Integration of metabolism with correlated diagrams.pdf

The metabolism of carbohydrates, lipids and proteins are interrelated and occur simultaneously. This integration of metabolism must be considered at two levels: cellular level and tissue or organ level. Integration of metabolism at cellular level includes the flow of key metabolites, e.g. glucose, fatty acids and amino acids, between different metabolic pathways at the cellular level. Integration of metabolism at tissue or organ level includes the inter-relationship of different tissues and organs in maintaining an appropriate metabolic state for the whole body. Integration of metabolism ensures a supply of suitable fuel for all the tissues, at all times from the fully fed state to the totally starved state. Starvation is the deprivation of the food and thereby the energy demands of the body for basal metabolism and other activities. Starvation can be divided into two phases characterized by distinct metabolic patterns: short term starvation and prolonged starvation. Short starvation covers the 12 hours overnight fast and can extend to 24 hours. Prolonged starvation lasts longer than 24 hours and can extend into several days or weeks.
Integration of metabolism is essential on both short-term and long-term bases. Perhaps the most
crucial short-term element is maintenance of a stable blood glucose level. The table below has
been presented earlier but I will use it here to emphasize the fact that exercise can quickly reduce
blood sugar levels. Maintenance of blood glucose levels over 2.5-3 mmol/l is essential for brain
function. One might expect, therefore, that nature had equipped us with a sizable glucose
reserve. Surprisingly, the total amount of glucose in the blood and liver is so small that it can be
exhausted in minutes. The same result, a rapid reduction of blood glucose levels and ensuing
loss of consciousness, follows administration of large doses of insulin (insulin-shock therapy).
Stated more clearly, the body's metabolic balance can quickly be disrupted through excessive
activity or hormonal derangement. And yet, this does not normally occur. Physiological
processes adjust carbohydrate and fat metabolism such that blood glucose values do not fall
markedly. If we have a shortage of sugar, fat metabolism takes over. Integration of metabolism
protects us against metabolic catastrophes!
Integration of metabolism is important on a long-term basis too. Blood sugar, glucose, is not an
"inert and gentle" component of our diet. Glucose is toxic! Chronic high blood levels of glucose
lead to protein denaturing and the development of blindness, neuropathy and the kidney damage
seen in diabetes. High blood sugar levels lead to increased circulating triglycerides and are
responsible for development of cardiovascular disease. Again, integration of metabolism and
control by hormones and metabolites normally prevent these adverse effects of sugar. Let us
look at the integration process.
uptake from the circulation.
For further info.

1. Integration of Metabolism
Integrated CIRCUIT or IC of Metabolism
The breakdown and synthesis
ofcarbohydrates,proteins,andlipids
connectwiththepathwaysof
glucosecatabolism.Thesimplesugarsare
galactose,fructose,glycogen,andpentose....
Theaminoacidsfromproteinsconnectwith
glucosecatabolismthroughpyruvate,acetyl
CoA,andcomponentsoftheTCAcycle.
HowdoessandwichendupasATPin
ourbodycells?Thishappensbecauseallof
thecatabolicpathwaysforcarbohydrates,
proteins,andlipidseventuallyconnectinto
glycolysisandthecitricacidcyclepathways
(seeFigure).Metabolicpathwaysshouldbe
thoughtofasporous—thatis,substances
enterfromotherpathways,andintermediates
leaveforotherpathways.Thesepathways
arenotclosedsystems.Manyofthe
substrates,intermediates,andproductsina
particularpathwayarereactantsinother
pathways.It’sreallylooksoneIC.

2. Integration of Metabolism
Sugar
metabolism
Lipid
metabolism
Amino acid
metabolism
Amino acid
metabolism
Nucleotide
metabolism

3. Any energy nutrient can fuel the body in the short term
TCA cycle = amphibolicpathway
Lipogenesis
•CHO spares lipolysis-promotes gain
•Glucose is precursor for glycerol & fatty acids
Gluconeogenesis
•Glycerol portion only from fat
•Fatty acids with odd # of C atoms
•Glucogenicamino acids
Conversion among energy nutrients favors lipogenesis
TCA cycle & electron transport chain -common to all 3
This catabolic pathway also:
•Produces CO
2for carboxylation& C for other needs
•Provides common intermediates
•Provides citrate & malatefor lipogenesis

