Mbs127 Slide Glycogenesis

7/30/2019 Mbs127 Slide Glycogenesis

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GLYCOGENESISGLYCOGENESIS

Glycogen synthesis occurs after a meal, whenGlycogen synthesis occurs after a meal, when

blood glucose level are highblood glucose level are highGlycogen is stored in muscle and liver for quiteGlycogen is stored in muscle and liver for quitedifferent reasonsdifferent reasons

Muscle glycogen is a readily available source ofMuscle glycogen is a readily available source ofglucose for glycolysis within the muscle itselfglucose for glycolysis within the muscle itself

Liver glycogen functions to store and exportLiver glycogen functions to store and export

glucose to maintain blood glucose betweenglucose to maintain blood glucose betweenmealsmeals

Liver glycogen levels vary greatly in response toLiver glycogen levels vary greatly in response to

intake of foodintake of food


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Its accumulating to high levels shortly after a mealIts accumulating to high levels shortly after a meal

Then its decreasing slowly as it is mobilized to helpThen its decreasing slowly as it is mobilized to help

maintain a nearly constant blood glucose levelmaintain a nearly constant blood glucose level


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Glycogen synthesis from ofGlycogen synthesis from of D glucoseD glucose

The process occurs in theThe process occurs in the cytosolcytosol

The process requires energy supplied by ATPThe process requires energy supplied by ATPand Uridine triphosphate (UTP)and Uridine triphosphate (UTP)

Gl co enesis involves the followin set ofGl co enesis involves the followin set of

REACTIONS OF GLYCOGENESISREACTIONS OF GLYCOGENESIS

reactions :reactions :

-- Phosphorylation of glucose to form glucose 6Phosphorylation of glucose to form glucose 6phosphate byphosphate by hexokinasehexokinase oror glucokinaseglucokinase

-- Synthesis of glucose 1 phosphate bySynthesis of glucose 1 phosphate byphosphoglucomutasephosphoglucomutase from glucose 6 phosphatefrom glucose 6 phosphate

-- Synthesis of UDPSynthesis of UDP--glucose by action ofglucose by action of glucoseglucose

11--phosphate uridylyltransferasephosphate uridylyltransferase


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-- Synthesis of glycogen from UDPSynthesis of glycogen from UDP--glucoseglucoseThis process requires two enzymes:This process requires two enzymes:a.a. Glycogen SynthaseGlycogen Synthasecreates chains of glucose molecules withcreates chains of glucose molecules with

--


b.b. AmyloAmylo-- (1,4(1,41,6)1,6)--glucosyl transferaseglucosyl transferase(branching enzyme)(branching enzyme)removes a block of about seven glucosylremoves a block of about seven glucosyl

residues from a growing chain andresidues from a growing chain andtransfers it to another chain to produce antransfers it to another chain to produce an--1,61,6--glycosidicglycosidic


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GlycogenolysisGlycogenolysis


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Synthesis of Primer to InitiateSynthesis of Primer to InitiateGlycogen SynthesisGlycogen Synthesis

A primer is needed for glycogen synthesisA primer is needed for glycogen synthesis

Glycogen synthase cannot initiate chainsGlycogen synthase cannot initiate chainssynthesis using free glucose as an acceptor of asynthesis using free glucose as an acceptor of amolecule of glucose from UDPmolecule of glucose from UDP--glucoseglucose

A fragment of glycogen can serve as a primer inA fragment of glycogen can serve as a primer incells whose glycogen store are not totallycells whose glycogen store are not totallydepleteddepleted

In the absence of a glycogen fragment, aIn the absence of a glycogen fragment, aspesific protein, calledspesific protein, called glycogeninglycogenin can serve ascan serve asan acceptor of glucose residuesan acceptor of glucose residues


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Synthesis of Primer to InitiateSynthesis of Primer to InitiateGlycogen SynthesisGlycogen Synthesis

Glycogenin is now known that a polypeptide ofGlycogenin is now known that a polypeptide of332 amino acids332 amino acids

Transfer of the first molecule of glucose fromTransfer of the first molecule of glucose from--

glycogen initiator synthaseglycogen initiator synthase

Glycogenin itself can then transfer a fewGlycogenin itself can then transfer a fewadditional glucosyl units to the growingadditional glucosyl units to the growing --1,41,4

glucosyl chainglucosyl chainGlycogenin is aself glucosylating enzymeGlycogenin is aself glucosylating enzyme


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GLYCOGENOLYSISGLYCOGENOLYSIS

GlycogenolysisGlycogenolysis refers to breakdown of glycogenrefers to breakdown of glycogen

to glucose or glucose 6 phosphate in responseto glucose or glucose 6 phosphate in responseto low blood glucoseto low blood glucose

This process occurs in theThis process occurs in the cytosolcytosol

It is not a reversal of the synthetic reactionsIt is not a reversal of the synthetic reactions

In humans, the store of liver glycogen lastsIn humans, the store of liver glycogen lastssomewhere between 12 and 24 hour duringsomewhere between 12 and 24 hour during

fastingfasting


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Glycogen degradation requires the followingGlycogen degradation requires the following

reactions :reactions :Shortening of chainsShortening of chains-- Using inorganic phosphate (Pi),Using inorganic phosphate (Pi), glycogenglycogen

,,the outer branches of glycogenthe outer branches of glycogen-- Glycogen phosphorylase stops when it comesGlycogen phosphorylase stops when it comeswithin four glucose residus of branch pointwithin four glucose residus of branch point

