gluconeo glycogen metabolism

8/8/2019 Gluconeo Glycogen Metabolism

1/17

www.Examville.com

Online practice tests, live classes, tutoring, study guides

Q&A, premium content and more.


2/17

GLYCOGEN METABOLISMGLYCOGEN METABOLISM

GLUCONEOGENESISGLUCONEOGENESIS


3/17


synthesis of glucose from noncarbohydratesynthesis of glucose from noncarbohydrateprecursors during longer periods ofprecursors during longer periods ofstarvationstarvation

a very important pathway since the braina very important pathway since the brain

depends on glucose as its primary fueldepends on glucose as its primary fuel((120g of120g of the 160g daily need for glucosethe 160g daily need for glucose))and RBCs use onlyand RBCs use only glucose as fuelglucose as fuel

amount of glucose in body fluids is 20g andamount of glucose in body fluids is 20g andthethe amount that can be derived fromamount that can be derived fromglycogen isglycogen is 190g190g

major noncarbohydrate sources aremajor noncarbohydrate sources are lactatelactate,,

amino acidsamino acids, and, and glycerolglycerol


4/17

noncarbohydrate sources need to be firstnoncarbohydrate sources need to be firstconverted to eitherconverted to either

pyruvatepyruvate,,oxaloacetateoxaloacetate oror

dihydroxyacetone phosphate (DHAP)dihydroxyacetone phosphate (DHAP)

to be converted to glucoseto be converted to glucose

major site is themajor site is the liverliverwith small amountwith small amount takingtakingplace in theplace in the kidneyskidneys

gluconeogenesis in the liver and kidneysgluconeogenesis in the liver and kidneys helpshelpsmaintain the glucose demands ofmaintain the glucose demands of the brain andthe brain andmuscles by increasingmuscles by increasing blood glucose levelsblood glucose levels

little occurs in the brain, skeletal musclelittle occurs in the brain, skeletal muscle ororheart muscleheart muscle

not a reversal of glycolysisnot a reversal of glycolysis


5/17

NONCARBOHYDRATE SOURCESNONCARBOHYDRATE SOURCES PyruvatePyruvate is converted to glucose in theis converted to glucose in the

gluconeogenetic pathwaygluconeogenetic pathway

LactateLactate is formed byis formed by active skeletal muscleactive skeletal muscle whenwhenglycolytic rate exceeds oxidative rate; becomesglycolytic rate exceeds oxidative rate; becomesglucose by first converting it toglucose by first converting it to pyruvatepyruvate

Amino acidsAmino acids are derived fromare derived from dietary proteinsdietary proteins andandinternal protein breakdowninternal protein breakdown during starvationduring starvation;;becomes glucose by converting them first to eitherbecomes glucose by converting them first to either

pyruvate or oxaloacetatepyruvate or oxaloacetate

GlycerolGlycerol is derived from theis derived from the hydrolysis ofhydrolysis oftriacylglycerols (TAG) or triglyceridestriacylglycerols (TAG) or triglycerides; becomes; becomesglucose by conversion first toglucose by conversion first to dihydroxyacetonedihydroxyacetone

phosphate (DHAP)phosphate (DHAP)


6/17

IRREVERSIBLE STEPS ofGLYCOLYSISIRREVERSIBLE STEPS ofGLYCOLYSIS

Causes of most of the decrease in free energyCauses of most of the decrease in free energy

in glycolysisin glycolysis

Bypassed steps during gluconeogenesisBypassed steps during gluconeogenesis

Steps catalyzed by the enzymesSteps catalyzed by the enzymes

HexokinaseHexokinase

((glucose + ATPglucose + ATPGG--66--P + ADPP + ADP))

PhosphofructokinasePhosphofructokinase

((FF--66--P + ATPP + ATPFF--1,61,6--BP + ADPBP + ADP))

Pyruvate kinasePyruvate kinase

((PEP + ADPPEP + ADPPyruvate + ATPPyruvate + ATP))


7/17

NEW STEPS in GLUCOSE FORMATION from PYRUVATE viaNEW STEPS in GLUCOSE FORMATION from PYRUVATE via


PEP is formed from pyruvate by way ofPEP is formed from pyruvate by way ofoxaloacetateoxaloacetate PyruvatePyruvate + CO+ CO22 + ATP + HOH+ ATP + HOH ------------------------ oxaloacetateoxaloacetate + ADP + Pi + 2H+ ADP + Pi + 2H