4. Connections of Other Sugars to Glucose Metabolism
Glycogen,apolymerofglucose,isanenergystoragemoleculein
animals.WhenthereisadequateATPpresent,excessglucoseis
shuntedintoglycogenforstorage.Glycogenismadeandstoredin
bothliverandmuscle.Theglycogenwillbehydrolyzedintoglucose
monomers(G-1-P)ifbloodsugarlevelsdrop.Thepresenceof
glycogenasasourceofglucoseallowsATPtobeproducedfora
longerperiodoftimeduringexercise.Glycogenisbrokendowninto
G-1-PandconvertedintoG-6-Pinbothmuscleandlivercells,and
thisproductenterstheglycolyticpathway.
Sucroseisadisaccharidewithamoleculeofglucoseanda
moleculeoffructosebondedtogetherwithaglycosidiclinkage.
Fructoseisoneofthethreedietarymonosaccharides,alongwith
glucoseandgalactose(whichispartofthemilksugar,the
disaccharidelactose),whichareabsorbeddirectlyintothe
bloodstreamduringdigestion.Thecatabolismofbothfructoseand
galactoseproducesthesamenumberofATPmoleculesasglucose.

5. EVERY STEP of REACTIONS in OUR BODY -CELL is DONE by an ENZYME
& MOST BIOCHEMICAL ACTIVITIES are CHAIN -REACTIONS

6. Connections of Proteins to Glucose Metabolism
Proteinsarehydrolyzedbyavarietyofenzymesincells.Mostof
thetime,theaminoacidsarerecycledintothesynthesisofnew
proteins.Ifthereareexcessaminoacids,however,orifthebody
isinastateofstarvation,someaminoacidswillbeshuntedinto
thepathwaysofglucosecatabolism(Figure7.6.17.6.1).Each
aminoacidmusthaveitsaminogroupremovedpriortoentry
intothesepathways.Theaminogroupisconvertedinto
ammonia.Inmammals,theliversynthesizesureafromtwo
ammoniamoleculesandacarbondioxidemolecule.Thus,urea
istheprincipalwasteproductinmammalsproducedfromthe
nitrogenoriginatinginaminoacids,anditleavesthebodyin
urine.

7. Connecting Proteins to Glucose Metabolism
Excess amino acids are converted into molecules that can enter the pathways of
glucose catabolism.
Amino acids must be deaminatedbefore entering any of the pathways of
glucose catabolism: the amino group is converted to ammonia, which is used by
the liver in the synthesis of urea.
Deaminatedamino acids can be converted into pyruvate, acetyl CoA, or some
components of the citric acid cycle to enter the pathways of glucose catabolism.
Several amino acids can enter the glucose catabolism pathways at multiple
locations.
Connection of Amino Acids to Glucose Metabolism Pathways:
Thecarbonskeletonsofcertainaminoacids(indicatedinboxes)arederivedfrom
proteinsandcanfeedintopyruvate,acetylCoA,andthecitricacidcycle.
•Whenbloodsugarlevelsdrop,glycogenisbrokendownintoglucose-1-
phosphate,whichisthenconvertedtoglucose-6-phosphateandentersglycolysis
forATPproduction.
•Intheliver,galactoseisconvertedtoglucose-6-phosphateinordertoenterthe
glycolyticpathway.
•Fructoseisconvertedintoglycogenintheliverandthenfollowsthesamepathway
asglycogentoenterglycolysis.
Sucrose is broken down into glucose and fructose; glucose enters the pathway
directly while fructose is converted to glycogen.

