energy sources in muscle

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Energy sources inEnergy sources in

musclemuscleDr. Mummedy SwamyDr. Mummedy Swamy

Dept of Chemical pathologyDept of Chemical pathologyPPSP, USMPPSP, USM


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Lecture topicsLecture topics

Energy sources in muscleEnergy sources in muscle

Energy sources for muscleEnergy sources for muscle Metabolic pathways providing acetylMetabolic pathways providing acetyl--CoACoA

Metabolic pathways of energy production in muscleMetabolic pathways of energy production in muscle Metabolic pathways utilizing acetylMetabolic pathways utilizing acetyl--CoACoA

Citric acid cycleCitric acid cycle

Amino acid catabolismAmino acid catabolism

OxidativeOxidative phosphorylationphosphorylation

Electron trans port chainElectron trans port chain

OxidativeOxidative phosphorylationphosphorylation


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Lecture contentsLecture contents

Introduction to muscle energy metabolismIntroduction to muscle energy metabolism

Sources of energy for muscle contractionSources of energy for muscle contraction Metabolic pathways producing acetylMetabolic pathways producing acetyl--CoACoA

Carbohydrate metabolismCarbohydrate metabolism

GlycogenolysisGlycogenolysis

Anaerobic and aerobicAnaerobic and aerobic glycolysisglycolysis

PyruvatePyruvate dehydrogenasedehydrogenase reactionreaction

Lipid metabolismLipid metabolism --oxidationoxidation

KetoneKetone bodies metabolismbodies metabolism

KetolysisKetolysis


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IntroductionIntroduction

Muscle is the major transducer of chemical energy intoMuscle is the major transducer of chemical energy intomechanical energymechanical energy

The hydrolysis of ATP is used to drive movement of theThe hydrolysis of ATP is used to drive movement of thefilamentsfilaments

ATP in muscle is regenerated from ADP by:ATP in muscle is regenerated from ADP by: Anaerobic or aerobic catabolic processesAnaerobic or aerobic catabolic processes Substrate levelSubstrate level phsporylationphsporylation and oxidativeand oxidative phosphorylationphosphorylation

Skeletal muscle containsSkeletal muscle contains Fast (white, anaerobic) twitch fibersFast (white, anaerobic) twitch fibers Slow (red, aerobic) twitch fibersSlow (red, aerobic) twitch fibers

Skeletal muscle containSkeletal muscle contain myoglobinmyoglobin as a reservoir ofas a reservoir of

oxygenoxygen


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CreatineCreatinephosphatephosphate

CreatineCreatine phosphate is readily available highphosphate is readily available high--energyenergyphosphate in musclephosphate in muscle

It prevents the rapid depletion of ATPIt prevents the rapid depletion of ATP

ATP is generated from ADP by substrate levelATP is generated from ADP by substrate levelphosporylationphosporylation

The reaction is catalyzed byThe reaction is catalyzed by CreatineCreatine phosphokinasephosphokinase(CK)(CK)

CreatineCreatine phosphate + ADPphosphate + ADP CreatineCreatine + ATP+ ATP

Same enzyme is used forSame enzyme is used for creatinecreatine phosphate formationphosphate formationfrom ATP at times when the muscle is relaxed demandsfrom ATP at times when the muscle is relaxed demands

for ATP is not so greatfor ATP is not so great

CK


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Biosynthesis ofBiosynthesis of creatinecreatine andand creatininecreatinine

Amino acids used in the biosynthesisAmino acids used in the biosynthesis

glycineglycine,, argininearginine, and, and methioninemethionine

Enzymes1. Arginine-glycine

transamidinase (kidney)2. Guanidoacetate

methyltransferase (liver)3. Creatine phosphokinase

(muscle)

Creatinine is formed non-enzymatically1. The 24-hour excretion of

creatinine in the urine is

remarkably constant2. It is proportionate to muscle

mass


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ADPADP

AdenylateAdenylate kinasekinase oror myokinasemyokinase reactionreaction

2 ADP AMP + ATP2 ADP AMP + ATP

The above reaction is driven to right in the presence ofThe above reaction is driven to right in the presence of

