphate is expected to be about 10:1.
An increased ratio shows that the glycogen has a lower degree of branching.
There is a defect in von Gierke's disease.
The T state is where the crystals are grown.
The R T equilibrium is shifted by the addition of glucose 1-phosphate.
The crystal shatters if it is not stable by chemical cross-links.
Haurowitz first observed the shattering of a crystal caused by an allosteric transition.
It is reasonable to expect that it can phosphorylate the dephosphate since it is an intermediate in the reaction.
The form of Glucose 1,6-bisphosphate is formed from the two substances.
Water is not allowed at the active site.
The entry of water could lead to the formation of sugar.
The site-specific mutagenesis experiment is revealing.
Tyr 573 is hydrogenbonded to the 2'-OH of a sugar molecule.
The wild-type enzyme has a ratio of 9000:1 and the Phe 573 Mutant has a ratio of 500:1.
A model building suggests that a water molecule occupies the site normally filled by the OH of tyrosine and occasionally attacks the oxocarbonium ion intermediate.
The synthesis function for glycogen is performed by Glycogenin.
Without a-amylase, the activity of glycogenin would be masked.
The a-amylase treatment stops the activity of glycogen synthase by shortening existing glucose chains below the threshold size required.
The product formed by the first and secondidases must leave and diffuse to each other.
If both active sites are close to the same molecule, the efficiency of the oxidizer will be increased.
A similar advantage can be obtained by holding the enzymes close to each other.
It will be very difficult to mobilize liver glycogen.
There will be little glycogen in the body.
The changes will lead to increased degradation.
There will be very little synthesis in its absence.
The a subunit of GS will remain active for too long and will encourage too much production of cAMP, which ultimately will keep glycogen phosphorylase active for too long.
There will be less available and impaired Glucose Mobilization.
The number and size of the granules will be very small.
The normal ability to regulate the blood sugar level will be missing from the organisms.
The degradation of glycogen can be prolonged by the slow phosphorylation of the a subunits.
The kinase can't be deactivated until it's phosphorylated.
The b subunit is more susceptible to dephosphorylation when it is phosphorylated.
The release of glucose from glycogen would be slowed because Phosphorylase kinase would be less active.