-- A glycogen molecule that has been degradedA glycogen molecule that has been degradedto its branch points is calledto its branch points is called a limit dextrina limit dextrin-- Phosphorylase cannot degrade it any furtherPhosphorylase cannot degrade it any further


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Removal of branchesRemoval of branches

-- OligoOligo--((--1,41,4 --1,4)1,4)--glucantransferaseglucantransferaseremoves the outer three of the four glucoseremoves the outer three of the four glucoseresidues attached at a branch and transfer themresidues attached at a branch and transfer them

-- It cause exposing the 1,6 branch pointIt cause exposing the 1,6 branch point

-- AmyloAmylo--(1,6)(1,6)--glucosidase (debranchingglucosidase (debranchingenzyme)enzyme), begins the removal of, begins the removal of (1,6)(1,6)

-- With the removal of the branch, further action byWith the removal of the branch, further action byphosphorylase can proceedphosphorylase can proceed


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Conversion of glucose 1 phosphate to glucose 6Conversion of glucose 1 phosphate to glucose 6

phosphatephosphate-- glucose 1 phosphate, produced by glycogenglucose 1 phosphate, produced by glycogenphosphorylase is converted to glucose 6phosphorylase is converted to glucose 6

-- It catalyzed byIt catalyzed by phosphoglucomutasephosphoglucomutase

-- In liver and kidney but not in muscle ,In liver and kidney but not in muscle , glucose 6glucose 6phosphatasephosphatase, removes phosphate from glucose 6, removes phosphate from glucose 6phosphatephosphate

-- It enabling glucose to beIt enabling glucose to be formed and diffuseformed and diffusefrom the cell into the bloodfrom the cell into the blood


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GlycogenolysisGlycogenolysis


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PATHWAY OF GLYCOGENESIS ANDPATHWAY OF GLYCOGENESIS ANDOF GLYCOGENOLYSISOF GLYCOGENOLYSIS


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GLYCOGEN STORAGE DISEASESGLYCOGEN STORAGE DISEASES

A group of genetic disease that result from aA group of genetic disease that result from a

defect in an enzyme required for either glycogendefect in an enzyme required for either glycogensynthesis or degradationsynthesis or degradation

The result in either formation of glycogen thatThe result in either formation of glycogen that

of excessive amounts of normal glycogen inof excessive amounts of normal glycogen inspecific tissuespecific tissue

A particular enzyme may be defective in a singleA particular enzyme may be defective in a single

tissuetissueThe severity of disease may range from fatalThe severity of disease may range from fatalinfancy to mild disorders that are not lifeinfancy to mild disorders that are not life

threateningthreatening


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Some of the more prevalent glycogen storageSome of the more prevalent glycogen storage

diseases :diseases :

Von Gierkes diseaseVon Gierkes disease

-- Called type I glycogen storage diseaseCalled type I glycogen storage disease

--


-- Affects liver, kidney and intestineAffects liver, kidney and intestine

-- Fasting hypoglycemiaFasting hypoglycemia--severesevere

-- Fatty liver, hepatomegalyFatty liver, hepatomegaly

-- Hyperlacticacidemia and hyperuricemiaHyperlacticacidemia and hyperuricemia

-- Normal glycogen structure, increased glycogenNormal glycogen structure, increased glycogenstoredstored


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Type I :Type I : Von Gierkes diseaseVon Gierkes disease


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Some of the more prevalent glycogen storageSome of the more prevalent glycogen storage

diseases :diseases :Pompes diseasePompes disease

-- Called type II glycogen storage diseaseCalled type II glycogen storage disease


-- InbornInborn lysosomal enzyme defectlysosomal enzyme defect-- Excessive glycogen concentrations found inExcessive glycogen concentrations found inabnormal vacuoles in the cytosolabnormal vacuoles in the cytosol

-- Normal blood sugar levelNormal blood sugar level-- Severe cardiomegalySevere cardiomegaly

-- Early death usually occursEarly death usually occurs


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Coris diseaseCoris disease-- Called type III glycogen storage diseaseCalled type III glycogen storage disease

-- Caused bCaused b deficienc ofdeficienc of l co en debrancherl co en debrancher

GLYCOGEN STRORAGE DISEASESGLYCOGEN STRORAGE DISEASES

enzymeenzyme-- Glycogen accumulates because only the outerGlycogen accumulates because only the outerbranches can be removed from the molecule bybranches can be removed from the molecule by

phosphorylasephosphorylase-- Hepatomegaly occurs, but diminishes with ageHepatomegaly occurs, but diminishes with age


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McArdles SyndromeMcArdles Syndrome

-- Called type V glycogen storage diseaseCalled type V glycogen storage disease-- Caused byCaused by skeletal muscle glycogenskeletal muscle glycogenphosphorylase deficiencyphosphorylase deficiency (liver enzyme normal)(liver enzyme normal)

GLYCOGEN STRORAGE DISEASESGLYCOGEN STRORAGE DISEASES

--muscle after exercisemuscle after exercise

-- No rise blood lactate during strenuous exerciseNo rise blood lactate during strenuous exercise

-- Normal mental developmentNormal mental development

-- Myoglobinuria in later lifeMyoglobinuria in later life

-- High level of glycogen with normal structure inHigh level of glycogen with normal structure inmusclemuscle


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Glycogen Storage DiseasesGlycogen Storage Diseases

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Mbs127 Slide Glycogenesis