AMPAMP deaminasedeaminase or 5or 5nucleotidasenucleotidase

AMP IMP + NHAMP IMP + NH33

AMP Adenosine + PiAMP Adenosine + Pi

Adenosine increases blood supply to muscleAdenosine increases blood supply to muscle IMP can be converted back to AMP in the presence ofIMP can be converted back to AMP in the presence of

aspartateaspartate ((purinepurine nucleotide cycle)nucleotide cycle)

IMP + AspIMP + Asp AdenylsuccinateAdenylsuccinate AMP +AMP + FumatateFumatate


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Metabolic pathwaysMetabolic pathways

Anaerobic pathwaysAnaerobic pathways

GlycolysisGlycolysis CreatinineCreatinine kinasekinase reactionreaction

AdenylateAdenylate kinasekinase reactionreaction

Aerobic pathwaysAerobic pathways

GlycolysisGlycolysis PDC reactionPDC reaction

--OxidationOxidation

KetolysisKetolysis Oxidation of amino acidOxidation of amino acid

carbon skeletoncarbon skeleton

Citric acid cycleCitric acid cycle

OxidativeOxidative

phosphorylationphosphorylation


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GlycogenGlycogen

Muscle contain large amounts of glycogenMuscle contain large amounts of glycogen

The release of glucose from glycogen is dependent on aThe release of glucose from glycogen is dependent on aspecific musclespecific muscleglycogenglycogenphosphorylasephosphorylase

CaCa2+2+, epinephrine, and AMP can activate the above, epinephrine, and AMP can activate the above

enzymeenzyme


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ContCont

GlycogenolysisGlycogenolysis::

Breakdown of muscle glycogenBreakdown of muscle glycogen Enzymes involved:Enzymes involved:

GlcogenGlcogen phosphorylasephosphorylase

DebranchingDebranchingenzymeenzyme PhosphoglucomutasePhosphoglucomutase

Glycogen + Pi GucoseGlycogen + Pi Gucose--11--PP

GlucoseGlucose--11--P GlucoseP Glucose--66--PP

Muscle does not contain glucoseMuscle does not contain glucose--66--

phosphatasephosphatase


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GlycolysisGlycolysis

It can occur in anaerobic & aerobic conditionsIt can occur in anaerobic & aerobic conditions

Mainly in white (fast twitch) fibers, anaerobicMainly in white (fast twitch) fibers, anaerobic

glycolysisglycolysis occursoccurs

Glucose 2 Lactate + 2 ATPGlucose 2 Lactate + 2 ATP

The Cori cycle

Excessively producedmuscle lactate isconverted to glucoseby gluconeogenisis inliver and released in

to circulation to beused by muscle


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ContCont

AerobicAerobic glycolysisglycolysis: It occurs red (slow twitch) fibers,: It occurs red (slow twitch) fibers,

Glucose 2Glucose 2 PyruvatePyruvate + 2 ATP + 2 NADH+ 2 ATP + 2 NADH In aerobic conditionsIn aerobic conditions pyruvatepyruvate is converted tois converted to

acetylacetyl--CoACoA by PDH enzyme complex (PDC)by PDH enzyme complex (PDC)

AcetylAcetyl--CoACoA entersentersTCA cycleTCA cycle & completely oxidized& completely oxidizedto carbon dioxideto carbon dioxide

Reduced coenzymes produced inReduced coenzymes produced in glycolysisglycolysis and TCAand TCAcycle enters ETC and produce ATP by oxidativecycle enters ETC and produce ATP by oxidative

phosphorylationphosphorylation


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Reactions ofReactions of glycolysisglycolysis


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Reactions of glycolysis:


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Reactions of glycolysis:


