z 6 REVIEW KELOMPOK 5 6 Lipid metabolism summ ok.pptx
Transcript of z 6 REVIEW KELOMPOK 5 6 Lipid metabolism summ ok.pptx
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Lipid metabolism
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Lipid biological importance1. Fats & oils storage lipids2. Phospholipids & sterols structural lipids
3. Others
i. Cofactors
ii. Electron carriers
iii. Light-absorbing pigments
i. !"drophobic anchors for proteins
. #chaperone$ to help membrane protein fold
i. Emulsif"ing agents in digestie tract
ii. !ormones
iii. %ntracellular messenger
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"pes of '
( )imple triac"lgl"cerols* onl"one +ind of
fatt" acids ,eample*1*/tristearin0( ied triac"lgl"cerol
,mostl"0* 2 or moredierent fatt" acids.
( riac"lgl"cerols nonpolar
( Lipidsloer speci4c grait"
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Functions of Bile Salts
( They lower surface tension
,emulsify fats ,a pre requisite forthe action of pancreatic lipase
( he" actiate Lipase.
( he" shift the p! from 5 to ( he" form micelles ith fatt" acid6a
mono6di6trigl"ceride and help in
absorption( Promote absorption of fat soluble
itamins
( 7ile salts +eep cholesterol in soluble
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Metabolism of Fatty Acids and Triacylglycerols
Mobilization of Fatty Acids fromAdipocytes
When the energy supply from diet islimited, the body responds to thisdeciency through hormonal signals
transmitted to the adipose tissue byrelease of glucagon, epinephrine, oradrenocorticotropic hormone!
The hormones bind to the plasma
membranes of adipocyte cells andstimulate synthesis of cyclicAM"#cAM"$! The cAM" acti%ates a protein&inase that phosphorylates and inturn acti%ates hormone'sensiti%e
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These lipases hydrolyze thetriacylglycerols at position ) or * toproduce diacylglycerols #+A$ andfatty acid, which is the rate limitingstep in the hydrolysis! Thediacylglycerol lipases hydrolyze the+A to monoacylglycerols #MA$
and a fatty acid! Finally MA lipaseshydrolyze MA to fatty acid andglycerol!
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he free fatt" acids ,FF80 produced b" lipol"sismoe through the plasma membranes of theadipose cells and endothelial cells of bloodcapillaries b" simple diusion and bind to albuminin the blood plasma6 hich are transported toperipheral tissues.
he gl"cerol produced is ta+en up b" lier6phosphor"lated and oidi9ed to dih"dro"acetonephosphate6 hich is isomerised togl"ceraldeh"des-3-phosphate6 an intermediate ofboth gl"col"sis and gluconeogenesis.
herefore6 the gl"cerol is either conerted toglucose ,gluconeogenesis0 or to p"ruate,gl"col"sis0.
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Transport of Fatty Acids to theMitochondria
1. )peci4c for short chain ac"lgroups6 does not re:uire carnitine
2. )peci4c for the long chain ac"l
groups. he shuttles for long chainac"l groups are carnitineac"ltransferase % and %%. herefore6
long chain ac"l groups cross themitochondrial membrane incombination ith carnitine.
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;'o-idation of Fatty Acids he successie oidatie remoal of to carbons in the form of acet"l
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Complete oidation of fatt" acid can be diided in to tostages.
8. Formation of acet"l Co8.
7. Oidation of acet"l Co8 to CO26 ater ia C8 c"cle.
)tochiometr" of the reaction* Palmito"l Co8 = >F8? = > @8? =>Co8 A B 8cet"l
Co8=>F8?!2 => @8?!!.
Energetics of palmitate oidation*
educed e:uialent and produce energ" rich phosphatebonds. 8cet"l Co8 release energ" through C8 c"cle.
> F8?!2 D > 2 A 1 8Ps
>@8?!! D > 3 A 21 8Ps
B 8cet"l Co8 D B 12 A 5 8Ps
otal 8P produced from one molecule of palmitic acid is131. o 8Ps ,o energ" rich bonds0 are utili9ed6 duringactiation of fatt" acid. herefore total gain of 8Ps is 125.
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7iosintesis +eton
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6tilization of 7etone Bodiesetone bodies are produced in the Lier and the"
are utili9ed in etrahepatic tissues. Lier does notcontain the en9"me re:uired for actiation of
+etone bodies8ceto acetate is actiated b" to processes for
its utili9ation.
