Diet

+
Glucose
Glycogen
+
Glucose
phosphates 3C02

Pentose phosphate
pathway

Triose
phosphates
..,
A ► ®se-RNA
phosphate ONA

G)
/ Pyruvate _ _,.,. Lactate

>---,. Acylglycerols
(fat)

@fl®
Acetyl-CoA • Fatty
~ acids

Cholesterol

Citric
acid
cycle

2C02

FIGURE 16-2 Overview of carbohydrate metabolism

showing the major pathways and end products. Gluconeogenesis
is not shown.
 153
. f Metabolism & the Provision of Metabolic Fuels
CHAPTER 16 Overview o

Steroids
Triacylglycerol
(fat)

~
~
\I\
..:y
0)01et Fatty acids

~
·," .--
<Z>
~
c:::-
Q)
·-
"'O
~
0
I
Cholesterol

Carbohydrate
Amino acids
l cetyl-CoA ;;;;;;;;;..,._ _@
....J____
Cholesterologenesis
t
J] ~¥t:\'Z..-
Ketone
bodies
OaU-~~fG

Citric ~~'f."\~~~
acid
cycle
l ,~~ul
~~',
~~"'
2C02

FIGURE 16-3 Overview of fatty acid metabolism showing

the major pathways and end products. The ketone bodies are
acetoacetate, 3-hydroxybutyrate, and acetone.
L adequate concentration ot blooa g1ucos~ i~ v u.a.L
Plasma proteins

t
Diet
Carbohydrate
Blood plasma
Glucos
inoaci Protein

Small intestine

FIGURE 16-5 Transport and fate of major carbohydrate and amino acid substrates and metabolites. Note
that there is little free glucose in muscle, since it is rapidly phosphorylated upon entry.
 156 SECTION II Bioenergetics & the Metab 0 II sm ofCarb h
0 ydrates & Lipids

Glycogen Cytosol

il
~ rotein

eentos.e, Endoplasmic
Glucose Reticulum
phosl)hate

JL:J
pathway-

------~Glycerol phosphate Triacylg lyceml Fatty acid~

' 1 4 - =--~·

I Glycolysii - ~... _
Glycerol
-----~ ,,,,"
),,...
'----~~; ,,"
/

Pyruvate

FIGURE 16-7 Intracellular 6i

location and 'o v~J ie* of
majQt:metabolic pathways
in a.liver, parenchymal cell.
(AA_ ~~ 91eJ~.t?o)isrn of one, or
more essential ijmino,,acids;
J T l J' ),d.J 11.J . Jll; i ' ,,.
AA H, metabolism of one or Mitochondrion
I I,-,, . I, • t , d
more nonessent1a ammo ad s.) AA
 164
SECTION II
Bioen
ergetics & the Metaboli
sm of Carbohydrates & Lipids

Acetyl-CoA
Gl'\'o>.v ~• e,,,.._ /;, i,
~ -"f ~~
l- /
(C2)
•CCA\trO\\. (de, \V\ "{ .-:r'-
Ca-r-bo-h-yd_r_at-e~ \ Protein \ [ Lipids]
ifV"lll. -J 1,1
~- :Jl~~~~ I (\.A-Ef)~ -
"-
\iro~~) ~ \V\IG<Co ~ /
Ji~ or- . , -•~ Acetyl-CoA
\ Q~ I ' ( ' ~ ~ (C2)
-~c.o~l
- ff''f Oxaloacetate
Citrate
~ ,.... 2

-1°'~~J (C4) Oxaloacetate (Cs)~ H 2 O

R
(Cs)
Citric acid Ci~aconitate
~~\ cycle (Cs\/' HzO
M \ /
~\/\~
~(A.~ H,O 1C,) 2fi\ 2H~·co,
FIGURE 17-1 The citric acid cycle, illustrating the catalytic Fwnamte (_ .,.Ketoglutarate
role of oxaloacetate.
0.oclnaw
• NAD-.-;;;:t::C,)• CO,
\ . .>U (C4) (C4)

reduced coenzyip.es. The enzymes of the ~itric acid cycle are

located in.the mitochondrial matrix, either free or attached to
. 2H~\}-
the inner ciit ochondrial membrane and-the cdsta mei;nbrane,
where the enzymes and coenzymes of the respiratory chain are
also found (Chapter 13). c!l J b \__ Oxldafive
phosphorylation

