Term
|
Definition
| very large, branched polymer of glucose residues |
|
|
Term
| the linkage between most of the glucose residues in glycogen |
|
Definition
|
|
Term
| frequency of branching in glycogen |
|
Definition
|
|
Term
| type of linkage at branch points in glycogen |
|
Definition
|
|
Term
| why glycogen is not as energy rich as fatty acids |
|
Definition
| because glycogen is less reduced (more oxidized) than fatty acids |
|
|
Term
| one advantage of glycogen over fatty acids |
|
Definition
| the glucose released from glycogen can provide energy in the absence of oxygen, while fatty acids can't |
|
|
Term
| what glycogen does for blood glucose |
|
Definition
| maintains blood glucose concentration between meals |
|
|
Term
| when the brain can use a fuel other than glucose |
|
Definition
| during prolonged starvation |
|
|
Term
| plants store glucose as... |
|
Definition
|
|
Term
| the 2 major sites of glycogen storage in humans |
|
Definition
|
|
Term
| glycogen is present in the cytoplasm as... |
|
Definition
| 10-40 nm granules, containing about 55,000 glucose molecules |
|
|
Term
| why glycogen synthesis and degradation are regulated in the liver |
|
Definition
| to maintain glucose concentration in the blood, such as to degrade glycogen between meals |
|
|
Term
| why glycogen synthesis and degradation are regulated in the liver |
|
Definition
| to meet the needs of the muscle itself, such as to meet ATP needs |
|
|
Term
| this is thought to be a major component of exhaustion |
|
Definition
| depletion of muscle glycogen |
|
|
Term
| depiction of the structure of glycogen |
|
Definition
|
|
Term
| the protein at the core of glycogen |
|
Definition
|
|
Term
| these form the ends of the glycogen granule |
|
Definition
| the nonreducing ends of the glycogen molecule |
|
|
Term
| some steps required for the efficient breakdown of glycogen |
|
Definition
-degrade glycogen
-remodel glycogen so that it remains a substrate for degradation
-convert the product of glycogen breakdown into a product suitable for further metabolism |
|
|
Term
| the key regulatory enzyme in glycogen breakdown |
|
Definition
|
|
Term
|
Definition
| the key regulatory enzyme in glycogen breakdown; it cleaves its substrate by the addition of orthophosphate (Pi) to yield glucose 1-phosphate |
|
|
Term
|
Definition
| the cleavage of a bond by the addition of orthophosphate |
|
|
Term
| depiction of the function of glycogen phosphorylase |
|
Definition
|
|
Term
| where glycogen phosphorylase catalyzes the removal of glucose molecules from glycogen |
|
Definition
| the nonreducing ends of the glycogen molecule, that is, it cleaves off the residues at the ends of the chains |
|
|
Term
|
Definition
|
|
Term
| how the glucose 1-phosphate released by the phosphorolysis of glycogen can become useful |
|
Definition
| it can be readily converted into glucose 6-phosphate, which is an important metabolic intermediate |
|
|
Term
|
Definition
| converts glucose 1-phosphate into glucose 6-phosphate |
|
|
Term
| depiction of phosphorolysis |
|
Definition
|
|
Term
| depiction of the branching in glycogen |
|
Definition
|
|
Term
| why the phosphorolytic cleavage of glycogen is energetically advantageous |
|
Definition
| because the released sugar is already phosphorylated |
|
|
Term
| why phosphorolytic cleavage of glycogen is advantageous over hydrolytic cleavage of glycogen |