1. 8ceto acetate = 8P = Co8 D 8cetoacet"l Co8= 8P. he en9"me is )"nthethase
2. 8ceteo acetate = )uccin"l Co8 D 8ceto acet"lCo8 = )uccinate. he en9"me is
hiophorase,8bsent in Lier0
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8ceto acet"l Co8 is bro+en don to to molecules of 8cet"lCo86 hich enters C8 c"cle for the production of energ".
8ceto acetate and ;-h"dro" but"rate are the normalsubstrates for respiration and important sources ofenerg" .enal corte and heart muscle use acetoacetate in
preference to glucose .7rain sitches oer to utili9ation of +etone bodies for
energ" during staration and in uncontrolled diabetes.
8cetone is ehaled out .%t does not produce energ". @ormalleel of +etone bodies in blood is 1mg G.%n +etonemia6 the
leel increases. Ecretion of +etone bodies increases inurine6 called +etonuria.
%f the patient suers from both the signs6 it is called +etosis.
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2auses of 7etosis8 1. Prolonged staration6 depletion of carboh"drate stores
results in increased fatt" acid oidation and +etosis.
2. Lactating mothers deelop +etosis6 if the carboh"dratedemands are not met ith.
3. ?iabetic patients ith uncontrolled blood glucose6inariabl" suer from +etosis6 +etoacidosis.
etosis usuall" associated ith sustained high leels of
free fatt" acids in blood. Lipol"sis and +etogenesis are regulated b" hormones
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Biosynthesis of2holesterol
Hstep!' Co8 reductase
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2atabolism of 2holesterol8%ntestinal 7acteria conerts cholesterol to
coprostanol hich is ecreted in feces.Cholesterol brea+s don to cholic acid and
chenodeo"cholic acid.7oth are bile acids.he"combine ith sodium6 Potassium to form bilesalts.
he +e" en9"me I-h"dro"lase is inhibited b"
high concentration of bile acids.
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etabolicinterrelationships
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Three ma9or sources of metabolic fuelin our diets
Fie energ" conersion processes*
1. Carboh"drate metabolism,gl"col"sis and gluconeogenesis0
2. Lipid metabolism ,fatt" acidoidation & s"nthesis0
3. 8mino acid metabolism
,oidation and s"nthesis0
. Citrate c"cle
H. Oidatie phosphor"lation.
Lier cells can perform all ofs"nthesis and degradation reactions
ost other cell t"pes are primaril"limited to cataboli9ing glucose andfatt" acids to generate 8P throughmitochondrial oidatiephosphor"lation reactions.
ac rgan as a n :ue e a o c
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ac rgan as a n :ue e a o cPro4le
etabolic patterns of brain6 muscle6 adipose tissue6 +idne"6and lier are er" dierent.
7rain* - use glucose as a sole fuel in a ell-fed person
- use +etone bodies ,acetoacetate and 3-h"dro"but"rate0 during staration.
8dipose tissue is speciali9ed for s"nthesis6 storage6 andmobili9ation of triac"lgl"cerols.
idne" produces urine and reabsorbs glucose.
Lier* can rapidl" mobili9e gl"cogen and carr" out
gluconeogenesis to meet glucose needs of other organs.
pla"s a central role in the regulation of lipid metabolism.
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Lier functions *
determine what dietary nutrients :
metabolic fuels are distributed toperipheral
as a physiological glucose regulatorthat helps8 remo%e e-cess glucose from blood when
carbohydrate le%els are high releases glucose from stored glycogen, or
as a product of gluconeogenesis, when
serum glucose le%els are low! regulate serum glucose
through insulin : glucagon signaling pathways
modulate metabolic ;u- through glycolysis,
gluconeogenesis, and glycogen metabolism!
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-Phosphate
Lier retain dietar"monosaccharides in form of
glucose--phosphate'lucose--phosphate* has seeral fates depending on metabolic needs of lier and
peripheral tissues.
ost of it is used to s"nthesi9e lier gl"cogen.
%t can also be dephosphor"lated in lier
& released into blood to be used b"
other tissues6 in particular the brain.
%t is conerted to -phosphoglucolactone6 if lier need @8?P!
for bios"nthetic reactions6
%t can be conerted to fructose--phosphate & then
metaboli9ed b" gl"col"tic patha" and p"ruate
deh"drogenase reaction to "ield acet"l-Co8 for use in lipid
bios"nthesis6 oidatie phosphor"lation or +etogenesis.