8. Metabolic Interrelationships

9. Connecting Lipids to Glucose Metabolism
Lipidscanbebothmadeandbrokendownthroughpartsoftheglucosecatabolism
pathways.Manytypesoflipidsexist,butcholesterolandtriglyceridesarethelipids
thatenterthepathwaysofglucosecatabolism.Throughtheprocessof
phosphorylation,glycerolcanbeconvertedtoglycerol-3-phosphateduringthe
glycolyticpathway.Whenfattyacidsarebrokendownintoacetylgroupsthroughbeta-
oxidation,theacetylgroupsareusedbyCoAtoformacetyl-CoA,whichentersthe
citricacidcycletoproduceATP.Beta-oxidationproducesFADH
2andNADH,whichare
usedbytheelectrontransportchainforATPproduction.
Cholesterol
Cholesterolcontributestocellmembraneflexibilityandisaprecursortosteroid
hormones.Thesynthesisofcholesterolstartswithacetylgroups,whicharetransferred
fromacetylCoA,andproceedsinonlyonedirection;theprocesscannotbereversed.
Thus,synthesisofcholesterolrequiresanintermediateofglucosemetabolism.
Triglycerides
Triglycerides,aformoflong-termenergystorageinanimals,aremadeofglyceroland
threefattyacids.Triglyceridescanbebothmadeandbrokendownthroughpartsof
theglucosecatabolismpathways.Glycerolcanbephosphorylatedtoglycerol-3-
phosphate,whichcontinuesthroughglycolysis.
Fattyacidsarecatabolizedinaprocesscalledbeta-oxidationthattakesplaceinthe
matrixofthemitochondriaandconvertstheirfattyacidchainsintotwocarbonunitsof
acetylgroups,whileproducingNADHandFADH
2.Theacetylgroupsarepickedupby
CoAtoformacetylCoAthatproceedsintothecitricacidcycleasitcombineswith
oxaloacetate.TheNADHandFADH
2arethenusedbytheelectrontransportchain.

10. Connections of Carbohydrate, Protein,
and Lipid Metabolic Pathways

11. Connections of Lipid and Glucose Metabolisms
Thelipidsthatareconnectedtotheglucosepathwaysare
cholesterolandtriglycerides.Cholesterolisalipidthatcontributes
tocellmembraneflexibilityandisaprecursorofsteroidhormones.
Thesynthesisofcholesterolstartswithacetylgroupsandproceeds
inonlyonedirection.Theprocesscannotbereversed.
Triglyceridesareaformoflong-termenergystorageinanimals.
Triglyceridesaremadeofglycerolandthreefattyacids.Animals
canmakemostofthefattyacidstheyneed.Triglyceridescanbe
bothmadeandbrokendownthroughpartsoftheglucose
catabolismpathways.Glycerolcanbephosphorylatedtoglycerol-
3-phosphate,whichcontinuesthroughglycolysis.Fattyacidsare
catabolizedinaprocesscalledbeta-oxidationthattakesplacein
thematrixofthemitochondriaandconvertstheirfattyacidchains
intotwocarbonunitsofacetylgroups.Theacetylgroupsare
pickedupbyCoAtoformacetylCoAthatproceedsintothecitric
acidcycle.

13. 2 20
2+ 4H
+
+ 4e-a 2H
20
Oxygen is the ultimate destination for electrons in respiration
Those electrons are produced by the oxidation of carbon
compounds. The electrons are carried by NADH.
NADH provides 1 H+ (hydride ion) during conversion to NAD+
2 20
2+ 4H:-a 2H
20
The general rule is: Carbons linked to fewer H’s or more O’s are more oxidized.
In general:
Catabolism is oxidative and requires a compensatory reduction of NAD+ to NADH
Anabolism is reductive and requires a compensatory oxidation
of NADPH to NADP+

14. 3 Stages
of
Catabolism
1. Polymers are broken
down into their
building blocks.
2. These building
blocks are broken
down into the acetyl
groups of acetyl-CoA.
3. The end products
are CO
2, water, and
ammonia.

15. 1.Metabolicpathwaysarehighlyconserved.
2.Catabolismtypicallyinvolvesoxidationsand
isenergy-yieldingwhereasanabolismusually
involvesreductionandrequiresenergy.
3.Catabolismand anabolism occur
simultaneouslyinthecellinordertoserve
metabolicneeds.Theprocessesareusually
highlyregulatedandmayoccurinseparate
compartments.

16. 4.Correspondingpathwaysofcatabolismandanabolism
mustdifferinatleastonestepinorderthattheycanbe
independentlyregulated.
5.Manyoftheoxidativereactionsofcatabolisminvolve
thereleaseofreducingequivalents,oftenashydrideions,
whicharetransferredindehydrogenasereactionsfrom
thesubstratestoNAD
+
.
AH
2+NAD
+
A+NADH+H
+
6.Duringanabolismreducingpowerisusuallyprovided
byNADPH.