Cyt c

REACTIONS Of-THE CITRIC ACID

CYCLE LIBERATE REDUCING
EQU.IVALENTS & CO2 · •,_. ,, ..
Anaerobiosis
• ·· ~ between acetyl-CoA and oxaloacetate to
1

. itial reaction . c (hypoxia, anoxia)

1he ..1n .· . . t--lyzed by citrate synthase, which 1orms a
1

•
.. citrate is ca a f 1 --,,1iri,. i.._,t H .0
forrn
b n-car on
b bond between the methyl carbon o acety -
~(.
car O d he carbonyl carbon of oxaloacetate Figure 17-3 .
)
__,. Respiratory cham- -2

~ Flavoproteih ·
~
--
. •

CoA an ~ bon~he resultant citryl-CoA is hydrolyzed,

thioester . . Cyt Cytochrome
1he . •t ate and C,oASH-an exothermIC reaction.
asing Cl r 1 - ~ ~ - ...
re1e t ~ is ,isomerized to isocitrate by the enzyme FIGURE·17-2 · th'Ercitric·acid cycle: the major catabolic
Citra e . . . .
.
tase
(aconitate h .dratase); the reaction occurs m two
. . pathway for acetyl-CoA-in aerobic organisms. Acetyl-CoA, th
ac0 01s: a ehy;drat~o~,t~ c1~-acomtate an~ rehydration to isoci- product of carbohydrate, protein, and lipid catabolism, is taken
1
ste~ Although c1~rate 1s a symmetric molecule, aconitase into the cycle and oxidized to CO with the release of reducing
trat71 wiih b t~ate -asymmetrically, so that the two car.hon equivalents (2H). Subsequent oxidation of 2H in the respirator)
eacts 1 , i ·t -~~!!"J--- chain leads to phosphorylation of ADP to ATP. For one turn oft
r. 1 th at! are•.J.os m suosequent reaGtions~of. the -cycle are
cycle, nine ATP are generated '-!'ia oxidative phosphorylation ar
atO~~osdtnat ~ ere added from acetyl-CoA. This asymmetric
one ATP (or GTP) arises at substrate level from the conversion '
oot vi~r' is the result of channeling-transfer of the product succinyl-CoA to succinate.
1,eba .L.!.-.thas d' l ,
f citrate-·11 sy l1 • , e irect Y onto fn e active site of aconitase,
0_ah03P entermg free solution . Thie n ~ M •= .L . • '
 E t-J "t'/Mfb_
Th Catabollsm of Acetyl-C~
1I r::.t A. A
CHAPTER17 TheCltrlc~cidCyd~: ,. \ J.-1io( CA A Si f1 v1
l'J
'
'
·1(
~
f' '
v-'
I*
'1' CHa-CO - s-coA
A~ I-CoA
2. c~ r~~
·o , [ Citrate synthase
Malate II
deh~drogenase c-coo- c~ * ::·
1 -
CH 2 -COQ
:3 CH2-coo I
Oxaloacetate Ho Ho-c-coo-
1·c
NAO + H+
• - coo-
HO - CH *
I - GOO-
'CH
NAO+~
~
-,,I
· -, ,
C"'""~
©
~~,c ~ -
1
CH 2 -COO
Citrate
~ --
-

_ _
/ Malate Q wl~ · J~#K, · -: I ,Acooitas8 I
1 .J \ of'>' . Fe2+•· .l _,.
I Fumaras I ~ , HO • * - oc-viu,;if'Oni"'"
"¾i\~
~~ ,lq.\f
. *
H-c-coo-
H20
.
® Q.,.. ~

"f~/@
t'
· 2 ~H 2 - COO

c-coo-
II , 1--
CHrOO
* II
-ooc-·c-H 2 Cis-a~itate
Fumarate q

I Aconitase \• Fe +
2

. .*
. * ,,p) ~~~ ~H 2 -coo-
CH2-coo- ~<, ~~ CH-COO-
~x-~'<.,: ~
i * -
b~~ -_coo;- \
t
'1f!) \;Y f ~s~~;~o~---
No/(Ao:o
I I

·? .
•

CoA-SH ~~v-"""' ~ A- NADH + H+ I j. .