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J)CLE* o t"pes of muscle tissue that pla" a
maKor role in metabolic integration*1. s+eletal muscle*
8mount of free fatt" acids6 glucose or +etone bodiesfor metabolic fuel is dierent 6 it is depending onph"sical moements re:uired ,rapid burst of actiit"or endurance actiit"0
primaril" uses fatt" acids released from adiposetissue as a source of energ".
fatt" acids are oidi9ed to generate acet"l-Co86 it isthen used b" citrate c"cle to produce reducingpoer ,@8?! and F8?!20 for oidatiephosphor"lation.
2. cardiac muscle* uses mostl" fatt" acids and +etone bodies as
metabolic fuel
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J)CLE*
When muscle contraction is required for a %eryshort burst of acti%ity, #ser%ing a tennis ball about
3'* seconds$, muscles use of intracellular AT" pool!
/f a more sustained le%el of muscle acti%ity isneeded, #*'< seconds$, then AT" pool is replenishedwith AT" from by a phosphoryl transfer reaction
using phosphocreatine
The creatine &inase reaction is readily re%ersible
: catalyzes resynthesis of phosphocreatine
when cellular AT" le%els return to normal
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J)CLE*
lycogen stores become depleted when
muscle contraction continues beyond aboutan hour!
As glucose le%els decline, to maintain highrates of AT" synthesis needed for
contraction, muscle tissue dependent on fatty acids released from adipose tissue &etone bodies produced in li%er
+uring long term star%ation, s&eletal musclecan be used as an energy source for bodyby pro%iding amino acid substrates for li%erand &idney gluconeogenesis!
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A+/"1S0 T/SS60
stores and releases fatty acids
from adipocytes #fat cells$ inresponse to metabolic needs!
secretes peptide hormonescalled adipo&ines #adipocytehormones$ that is used in
metabolic integration !
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o parts to triac"lgl"cerol c"cle)! Systemic component8
recycles fatty acids released from adipose tissue byhormone'sensiti%e lipase and triacylglycerolssynthesized in li%er cells
3! /ntracellular component8 recycles fatty acids that enter adipocytes following
triacylglycerol hydrolysis by lipoprotein lipase andtriacylglycerols synthesized inside adipocytes!
. 6nder normal conditions8 =5>? free fatty acids released by hormone'sensiti%e
lipase in adipocytes is returned to lipid droplets astriacylglycerols through either the systemic orintracellular routes!
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B@A/ requires as much as )3 grams of glucose each day
#C? of glucose used by our bodies under normal
conditions$!
is e-clusi%ely dependent on glucose under normalconditions to pro%ide AT" production!
Fatty acids cannot cross blood'brain barrier becausethey are bound to carrier proteins
7etone bodies #acetoacetate and +'.'hydro-ybutyrate$ are able to enter brain!
+emand for glucose to maintain brain function mustbe met by li%er!
+uring prolonged star%ation, #glucose le%els arelow$ brain adapts to using &etone bodies to supplyacetyl'2oA needed for AT" synthesis by o-idati%e
phosphorylation.
"rimary metabolic
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ypathways insi- ma9or tissues :organs
)! Di%er8 is control center of
metabolic networ& plays a crucial role in
regulating metabolite;u- between tissues :organs
e-port glucose :triacylglycerols toperipheral tissues!
3! Brain requires a constantinput of glucose
*! 2ardiac muscle use offatty acids and &etonebodies : glucose at a lowle%el!
4! Adipocyte tissue8e-change of fatty acids :triacylglycerols betweenli%er and adipocyte tissue
constitutes thetriacylglycerol cycle!
H. )+eletal muscle* uses glucose and fatt" acids deried from lier and dietar" sources for 8P s"nthesis
eports lactate bac+ to lier to complete Cori C"cle during times of prolonged ph"sical eertion.
%mportantl"6 the amino acids glutamine and alanine transport ecess nitrogen obtained from protein degradation in the muscle to the lier
and +idne" for ecretion as nitrogen aste in the form of urea.
. idne"* ecrete nitrogen aste ,form of urea0 from amino acids degradation
in lier
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%nsulin and glucagon are most important global metabolicregulators in humans
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Food /nta&e and Star%ation /nduceMetabolic 2hanges
/nsulin signals fed state8 /nsulin stimulates synthesis of glycogen and
triacylglycerols : proteins!
/ncreased secretion of insulin and decreased secretionof glucagon
glycogen is synthesized in muscle and li%er!
lucagon signals a low blood'glucose le%el8 lucagon stimulates glycogen brea&down and
gluconeogenesis by li%er : triacylglycerol hydrolysis byadipose tissue!