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ContCont

In anaerobic conditionsIn anaerobic conditions pyruvatepyruvate is converted to lactateis converted to lactate

by lactateby lactate dehydrogenasedehydrogenase (LDH)(LDH)

PyruvatePyruvate + NADH Lactate +NAD+ NADH Lactate +NAD

In aerobic conditionsIn aerobic conditions pyruvatepyruvate is converted to acetylis converted to acetyl--CoACoA byby pyruvatepyruvate dehydrogenasedehydrogenase complex (PDH /complex (PDH /PDC)PDC)

PyruvatePyruvate + NAD ++ NAD + CoACoA AcetylAcetyl--CoACoA +NADH + CO+NADH + CO22

AcetylAcetyl--CoACoA enters the TCA cycle and degraded toenters the TCA cycle and degraded tocarbon dioxidecarbon dioxide

LDH

PDC


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EnergeticsEnergetics ofof glycolysisglycolysis

Energy usedEnergy usedglucose + ATP glucoseglucose + ATP glucose--66--PP

fructosefructose--66--P + ATP fructoseP + ATP fructose--1, 61, 6-- bisbis PP

Energy producedEnergy produced

glyceraldehydeglyceraldehyde--33--P + NAD 1,3P + NAD 1,3--bisbis phophoglyceratephophoglycerate + NADH+ NADH

1,31,3--bisbis phosphoglyceratephosphoglycerate + ADP 3+ ADP 3--phosphoglycerate + ATPphosphoglycerate + ATP

PhosphoenolPhosphoenol pyruvatepyruvate + ADP+ ADP pyruvatepyruvate + ATP+ ATP

Hexokinase

Phospho-

fructokinase

Glyc-3-P

dehydrogenase

Phosphoglycerate

kinase

Pyruvate kinase


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PyruvatePyruvate dehydrogenasedehydrogenase reactionreaction

PyruvatePyruvate + NAD ++ NAD + CoACoAAcetylAcetyl--CoACoA + NADH + CO+ NADH + CO22

The oxidation of pyruvate to acetyl-CoA is the irreversible route from

glycolysis to citric acid cycle Pyruvate is oxidativelydecarboxilated to acetyl-CoA

Pyruvate dehydrogenase complex (amultienzyme complex) catalyses thisreaction


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Fatty acid transport into mitochondriaFatty acid transport into mitochondria

Long chain fatty acids penetrate the innerLong chain fatty acids penetrate the innermitochondrial membrane asmitochondrial membrane as carnitinecarnitine derivativesderivatives


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Reactions ofReactions of --OxidationOxidation

The reactions proceed in a cyclic form

Two carbons at a time are cleaved from acyl-CoA, starting from

carboxyl end

One cycle of -oxidation produces:Acetyl-CoA, acyl-CoA (2 carbon shorter than original fatty acid), NADH,

FADH2

Enzymes involved in -oxidation:

1. Acyl-CoA dehydrogenase2. Enoyl-CoA hydratase

3. Hydroxyacyl- CoA dehydrogenase

4. Thiolase


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EnergeticsEnergetics ofof --oxidationoxidation

Energy using reaction:Energy using reaction: Activation of fatty acid to fattyActivation of fatty acid to fatty acylacyl--CoACoA

Fatty acid +ATP +Fatty acid +ATP + CoACoA AcylAcyl--CoACoA ++ PpiPpi + AMP+ AMP

Energy producing reactions:Energy producing reactions: Oxidation ofOxidation of acylacyl--CoACoA byby acylacyl--CoACoA dehydrogenasedehydrogenase

acylacyl--CoACoA + FAD+ FAD enoylenoyl--CoACoA + FADH+ FADH22

Oxidation ofOxidation of --HydroxyacylHydroxyacyl--CoACoA byby dehydrogenasedehydrogenase

--HydroxyacylHydroxyacyl--CoACoA + NAD+ NAD --ketoacylketoacyl--CoACoA + NADH+ NADH


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energy sources in muscle

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