17. NAD
+
and
NADP
+
participate
exclusively in
two-electron
transfer
reactions.
For example,
alcohols can
be oxidized
to ketonesor
aldehydesvia
hydride
transfer
to NAD(P)
+

18. Only about 10 catabolic intermediates produced by
glycolysis, the citric acid cycle, and the pentose
phosphate pathway are the building blocks for almost all
of anabolism. These are:
Sugar phosphates
triose-phosphate
tetrosephosphate
pentose-phosphate
hexose-phosphate
Ketoacids
pyruvate
oxaloacetate
a-ketoglutarate
Coenzyme A derivatives
acetyl-CoA
succinyl-CoA
Phosphoenolpyruvate

19. ATP and NADPH Couple Anabolism and Catabolism
ATP and NADPH are high energy compounds that are
continuously recycled during metabolism. They are used
for biosynthesis and are regenerated during catabolism.
The average sedentary adult makes over a hundred
kilograms of ATP/day. (They also break down this much)
Note that NADH and FADH
2are only used in catabolism.
ATP has Two Metabolic Roles
A fundamental role of ATP is to drive thermodynamically
unfavorable reactions.
It also serves as an important allostericeffectorin the
regulation of metabolic pathways.

20. AllostericRegulation of Enzyme Activity
The first committed step in a biochemical pathway is
usually allostericallyregulated.
Activators and inhibitors bind at sites distinct from
the active site and alter the conformation of the
enzyme complex.
When glucose levels are high, glucose binds and shifts the
equilibrium to the inactive T state.
When glucose levels are high, glucose binds and shifts the
equilibrium to the inactive T state.

21. Covalent Regulation of Enzyme Activity
e.g. reversible phosphorylation

22. Modulator Proteins
CyclicAMP-dependentproteinkinaseA(PKA)isactivatedwhenthetwo
regulatorysubunitsbindcAMPandthenreleasetheactivecatalytic
subunits.
Anotherexampleisphosphoproteinphosphataseinhibitor-1.Whenitis
phosphorylateditbindstophosphoproteinphosphataseandinhibitsits
activity.

23. Control Sites of Major Metabolic Pathways
A.Glycolysis
B.Gluconeogenesis
C.Citric Acid Cycle
D.Pentose Phosphate Pathway
E.Glycogen Synthesis and Degradation
F.Fatty Acid Synthesis and Degradation

24. Glycogen synthesis
Pentose Phosphate
PathwayFirst committed
step in glycolysis

25. A. Glycolysis
Takes place in the cytosol. Degrades glucose for ATP
production and carbon skeletons for biosynthesis.
Phosphofructokinasecatalyzes 1
st
committed step. It
is the “valve” controlling the rate of glycolysis.
Inhibitors: ATP, citrate
Activators: AMP, F-2,6-BP

26. B.Gluconeogenesis
Occurs mainly in
the liverand
kidneys.
Pruvateis
carboxylatedin
the mitochondria.
The other
reactions occur in
the cytosol.
Glycolysisand
gluconeogenesis
are reciprocally
regulated.

27. If ATP is high
don’t need to
make more ATP
so it inhibits
glycolysis.
If ATP is low then
AMP will be high
and it will activate
glycolysisto
make more ATP.
If ATP is low then
AMP will be high
and it will inhibit
gluconeogenesis,
which uses ATP.

28. C. Citric Acid Cycle
Occurs in the mitochondria.
1 acetyl unit 1 GTP, 3NADH, 1 FADH
2 9 ATP
Respiratory Control:NADH and FADH
2are oxidized
and recycled back to the citric acid cycle only if ADP is
simultaneously phosphorylatedback to ATP.
High ATP inhibits citrate synthaseand isocitrate
dehydrogenase.
High NADH inhibits citrate synthase, isocitrate
dehydrogenase, and a-ketoglutaratedehydrogenase.
-ensures that the rate of the citric acid cycle matches
the need for ATP.

29. Regulation of the
TCA cycle.
The citric acid cycle is regulated
primarily by the concentration of
ATP and NADH. The
keycontrolpoints are the
enzymes:
i) isocitratedehydrogenaseand
ii) α-ketoglutaratedehydrogenase.
Isocitratedehydrogenaseis
allostericallystimulated by ADP,
which enhances the enzyme's
affinity for substrates.