After a meal, rise in glucagon blood'glucose le%el leadsto
blood'glucose le%el drops degradation of glycogen and by gluconeogenic pathway
form glucose hydrolysis of triacylglycerols release fatty acids
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star%ation
Primar" metabolic challenge is to proide
enough glucose for brain to maintain normalneuronal cell functions.
7rain cannot use fatt" acids ,cannot cross
blood-brain barrier0.
ed blood cells are also dependent on serumglucose ,source of energ" to generate 8P0.
ature er"throc"tes lac+ mitochondria is notable to utili9e fatt" acids ,fatt" acid oidationta+es place in mitochondrial matri.0
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star%ation
lucose required at onset ofstar%ation #34 hour fast$8
)! +egradation of li%er glycogen #itis quic&ly depleted resulting in adrop in serum glucose le%els!
3! /ncrease gluconeogenic pathwayin li%er and &idneys to generateglucose for brain anderythrocytes! #ma9or substrates8glycerol, alanine, glutamate, and
lactate! The glycerol comes fromtriacylglycerol hydrolysis inadipose tissue, whereas, alanineand lactate are produced bytransamination reactions andanaerobic respiration,respecti%ely, in muscle cells!lutamate, which is thepreferred gluconeogenicprecursor in &idney cells, is anabundant metabolite in the bloodthat is deaminated to generate E'&etoglutarate, a citrate cycleintermediate that gi%es rise tothe gluconeogenic intermediateo-aloacetate!
*! 6se fatty acids fromtriacylglycerol hydrolysis in theadipose tissue as the primary
t b lit b t K ti d i
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etabolite u beteen maKor tissues and organs inhuman bod" under staration
Once gl"cogen stores are depleted,4rst 2 hours06 adipose tissue and
s+eletal muscle are primar"sources of metabolic fuel duringstaration.
Fatt" acids released fromtriac"lgl"cerol h"drol"sis inadipose tissue are transported tos+eletal muscle and heart.
%n lier6 acet"l-Co8 is usedproduction of +etone bodies thatare an energ" source for heart andbrain during staration.
8mino acids deried from protein
degradation in s+eletal muscleproides necessar" carbon forgluconeogenesis in lier & +idne".
'lucose from gluconeogenesis isused b" brain and er"throc"tes foraerobic and anaerobic respiration6respectiel".
Four ma or a terat ons n meta o c u- n
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order to sur%i%e long periods of time withoutfood8
10 %ncreased triac"lgl"cerol h"drol"sis in adipose tissue.
20 %ncreased gluconeogenesis in lier and +idne" cells.30 %ncreased +etogenesis in lier cells.
high rates of fatt" acid oidation6 and decreased ofoaloacetate for gluconeogenesis
acet"l-Co8 leels in lier increase dramaticall"
high leels of +etogenesis hich produces acetoacetateand ?-;-h"dro"but"rate for eport to other tissues.
brain and heart can use signi4cant amounts of +etone
bodies as a source of acet"l-Co8 for aerobic respiration. er"throc"tes are totall" dependent on glucose for
gl"col"sis because the" lac+ mitochondria hich arere:uired to oidi9e acet"l-Co8 b" the citrate c"cle.
0 Protein degradation in s+eletal muscle tissue. Once protein stores fall belo H/G of pre-staration
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)ources of blood glucose in fed6fasting6 and stared states.
From uderman @76 et al.%n* !anson M6 ehlman 86 eds.'luconeogenesis* %ts egulation inammalian )pecies. 15>*H1B.N 15> ohn Mile" & )ons
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Fuel 2hoice +uring 0-ercise /s +eterminedby /ntensity and +uration of Acti%ity
1//-meter sprint use stored 8P6creatine phosphate6 and anaerobicgl"col"sis to produce energ".
%n marathon6 the energ" fromoidation of both muscle gl"cogen
and fatt" acids deried from adiposetissue ,a highl" aerobic process0.
0th l Alt 0 M t b li
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0thanol Alters 0nergy Metabolismin the Di%er
Ethanol consumption leads to an accumulation of @8?!
1. %nhibits
gluconeogenesisb" preentingoidation of lactate to p"ruate.
lactate ill be
2. inhibits fatt" acid
oidation.Ecess @8?! leadto fatt" acids"nthesis.
riac"lgl"cerolsaccumulate in lier