|
Definition
| because phosphorolytic cleavage releases a sugar that is already phosphorolated, while the unphosphorylated sugar released by hydrolysis would have to be later phosphorolated at the expense of an ATP to enter the glycolytic pathway |
|
|
Term
| additional advantage of glycohen phosphorolysis in muscle cells |
|
Definition
| can't be transported out of the cell, since there's no transporters for it |
|
|
Term
| when glycogen phosphorolase stops degrading glycogen |
|
Definition
| when it reaches a residue 4 residues away from a branch point |
|
|
Term
| what enzymes remodel the glycogen such that glycogen phosphorolase can continue degrading it? |
|
Definition
-a transferase
-α-1,6-glucosidase (aka debranching enzyme) |
|
|
Term
| what transferase does to glycogen |
|
Definition
| shifts a block of 3 glucosyl residues from one outer branch to another, exposing a single α-1,6-glycosidic linked, branched, glucose residue |
|
|
Term
| what α-1,6-glucosidase (aka debranching enzyme) does to glycogen |
|
Definition
| hydrolyzes the α-1,6-glycosidic bond at the branching glucose residue |
|
|
Term
| depiction of the function of α-1,6-glucosidase (aka debranching enzyme) |
|
Definition
|
|
Term
|
Definition
| phosphorylates a free glucose molecule |
|
|
Term
| where the activities of transferase and α-1,6-glucosidase (aka debranching enzyme) are in eukaryotes |
|
Definition
| a single 160-kDa polypeptide chain, that is, a bifunctional enzyme |
|
|
Term
| depiction of glycogen remodeling |
|
Definition
|
|
Term
| what must happen t the glucose 1-phosphate formed in the phosphorolytic cleavage of glycogen before it can enter the metabolic mainstream? |
|
Definition
| has to be converted into glucose 6-phosphate |
|
|
Term
|
Definition
| catalyzes the shift of a phosphoryl group to convert glucose 1-phosphate into glucose 6-phosphate |
|
|
Term
| depiction of the function of phosphoglucomutase |
|
Definition
|
|
Term
| when the liver releases glucose into the blood |
|
Definition
| during muscular activity and between meals |
|
|
Term
| why liver can release glucose |
|
Definition
| because it has glucose 6-phosphatase, a hydrolytic enzyme absent in muscle |
|
|
Term
|
Definition
| removes the phosphoryl group from glucose 6-phosphate to yield free glucose and Pi (orthophosphate) |
|
|
Term
| depiction of the function of glucose 6-phosphatase |
|
Definition
|
|
Term
| role of glucose 6-phosphatase in anoyther biochemical pathway we've already discussed |
|
Definition
| releases free glucose at the end of gluconeogenesis |
|
|
Term
| where glucose 6-phosphatase is found inside liver cells |
|
Definition
| on the lumenal side of the smooth ER membrane |
|
|
Term
| what happens to glucose 6-phosphate in liver cells? |
|
Definition
| glucose 6-phosphate gets transported into ER; glucose and Pi (ortyhophosphate) are then shuttled back into the cytoplasm |
|
|
Term
| what tissues other than liver use glucose 6-phosphate for |
|
Definition
|
|
Term
| is glucose a major fuel for the liver? |
|
Definition
|
|
Term
| some things that regulate glycogen phosphorylase |
|
Definition
-several allosteric effectors that signal the energy state of the cell
-reversible phosphorylation |
|
|
Term
| reversible phosphorylation is responsive to... |
|
Definition
hormones, such as...