30. D. Pentose Phosphate Pathway
Takes place in the cytosol.
First committed step is catalyzed by glucose-6-phosphate
dehydrogenase.
High NADP+
activates pathway.
Thepentosephosphateshuntisa
semi-independent alternative
pathwaythatparallelsglycolysis.It
generatesthereducingagent
reducednicotinamideadenine
dinucleotidephosphate(NADPH),
whichisindependentoftheNADH
ofoxidativephosphorylation,and
pentoses.Therearetwodistinct
phasesinthepentosephosphate
shunt.Thefirstistheoxidative
phase,inwhichNADPH is
generated,andthesecondisthe
synthesisof5-carbonsugars.

31. E. Glycogen Synthesis and Degradation
Glycogenmetabolismisregulatedbycontrollingthe
activitiesoftwocriticalenzymes,glycogenphosphorylase
andglycogensynthase.
1.Hormonal regulationthroughreversible phosphorylation.
a) Activates phosphorylase.
b) Phosphorylationinactivates glycogen synthase.
2. Allostericregulation
e.g. AMP activates muscle (but not liver) phosphorylase.
High glucose inactivates liver phosphorylase.

32. F. Fatty acid Synthesis
Occurs in cytosol.
Acetyl CoAcarboxylase
catalyzes the 1
st
committed
step.
This step is stimulated by
citrate which increases
when ATP and acetyl CoA
are abundant.

33. G. Fatty acid Degradation
Occurs in the mitochondria where fatty acids are degraded to
acetyl CoAwhich then enter the citric acid cycle if the supply of
oxaloacetateis adequate. Ketonebodies form if oxaloacetate
levels are low.
Carnitinetransports the
fatty acids into the
mitochondria.
Like the citric acid cycle,
b-oxidation can continue
only if NAD
+
and FAD are
regenerated. So, the rate
of fatty acid degradation
is also coupled to the
need for ATP.

34. 4 gal fat
26 gal H
2O

35. Tissues & organs are specialized.

36. •Interactions
between
tissues and
organs are
mediated by
hormone
signals
carried via
bloodstream.

37. •Two distinct
types: white
adipose tissue
and brown
adipose tissue.
•Brown fat has
high levels of
thermogenin,
which are
metabolically
activated by cold
exposure.

38. Key Junctions
Glucose
-6-phosphate
Pyruvate
Acetyl CoA

39. glucose-6-phosphate
pyruvate
acetyl-CoA
glycogen pyruvate ribose-5-P
acetyl-CoA lactate alanine OA
CO
2 fatty acids ketone bodies
Several molecules act as
metabolic junction points

40. Glucose is
phosphorylated after it
enters cells and it cannot
be reconverted to
glucose by most cells.
ATP abundant:
Glycogen
synthesis
favored.
ATP is low: Glycolysisis
favored.
NADPH is low:
Pentose phosphate
pathway favored

42. The major fuel depots in animals are:
-fat stored in adipose tissue
-glycogen in liver and muscle
-protein mainly in skeletal muscle
In general, the order of preference for use of the
different fuels is:
glycogen > fat > protein
Fuel Storage

43. Fuel Use During Exercise
-runningspeeddependsuponrateofATPproduction
-a100msprint(~10sec)ispoweredbystoredATP,
creatinephosphate,andanaerobicglycolysis.
-butina1000mrun(~132sec)creatinephosphatewould
bedepletedandanaerobicglycolysiscannotlastthislong
becauseNAD
+
supplieswouldalsobedepletedandtoo
muchlacticacidwillbeproduced.
-SomeoftherequiredATPwillcomefromoxidative
phosphorylation.–butmuchslower!

44. runningamarathon(~2hrs)wouldcompletelydepletebody
glycogensuppliessoATPisalsomadebyfattyacid
oxidation.Butthisisslow!
Thebestmarathonrunnersconsumeaboutequalamountsof
fattyacidsandglycogenduringarace.
Lowbloodglucoseresultsinanincreaseinglucagonlevels.
Highglucagoncausesfattyacidbreakdowntoacetyl-CoA.
Highacetyl-CoAinhibitspyruvatedehydrogenaseso
pyruvateglucose.
glucose glycogen

45. Contribution of various energy sources
during mild exercise.

46. Brain
-in resting adults, the brain uses 20% of the oxygen
consumed, although it is only ~2% of body mass.
-it has no fuel reserves.
-the brain uses the glucose to make ATP which it
needs to power the Na
+
,K
+
-ATPaseto maintain the
membrane potential necessary for transmission of
nerve impulses.
-glucose is the normal fuel but ketonebodies (e.g.
b-hydroxybutyrate) can partially substitute for
glucose during starvation. The b-hydroxybutyrate
is converted to acetyl-CoAfor energy production
via the citric acid cycle.