©t
- _ + i ~ r· ~ ~ lsocitrate
•M\ (I),. ._____ • * - . -:;, · dehydrogenase
" ; : ~ J:--- thiokinase . ?H2- CO~~ CH _- coo-
o-, I CH2 I -..r..::..=-- ,,.- \ 2
~~~
\. 'I \,: ✓,
'0-=C· ....... s...:..coA
- + A.A
"11-\ '..p
r_ , CO2 .
_
cl H - co_o-__
.
< -9-,
__,,,
· 'AOf-l.
r
G~ d-.... Succinyl-CoA CH - ·coo- ~ ~ Q= c- coo- ( 1 f/1-0l-!z
, '\ a-Ketoglutarate I 2 ~r--:-: ,ox11osuccinate
f1rO -1- dehydrogenase complex CH 2 • Mn 2+ lsocitrate 1 ,4rp
ti~ L ·~ CoA - SH ___ , I _ - dehydrogenase ,
rn"
Vi~
. ~-"'""
~fll•- ..:. - co O=C-COO
- , .~ / ~
.
/ ~ : ~~~~ . •• _ 2
_ . a-Ketoglut~ate .- , ~~ ..

FIGURE 17-lTh~
citri; acid (Krebs),cycle: Oxidation of~ ADH and FADH~in,the respirato~ ~hain leads to the
formation of ATP via oxidative phosphorylation. ·In order to follow the passage of a&tyl-CoA through the cycle, the
two carbon atoms of the-acetyl radical are shown labeled on the carboxyl carbon (*) and on the methyl carbon (•).
Although two carbon atoms are lost as CO2 in one turn of the cycle, these atoms a~e not'derived from the acetyl-CoA that
has imr1Jediately entered the cycle, but from that pprtion of the citrate molecule that was derived from oxaloacetate.
However, on. completion of a single turn of the cycle, the oxaloacetate that is regenerated is now la9eled, which
leads to labeled GOi•being·evolved during the second turn of the cycle. s·ecause s·ucclnate is a synfmetric compound,
"randomization" of label occurs at this step so that all four carbon atoms of oxaloacetate appear to be laoeled after one
turn of the cycle. During gluconeogenesis, some of the label in oxaloacetate is incorpor~ted into glucose and glycogen
(Figure 20-1 ). The sites of inhibition (0) by fluoroacetate, malonate, and arsenite are indicated.
 CHAPTER 17 The Citric Acid Cycle: The Catabolism of Acetyl-CoA

Hydroxyproline }
Serine
Cysteine
Threonine
Glycine
--------------
\
l·
_!.actate
--

·'
_,i-,/_p-;"«>Jvl'rrf
~40rt i
~ ~ ~·EATP
fi4at7

"J,1-~~'\,:: 1. 5 AW
-1 ~~,.-o~ a,

[ Transaminase I -,~ ..,J DfiHV)(lO~~ 'lt )rW .. 1 /rff'

► Pyruvafe #' •
~---
Tryptophan - - - - - - • Alanine • Acetyl-CoA •
((, f t ' \ ~ ff Pyruvate
.------· .,
Phosphoeno pyruvate carboxylase
carbox kinase
Phosphoenol-
Glucose ◄-----• pyruvate 1( Oxaloacetate .

71' /'
Tyrosine -~:------_..;► fumarate nsaminas
Phenylalanine ~{'

Aspartate I

Citrate

lsoleucine }
~;~~:nine j~~~-~A
- - - - ~ - - -.....

Propionate _ _...f~ ~ ~
->M
=.u.
hl..._____
~111111/~ -
co, j,
1
cx-Ketoglutarate

\ Transaminase
>,

I
Histidine FIGURE 17-4 Involvement of the
Praline
Glutamate
citric acid cycle in transamination and
Glutamine gluconeogenesis. The bold arrows indicat
Arginine-
main pathway of gluconeogenesis.

,. .
 Fatty
acids

-
..
Q)
~::;
,- Py-ruvate
dehydro enase -cii
Q)
0
<tS
Acetyl-CoA 0
cijl
X .
·.a h ,r;"flY, ,

Citric ATP-citrate
acid lyase
cycle
Citrate
Oxaloacetate Citrate - • I

Mitochondrial
membrane ►

FIGURE 17-5 Participation of the citric acid cycle in fatty

acid synthesis from glucose. See also Figure 23-5.