-epinephrine
-glucagon
-insulin |
|
|
Term
| why liver and skeletal muscle muscle have different forms of glycogen phosphorylase |
|
Definition
| because the liver maintains glucose homeostasis for the organism as a whole while the skeletal muscle uses glucose to produce energy for itself |
|
|
Term
| the 2 interconvertible forms of dimeric phosphorylase in the liver |
|
Definition
-usually active phosphorylase a
-usually inactive phosphorylase b |
|
|
Term
| the usually active form of glycogen phosphorylase in the liver |
|
Definition
|
|
Term
| the usually inactive form of glycogen phosphorylase in the liver |
|
Definition
|
|
Term
|
Definition
| enzymes coded by different genes, but catalyze same rxn |
|
|
Term
| state favored by e'librium for phosphorylase a |
|
Definition
|
|
Term
| state favored by e'librium for phosphorylase b |
|
Definition
|
|
Term
| depiction of the structures of phosphorylase a and phosphorylase b |
|
Definition
|
|
Term
| depiction of phosphorylase regulation and its e'librium |
|
Definition
|
|
Term
| then role of glycogen degradation in the liver |
|
Definition
| to form glucose for export to other tissues when blood glucose is low |
|
|
Term
| the default state of liver phosphorylase |
|
Definition
| a form (R state); degrades glycogen to release glucose unless signaled otherwise |
|
|
Term
| molecule that inhibits liver phosphorylase |
|
Definition
|
|
Term
| depiction of the allosteric regulation of liver phosphorylase |
|
Definition
|
|
Term
| why glycogen is not mobilized when glucose is already abundant |
|
Definition
| because glucose inhibits phosphorylase |
|
|
Term
| why is muscle phosphorylase (phosphorylase b) usually in the T state? |
|
Definition
| because phosphorylase needs to be active primarily during muscle contraction |
|
|
Term
| what activates muscle phosphorylase (phosphorylase b) into the R state? |
|
Definition
| high concentrations of AMP |
|
|
Term
| how muscle phosphorylase (pjhosphorylase b) is activated into the R state |
|
Definition
| AMP binds to the nucleotide binding site and stabilizes the R state |
|
|
Term
| how AMP and ATP regulate muscle phosphorylase (phosphorylase b) |
|
Definition
| they compete with each other for the same site on the phosphorylase b enzyme; therefore, phosphorylase b is regulated by the energy charge of the cell |
|
|
Term
| the transition of muscle phosphorylase (phosphorylase b) is regulated by... |
|
Definition
| the energy charge of the cell |
|
|
Term
| why muscle phosphorylase (phosphorylase b) is usually inactive under physiological conditions |
|
Definition
| because of the inhibitory effects of ATP and glucose 6-phosphate |
|
|
Term
| depiction of the allosteric regulation of muscle phosphorylase |
|
Definition
|
|
Term
| the similarity between liver and muscle phosphorylase |
|
Definition
| 90% identical in amino acid sequence, but the 10% difference confers important differences |
|
|
Term
| different types of fiber in skeletal muscle |
|
Definition
-type I (slow-twitch)
-type IIa (intermediate between type I and type IIb)
-type IIb (fast-twitch) |
|
|
Term
| primary fuel source for type I (slow-twitch) muscle fibers |
|
Definition
| fatty acid degradation and cellular respiration; rich in mitochondria |
|
|
Term
| primary fuel source for type I (fast-twitch) muscle fibers |
|
Definition
|
|
Term
| how phosphorylase b is converted into phosphorylase a |
|
Definition
| by the phosphorylation of a single serine residue in each subunit |
|
|
Term
| what causes phosphorylase b in liver to convert into phosphorylase a? |
|
Definition
|
|
Term
| what causes phosphorylase b in muscle to convert into phosphorylase a? |
|
Definition
|
|
Term
|
Definition
| catalyzes the conversion of phosphorylase b to phosphorylase a |
|
|
Term
| the transition from the T state (prevalent in phosphorylase b) to the R state (prevalent in phosphorylase a) is associated with... |
|
Definition
| structural changes in α helices that move a loop out of the active site of each subunit |