47. Muscle
-in resting adults, skeletal muscle uses 30% of the oxygen
consumed, although during intense exercise it may use 90%.
-ATP is needed for muscle contraction and relaxation.
-Resting muscle uses fatty acids, glucose, and ketonebodies
for fuel and makes ATP via oxidative phosphorylation.
-Muscle fatigue (inability to maintain power output) begins
about 20 seconds after maximum exertion and is caused by a
decrease in intramuscular pH as protons are generated during
glycolysis.
-Resting muscle contains about 2% glycogen and an amount of
phosphocreatinecapable of providing enough ATP to power
about 4 seconds of exertion.

48. ORGANS for GLYCOLYSIS & GLUCONEOGENESIS

49. Phosphocreatineserves as a reservoir of
ATP-synthesizing potential.
-during intense muscular activity existing ATP supplies are
exhausted in about 2 seconds. Phosphocreatine
regenerates ATP levels for a few extra seconds.

50. Heart
-functions as a completely aerobic organ.
-the normal fuel is fatty acids which are converted to
acetyl-CoAand oxidized in the citric acid cycle and ATP
is produced by oxidative phosphorylation.
-about half the volume of the cytoplasm of heart muscle
cells made up of mitochondria.
-the heart has low levels of glycogen and little
phosphocreatineso it must always have adequate
oxygen
-in addition to fatty acids the heart also utilizes glucose
and ketonebodies as fuel.

51. Adipose Tissue
-consistsmainlyofcellscalledadipocytesthatdonotreplicate.
-peopleusuallystoreenoughfattosustainenergyproduction
for~3months.
-Adipocyteshaveahighrateofmetabolicactivity-
triacylglycerolmoleculesturnovereveryfewdays.
-normally,freefattyacidsareobtainedfromtheliverforfat
synthesis.
-becauseadipocyteslackglycerolkinasetheycannotrecycle
theglycerolfromfatbreakdownbutmustobtainglycerol-3-
phosphatebyreducingtheDHAPproducedbyglycolysis.
-adipocytesalsoneedglucosetofeedthepentosephosphate
pathwayforNADPHproduction.
-Insulinisrequiredforglucoseuptake.

52. Simple
interelation
between
Glucose
&
Lipid
In LIVER

53. Kidneys
Major function is to produce urine in order to
excrete waste products and maintain osmolarity.
Blood plasma is filtered about 60 times a day.
Most of the material filtered out of the blood is
reabsorbed. This reabsorptionrequires a lot of
energy.
Kidneys are only 0.5% of body mass but consume
10% of the oxygen.
During starvation the kidneys become an important
site of gluconeogenesisand may contribute as
much as half of the blood sugar.

55. Liver
The liver is the metabolic hubof the body. It makes the fuel
that supplies the brain, muscles, and other organs.
The liver plays a central role in the regulation of
carbohydrate, lipid, and amino acidmetabolism.
The liver removes about two-thirdsof the glucoseabsorbed
by the intestine and converts it to glucose-6-phosphate.
glycolysis glycogen ribose-5-phosphate
The liver also makes glucose by gluconeogenesisand
glycogen breakdown and releases it into the blood.

56. The liver also plays a central role in lipid metabolism.
In the well fed statedietary fatty acids are converted to
triacylglycerols(fat) and secreted into the blood as VLDL.
In the fasted statethe liver converts fatty acids into ketone
bodies.
Regulation:
-long chain fatty acids must be esterifiedto carnitinein
order to be transported across inner mitochondrial membrane.
-carnitineacyltransferaseI is inhibited by malonylCoA, the
committed intermediate in fatty acid synthesis.
-when malonylCoAis abundant long chain fatty acids cannot
enter the mitochondrial matrix to be broken down and are
exported to adipose tissue to be stored as fat. But when
malonylCoAis low (fasting state) the fatty acids are broken
down into ketonebodies.