++

OxaloacetateOxaloacetate + GTP+ GTP -------------------------- PEPPEP + GDP + CO+ GDP + CO22

FF--66--P is formed from FP is formed from F--1,61,6--BP by hydrolysis ofBP by hydrolysis ofthe phosphate ester at carbon 1, anthe phosphate ester at carbon 1, anexergonic hydrolysisexergonic hydrolysis

FructoseFructose--1,61,6--bisphosphatebisphosphate + HOH+ HOH ---------------------------- fructosefructose--66--phosphatephosphate + Pi+ Pi

Glucose is formed by hydrolysis ofGGlucose is formed by hydrolysis ofG--66--PP

GlucoseGlucose--66--phosphate + HOHphosphate + HOH -------------------------- glucose + Piglucose + Pi

Pyruvate carboxylase

PEP carboxykinase

Fructose-1,6-bisphosphatase

Glucose-6-phosphatase


8/17

RECIPROCAL REGULATION OF GLYCOLYSISRECIPROCAL REGULATION OF GLYCOLYSIS

& GLUCONEOGENESIS& GLUCONEOGENESIS

Glucose

Fructose-6-phosphate

Fructose-1,6-bisphosphate

PEP

Pyruvate

Oxaloacetate

PFK F-1,6-BPase

Several steps

PK

PEPcarboxykinase

Pyruvate

carboxylase

GLUCONEOGENESIS

F-2,6-BP +

AMP +

ATP -

Citrate -

H+ -

F-2,6-BP -

AMP -Citrate +

F-1,6-BP +

ATP -

Alanine -AcetylCoA +

ADP -

ADP -


9/17

GLYCOGENGLYCOGEN Readily mobilized storage form of glucoseReadily mobilized storage form of glucose

very large, branched polymer of glucosevery large, branched polymer of glucoseresidues linked viaresidues linked via --1,4 (straight) and1,4 (straight) and --1,6 glycosidic bonds1,6 glycosidic bonds

branching occurs for every 10branching occurs for every 10thth

glucoseglucoseresidue of the open helical polymerresidue of the open helical polymer

not as reduced as fatty acids are andnot as reduced as fatty acids are andconsequently not as energyconsequently not as energy--richrich

serves as buffer to maintain blood sugarserves as buffer to maintain blood sugarlevelslevels

Released glucose from glycogen can provideReleased glucose from glycogen can provide

energy anaerobically unlike fatty acidsenergy anaerobically unlike fatty acids


10/17

Two major sites of glycogen storage are theTwo major sites of glycogen storage are the

liver (10% by weight) and skeletal muscles (2%liver (10% by weight) and skeletal muscles (2%

by weight)by weight)

In the liver, its synthesis and degradation areIn the liver, its synthesis and degradation are

regulated to maintain normal blood glucoseregulated to maintain normal blood glucose

in the muscles, its synthesis and degradation isin the muscles, its synthesis and degradation is

intended to meet the energy needs of theintended to meet the energy needs of themuscle itselfmuscle itself

present in the cytosol as granules (10present in the cytosol as granules (10--40nm)40nm)


11/17

GLYCOGENOLYSISGLYCOGENOLYSIS

Consists of three stepsConsists of three steps1.1. release of glucoserelease of glucose--11--phosphate fromphosphate from

from the nonreducing ends offrom the nonreducing ends of

glycogenglycogen (phosphorolysis)(phosphorolysis)

2.2. remodeling of glycogen substrate toremodeling of glycogen substrate to

permit further degradation with a transferasepermit further degradation with a transferase

andand --1,61,6 glucosidaseglucosidase

3.3. conversion of glucoseconversion of glucose--11--phosphatephosphate

to glucoseto glucose--66--phosphate for furtherphosphate for further

metabolismmetabolism


12/17

Fates of GlucoseFates of Glucose--66--PhosphatePhosphate

Initial substrate forInitial substrate forglycolysisglycolysis

Can be processed by theCan be processed by the pentosepentose

phosphate pathwayphosphate pathway to NADPH andto NADPH andribose derivativesribose derivatives

Can beCan be converted to free glucoseconverted to free glucose in thein theliver, intestine and kidneys for release intoliver, intestine and kidneys for release into

the blood streamthe blood stream


13/17

GlycogenGlycogen

GlycogenGlycogen nn--11

GlucoseGlucose--11--phosphatephosphate

GlucoseGlucose--66--phosphatephosphate

GlycolysisGlycolysis PPPPPP

PyruvatePyruvate GlucoseGlucose Ribose +Ribose +

NADPHNADPHLactateLactate COCO22 + HOH+ HOH

Blood for use byBlood for use by

other tissuesother tissues

Muscle,Brain

Liver

Glycogen phosphorylase

Glucose-6-phosphatase

Phosphoglucomutase


14/17

GLYCOGENESISGLYCOGENESIS Regulated by a complex system and requires aRegulated by a complex system and requires a

primer,primer,glycogeninglycogenin

Requires anRequires an activated form of glucoseactivated form of glucose, the, the