|
|
Term
| why the active site of phosphorylase is less active in the T state |
|
Definition
| because it is partly blocked |
|
|
Term
| why tyhe R state of phosphorylase is more active |
|
Definition
| because the active site is open and a binding site for orthophosphate (Pi) is well organized |
|
|
Term
| how phosphorylase kinase activates phosphorylase b |
|
Definition
| by attaching a phosphoryl group |
|
|
Term
|
Definition
| Ca binding protein that functions as a Ca sensor that stimulates many enzymes in eukaryotes |
|
|
Term
| the part of phosphorylase kinase occupied by calmodulin |
|
Definition
|
|
Term
| the parts of phosphorylase kinase that are the targets of protein kinase A (PKA) |
|
Definition
|
|
Term
| sequence of phosphorylation of phosphorylase kinase |
|
Definition
| the β unit is phosphorylated first, followed by the α unit |
|
|
Term
| when activation of phosphorylase kinase is initiated |
|
Definition
| when Ca2+ binds to the δ subunit (calmodulin) |
|
|
Term
| contraction of muscle is triggered by... |
|
Definition
| the release of Ca2+ from the sarcoplasmic reticulum |
|
|
Term
| maximal activation of phosphorylase kinase is achieved with... |
|
Definition
| the phosphorylation of the α and β subunits when of the Ca2+ bound kinase |
|
|
Term
| depiction of the activation of phosphorylase kinase |
|
Definition
|
|
Term
| sequence of activation in activating phosphorylase |
|
Definition
| PKA activates phosphorylase kinase, which activates glycogen phosphorylase |
|
|
Term
| 2 hormones that signal the need for glycogen breakdown |
|
Definition
|
|
Term
| what leads to the release of epinephrine? |
|
Definition
| muscular activity or its anticipation |
|
|
Term
| the hormone liver is more responsive to |
|
Definition
|
|
Term
|
Definition
|
|
Term
| depiction of the hormonal control of glycogen breakdown |
|
Definition
|
|
Term
| how hormones trigger the breakdown of glycogen |
|
Definition
| they initiate a cyclic AMP (cAMP) signal-transduction cascade |
|
|
Term
| depiction of the regulatory cascade for glycogen breakdown |
|
Definition
|
|
Term
| this leads to maximal mobilization of liver glycogen |
|
Definition
| stimulation by both glucagon and epinephrine |
|
|
Term
| when is glycogen synthesis turned off? |
|
Definition
| when glucose needs have been met |
|
|
Term
| how is glycogen breakdown turned off? |
|
Definition
phosphorylase kinase and glycogen phosphorylase are dephosphorylated and inactivated
simultaneously, glycogen synthesis is activated |
|
|
Term
| protein phosphatase 1 (PP1) |
|
Definition
| removes phosphoryl groups from phosphorylase kinase and glycogen phosphorylase into the less active b form, inactivating them; this helps turn off glycogen breakdown when need be |
|
|
Term
| advantage of separate pathways being used in synthesis and breakdown |
|
Definition
| much greater flexibility, both in energetics and control |
|
|
Term
| common requirement for biosynthesis |
|
Definition
| use of an activated precursor |
|
|
Term
| precursor used in glycogen synthesis |
|
Definition
| uridine diphosphate glucose (UDP-glucose) |
|
|
Term
| structure of uridine diphosphate glucose (UDP-glucose) |
|
Definition
|
|
Term
| overall pathway of glycogen synthesis |
|
Definition
| glycogenn + UDP-glucose --> glycogenn+1 + UDP |
|
|
Term
| overall pathway of glycogen degradation |
|
Definition
| glycogenn+1 + Pi --> glycogenn + glucose 1-phosphate |
|
|
Term
| the activated form of glucose used in the synthesis of glycogen |
|
Definition
|
|
Term
| UDP-glucose is synthesized from... |
|
Definition
| glucose 1-phosphate and uridine triphosphate (UTP) |
|
|
Term
| rxn that yields UDP-glucose |
|
Definition
| glucose 1-phosphate + UTP <--> UDP-glucose + PPi |
|
|
Term
| UDP-glucose phosphorylase |
|
Definition
| catalyzes the synthesis of UDP-glucose from glucose 1-phosphate and UTP |
|
|
Term
| depiction of the synthesis of UDP-glucose from glucose 1-phosphate and UTP |