57. Liver-#1
metabolic player
•Primarily
depends on
b-oxidation of fatty
acids for its own
energy needs.

58. The liver also plays a central role in amino acid
metabolism.
The liver removes most of the amino acids
absorbed by the intestine. The priority use is
protein synthesis.
Excess amino acids are deaminatedand converted
into common metabolic intermediates.
-the liver secretes about 30 g of urea/day.
-the a-ketoacidsare used as fuels or for gluconeogenesis.
-a-ketoacidsare the major fuel for the liver itself.

59. TCA Cycle is an excellent example of an amphibolicpathway
Fats, Amino Acids
Carbs, Amino Acids
Amino Acids

60. EVOLUTION CONNECTION: PATHWAYS OF
PHOTOSYNTHESIS AND CELLULAR METABOLISM
Theprocessesofphotosynthesisandcellularmetabolism
consistofseveralverycomplexpathways.Itisgenerally
thoughtthatthefirstcellsaroseinanaqueousenvironment—a
“soup”ofnutrients—probablyonthesurfaceofsomeporous
clays.Ifthesecellsreproducedsuccessfullyandtheirnumbers
climbedsteadily,itfollowsthatthecellswouldbegintodeplete
thenutrientsfromthemediuminwhichtheylivedasthey
shiftedthenutrientsintothecomponentsoftheirownbodies.
Thishypotheticalsituationwouldhaveresultedinnatural
selectionfavoringthoseorganismsthatcouldexistbyusingthe
nutrientsthatremainedintheirenvironmentandby
manipulatingthesenutrientsintomaterialsuponwhichthey
couldsurvive.Selectionwouldfavorthoseorganismsthatcould
extractmaximalvaluefromthenutrientstowhichtheyhad
access.

61. Anearlyformofphotosynthesisdevelopedthatharnessedthesun’senergy
usingwaterasasourceofhydrogenatoms,butthispathwaydidnotproduce
freeoxygen(anoxygenicphotosynthesis).(NOTE:Earlyphotosynthesisdid
notproducefreeoxygenbecauseitdidnotusewaterasthesourceofhydrogenions;
instead,itusedmaterialslikehydrogensulfideandconsequentlyproducedsulfur).It
isthoughtthatglycolysisdevelopedatthistimeandcouldtakeadvantage
ofthesimplesugarsbeingproduced,butthesereactionswereunabletofully
extracttheenergystoredinthecarbohydrates.Thedevelopmentof
glycolysisprobablypredatedtheevolutionofphotosynthesis,asitwaswell
suitedtoextractenergyfrommaterialsspontaneouslyaccumulatinginthe
“primevalsoup.”Alaterformofphotosynthesisusedwaterasasourceof
electronsandhydrogen,andgeneratedfreeoxygen.Overtime,the
atmospherebecameoxygenated,butnotbeforetheoxygenreleased
oxidizedmetalsintheoceanandcreateda“rust”layerinthesediment,
permittingthedatingoftheriseofthefirstoxygenicphotosynthesizers.
Livingthingsadaptedtoexploitthisnewatmospherethatallowedaerobic
respirationasweknowittoevolve.Whenthefullprocessofoxygenic
photosynthesisdevelopedandtheatmospherebecameoxygenated,cells
werefinallyabletousetheoxygenexpelledbyphotosynthesistoextract
considerablymoreenergyfromthesugarmoleculesusingthecitricacid
cycleandoxidativephosphorylation.

62. Summary
Thebreakdownandsynthesisofcarbohydrates,proteins,and
lipidsconnectwiththepathwaysofglucosecatabolism.The
simplesugarsaregalactose,fructose,glycogen,andpentose.
Thesearecatabolizedduringglycolysis.Theaminoacidsfrom
proteinsconnectwithglucosecatabolismthroughpyruvate,
acetylCoA,andcomponentsofthecitricacidcycle.Cholesterol
synthesisstartswithacetylgroups,andthecomponentsof
triglyceridescomefromglycerol-3-phosphatefromglycolysis
andacetylgroupsproducedinthemitochondriafrompyruvate.

63. THANKS
16/04/2019