Uridine diphosphate glucose (UDPUridine diphosphate glucose (UDP--

glucose) formed from UTP andglucose) formed from UTP and glucoseglucose--11--phosphatephosphate

UDPUDP--glucose is added to the nonreducingglucose is added to the nonreducing end ofend of

glycogenglycogen usingusing glycogen synthaseglycogen synthase, the key, the keyregulatory enzyme in glycogen synthesisregulatory enzyme in glycogen synthesis

Glycogen is then remodeledGlycogen is then remodeledfor continuedfor continued

synthesissynthesis


15/17

GLYCOGEN BREAKDOWN & SYNTHESIS AREGLYCOGEN BREAKDOWN & SYNTHESIS ARE

RECIPROCALLY REGULATEDRECIPROCALLY REGULATED

Glycogen breakdownGlycogen breakdown Glycogen synthesisGlycogen synthesisEpinephrine

Adenylate cyclase Adenylate cyclase

ATP cAMP

Protein kinase A Protein kinase A

Phosphorylase kinase Phosphorylase kinase

Phosphorylase b Phosphorylase a

Glycogen synthase a Glycogen synthase b

PINK inactive GREEN - active


16/17

GLYCOGEN STORAGE DISEASEGLYCOGEN STORAGE DISEASETYPETYPE DEFECTIVEDEFECTIVE

ENZYMEENZYMEORGAN AFFECTEDORGAN AFFECTED GLYCOGEN INGLYCOGEN IN

AFFECTED ORGANAFFECTED ORGANCLINICAL FEATURESCLINICAL FEATURES

I (Von Gierke)I (Von Gierke) GlucoseGlucose--66--phosphatasephosphatase

Liver & kidneyLiver & kidney Increased amount;Increased amount;normal structurenormal structure

Hepatomegaly, failure to thrive,Hepatomegaly, failure to thrive,hypoglycemia, ketosis,hypoglycemia, ketosis,hyperuricemia, hyperlipidemiahyperuricemia, hyperlipidemia

II (Pompe dse)II (Pompe dse) --1,4 glucosidase1,4 glucosidase All organsAll organs Massive increase inMassive increase inamount; normalamount; normalstructurestructure

Cardiorespiratory failure causesCardiorespiratory failure causesdeath usually before age 2death usually before age 2

III (Cori dse)III (Cori dse) AmyloAmylo--1,61,6--glucosidaseglucosidase

(debranching)(debranching)

Muscle & liverMuscle & liver Increased amount;Increased amount;short outer branchesshort outer branches

Like type 1 but milderLike type 1 but milder

IV (AndersenIV (Andersendse)dse)

Branching enzymeBranching enzyme((--1,4 & 1,6)1,4 & 1,6)

Liver & spleenLiver & spleen Normal amount; veryNormal amount; verylong outer brancheslong outer branches

Progressive cirrhosis of the liver;Progressive cirrhosis of the liver;liver failure causes death beforeliver failure causes death beforeage 2age 2

V (McArdle dse)V (McArdle dse) PhosphorylasePhosphorylase musclemuscle ModeratelyModeratelyincreased amount;increased amount;normal structurenormal structure

Limited ability to performLimited ability to performstrenuous exercise because ofstrenuous exercise because ofpainful muscle cramps.painful muscle cramps.Otherwise patient is normal orOtherwise patient is normal or

wellwell--developed.developed.VI (Hers dse)VI (Hers dse) PhosphorylasePhosphorylase liver liver Increased amountIncreased amount Like type 1 but milderLike type 1 but milder

VIIVII PhosphofructokinaPhosphofructokinasese

musclemuscle Increased amount;Increased amount;normal structurenormal structure

Like type VLike type V

VIIIVIII PhosphorylasePhosphorylasekinasekinase

liverliver Increased amount;Increased amount;normal structurenormal structure

Mild liver enlargement. MildMild liver enlargement. Mildhypoglycemiahypoglycemia


17/17

Its FREE to join.

http://www.examville.com

gluconeo glycogen metabolism

Documents