|
Definition
|
|
Term
| depiction of the function of UDP-glucose phosphorylase |
|
Definition
|
|
Term
| by itself, the synthesis of UDP-glucose is readily reversible. what is it coupled with to make it irreversible? |
|
Definition
| the essentially irreversible hydrolysis of pyrophosphate (PPi) into orthophosphate (2 Pi) |
|
|
Term
| what drives the synthesis of UDP-glucose? |
|
Definition
| the essentially irreversible hydrolysis of pyrophosphate (PPi) into orthophosphate (2 Pi) |
|
|
Term
| inorganic pyrophosphatase |
|
Definition
| catalyzes the essentially irreversible hydrolysis of pyrophosphate (PPi) into orthophosphate (2 Pi) |
|
|
Term
| depiction of UDP-glucose synthesis being coupled with pyrophosphate (PPi) hydrolysis |
|
Definition
|
|
Term
| importance of the essentially irreversible hydrolysis of pyrophosphate (PPi) into orthophosphate (2 Pi) elsewhere in biochem |
|
Definition
| drives many biosynthetic rxns |
|
|
Term
| where new glucosyl units are added to glycogen during glycogen synthesis |
|
Definition
| the nonreducing terminal residues of glycogen |
|
|
Term
|
Definition
| catalyzes the transfer of glucose from UDP-glucose to a growing chain |
|
|
Term
| the key regulatory enzyme in glycogen synthesis |
|
Definition
|
|
Term
| the 2 isozymic forms of glycogen synthase in humans |
|
Definition
-one specific to the liver
-the other expressed in muscle and other tissues |
|
|
Term
| where glycogen synthase can add glucosyl residues |
|
Definition
| only where there's a polysac chain containing 5+ residues |
|
|
Term
|
Definition
catalyzes the formation of α-1,4-glucose polymers
this is the primer for glycogen synthesis |
|
|
Term
| depiction of a cross section of a glycogen molecule |
|
Definition
|
|
Term
| how glycogen gets branched |
|
Definition
| a branching enzyme breaks α-1,4 linkages and forms branches with α-1,6 linkages to the main chain |
|
|
Term
| function of branching enzyme |
|
Definition
| breaks α-1,4 linkages and forms branches with α-1,6 linkages to the main chain |
|
|
Term
| how exact branching enzyme is |
|
Definition
-the block of 7 or so residues must contain the nonreducing terminus and come from a chain 11+ residues long
-the new branch point must be 4+ residues away from a preexisting one |
|
|
Term
| depiction of the branching rxn in glycogen synthesis |
|
Definition
|
|
Term
| why branching is important for glycogen |
|
Definition
-increases solubility of glycogen
-increases number of terminal residues, increasing rate of glycogen synthesis and degradation |
|
|
Term
| the 2 forms of glycogen synthase |
|
Definition
|
|
Term
| a form of glycogen synthase |
|
Definition
| active, nonphosphorylated form |
|
|
Term
| b form of glycogen synthase |
|
Definition
| inactive, phosphorylated form |
|
|
Term
| the key means of regulating glycogen synthase |
|
Definition
| allosteric regulation of the phosphorylated b form |
|
|
Term
| powerful activator of glycogen synthase b |
|
Definition
| glucose 6-phosphate, which stabilizes the R state |
|
|
Term
| glycogen synthase kinase (GSK) |
|
Definition
| phosphorylates glycogen synthase |
|
|
Term
| what regulates glycogen synthase kinase (GSK)? |
|
Definition
-insulin
-protein kinase A (PKA) |
|
|
Term
| effects of phosphorylation glycogen synthase and glycogen phosphorylase |
|
Definition
opposite effects
activates phosphorylase and inactivates synthase |
|
|
Term
| nucleoside diphosphokinase |
|
Definition
| catalyzes the regeneration of UTP from UDP |
|
|
Term
| the summation of the rxns in glycogen synthesis |
|
Definition
| 1: glucose + ATP --> glucose 6-phosphate + ADP
2: glucose 6-phosphate --> glucose 1-phosphate
3: glucose 1-phosphate + UTP --> UDP-glucose + PPi
4: PPi + H2O --> 2 Pi
5: UDP-glucose + glycogenn --> glycogenn+1 + UDP
6: UDP + ATP --> UTP + ADP
sum: glucose + 2 ATP + glycogenn + H2O --> glycogenn+1 + 1 ADP + 2 Pi |
|
|
Term
| the overall efficiency of glycogen storage |
|
Definition
|
|
Term
| glucagon and epinephrine control both glycogen breakdown and synthesis through... |
|
Definition
|
|
Term
| how glycogen synthesis and breakdown are reciprocally regulated |
|
Definition
| phosphorylation activates glycogen phosphorylase and inactivates glycogen synthase |
|
|
Term
| depiction of the coordinate control of glycogen metabolism |
|
Definition
|
|
Term
| protein phosphatase 1 (PP1) |
|
Definition
| catalyzes dephosphorylation of glycogen phosphorylase and glycogen synthase |
|
|
Term
| how protein phosphatase 1 (PP1) |
|
Definition
catalyzes dephosphorylation of glycogen phosphorylase and glycogen synthase
inhibits phosphorylase a and phosphorylase kinase by dephosphorylating them
activates glycogen phosphorylase b into glycogen phosphorylase a by dephosphorylating it |
|
|
Term
| depiction of the regulation of glycogen synthesis by protein phosphatase 1 (PP1) |
|
Definition
|
|
Term
|
Definition
| catalytic subunit of protein phosphatase 1 (PP1) in muscle |
|
|
Term
|
Definition
| catalytic subunit of protein phosphatase 1 (PP1) in liver |
|
|
Term
| the role of regulatory subunits (GM and GL) in the context of glycogen |
|
Definition
| they act as scaffolds, bringing together the protein phosphatase and its substrates in the context of a glycogen particle |
|
|
Term
| how protein phosphatase 1 (PP1) is regulated in muscle |
|
Definition
| 1: phosphorylation, which releases PP1 from GM
2: phosphorylated inhibitors that inhibit PP1 |
|
|
Term
| depiction of the regulation of protein phosphatase 1 (PP1) in muscle |
|
Definition
|
|
Term
| how insulin regulates blood glucose |
|
Definition
| increases amount of glucose in cell and stimulates synthesis of glycogen |
|
|
Term
| how insulin stimulates glycogen synthesis |
|
Definition
-increases glucose in cell by increasing number of glucose transporters (GLUT4) in cell membrane
-leads to the inactivation of glycogen synthase kinase, which leads to the activation of glycogen synthase |
|
|
Term
| depiction of how insulin inactivates glycogen synthase kinase |
|
Definition
|
|
Term
|
Definition
| insulin-receptor substrate |
|
|
Term
| what insulin binds to in te plasma membrane |
|
Definition
| its receptor tyrosine kinase |
|
|
Term
|
Definition
| replenishment of glycogen stores |
|
|
Term
| other than insulin, this can signal the liver to synthesize glycogen |
|
Definition
| blood glucose concentration |
|
|
Term
| what happens to liver phosphorylase a when glucose is infused into the blood? |
|
Definition
| the amount of liver phosphorylase a rapidly decreases |
|
|
Term
| this is the glucose sensor in liver cells |
|
Definition
|
|
Term
| how glucose regulates inactivates phosphorylase A |
|
Definition
| binding of glucose to phosphorylase a shifts it from the R form to the T form, making PP1 dissociate from it to make the phosphorylase b, stabilizing the T form |
|
|
Term
| is the R <--> T transition of muscle phosphorylase a affected by glucose? |
|
Definition
| no; therefore, it is not affected by blood glucose concentration |
|
|
Term
| the conversion of phosphorylase a into phosphorylase b is accompanied by... |
|
Definition
|
|
Term
| PP1 activates ______ and inactivates ______ |
|
Definition
glycogen synthase
glycogen phosphorylase |
|
|
Term
| when the activity of gycogen synthase begins to increase |
|
Definition
| only after most of the phosphorylase is inactivated |
|
|
Term
| advantage of the lag between glycogen degradation and glycogen synthesis |
|
Definition
| prevents the 2 pathways from operating simultaneously |
|
|
Term
| the 3 elements of the remarkable glucose-sensing system in the liver |
|
Definition
1: communication between the allosteric site for glucose and the serine phosphate
2: the use of PP1 to inactivate phosphorylase and activate glycogen synthase
3: the binding of the phiosphatase to phosphorylase a to prevent the premature activation of glycogen synthase |
|
|
Term
| depiction of how glucose regulates liver-glycogen metabolism |
|
Definition
|
|
