Drvgs r Achons

. 0r
t t st ot
-
rnhi brt s poncreqi L
l l Fse
.
e zefiyli5g
-
reduce chole3tcJol abtorpfrb{) tn s.-1.
ch0pt er l ?
.
ospi ri n. i ndbmet hoci o, phcngl
bui ozonc
i nhi bi t
CDrl + cox2
.
celccoxib
-
innibit coxz
'
ospt r i n
-
r nbr bi t s
T14a
l +
pI o doced bv ect i yof cd
pl oi el ei s
Chopfer
lB
.
srotins
-
tnhiblr HMb CoA red uCtase
-
otorvo
- .t/
Pl0smo
cholesierol
-
f l uvo
-
lovo
-
HOvq
-
t osuvo
-
sl tYl vo
.
choles roming
-
prevent teuploKe of bA
b\ mucosol cclls li1 got
-
gcmfibrozi
| (frDrote)
-
J/-rAa leveK in btood by uP reg. of
p-ox.
Chop rcr
lq
.
neomgcin
-
J
+
tloro
=
.1,
NHe
C hopi er 2l
.
griscoflovin,
hYdontornS,
Phenobarbrtal
- ' l
+uq sgffinase
acrivitv
O
Drsqses
+ enzgme de
f
rLt e
nct bs
ChaPrer
la
O CF
-
mut onon
t o CFTR
gene
-
codes
for
Cl-
chonnel
-
usually
leads
no
wncreatta
tnsuffr'cr'ency
@ TgFe I
-hgper
tiPoproterhem n
-
l i poprorei n l l Pqse
b ry*
ch0prcr
( TA6
-)F
FAs r catgcerol)
-
coenzgmc: dPo ca
Er
-
hg
Perl'lPD ProiBnemra
-
xs chylbmicrons
blc
live/ cdnnot fgsa tnervr up
l b
O zeltNegcr
sgndrome
-
cannot iorge+ proteins fo
Perbxisomes
@
x- rlnrea odrenoleO
Ko d\stroPhY
-
depec+
i n transPDrt
of
@ Ref sum dt seose
Choptr l?
@
eos
-
i nsuf f roenr sorf acranr
product l bn
4/ or
secreri on
-
consf i f oeni . DPPo
(L, S rot i o)
@ Poroxgsmal nocrurnol
hemogl o Dt i ur
r' o
-
dLf i c' encq
i n gl ycosgl
phospnd d\ l i nosl ro\
(6pl )
l . "
Scrves Os cel l sUt
FO(c
pl Dt el i l
@
Ni emonn- Pi ck Di sase
(r9pe n4e)
-
s phing orngel inqse (cannot degtade sphtngoMgclrn
---F-
Ccra
nride
-
lfii' [T""Jt;1i"H*il'o,".o,r .uf or r\sosorne
phosphorsrchorriv)
(-
hg droxglose
0 C Cumul of i or.
0f phgf ani c
oci d
corl rrot go und"er d- o\ i dof t bn (FA)
PerDxi some
membranc
Oftoch ment
si'le
VLCFAs
qcr
oss
t
Refl =1frgtanrc
@
-ray
socrrs
-
bexoomi nrdase A
-
occumul ot i on
of gont i osi des
(6M2)
-
chefrv red mO culo
+
shll-
liKe
incrusrbn
behes
-
cgtopl osm=
f
oam\
0
Fobr\' s Drseose.
'
FAol aL'
'
x-
gotogros ioosc
-
fed dish
-por
plrsh sKt' n fosh
-
x-
linKed
@
Gou
cttcr Dtsc,ose
-
ltsosomo) glucocerc brosidase
-
o ccomu
lotron 0f g lucoccre brostdes
-
mocrophoges
engorged
fll glococcrebrosides
-
c{tDplosm= crumpled fissuc
PqFr
@
kf oDbe Dscase
' A
Oot l l ds Crobsn
-
qol oct 05ql
ceromrdqse
-
glolroid
bodies
i0 N nirc' fno |ter of bnain
@
met4 a6;e110h'c
LeuKod
js
tfophY
-
crtgl sul tdrose A
-
octurvrul otri ,n oF sol Fofi de{
-
demgetrhonbn
@
faruer Dt3
ease
-
ccrofYliliro 054
-
Hoorse crg
-
triisu e
gronulomos
CJloplgl lgt
@ cnotetfthtasrs
@
.rgpe
lt hgpertipioemtu
I
smiih- Lemli- opti"
sgndrome (sLos)
(lar|ostcrot
----
X- Chotesteror)
-
?
-derudro
chol est erol ' a- red ucl oso
L involved in rrigyofion of
dble bond
-
Dilc sdlt defrc r' ercU
-
.1,
BA
in bile
-
def r c-iencg of Mrcfosomal
re(r
filnsFr.pr0tun
-
cannoi toqd apo B
fi ltpfa
@
A bem ttpoprotefnem
ri2
-
def icrtnq of
functlonol
LOL rccqolors
@
tnrotmon dr seo:e
-
connot hgdrolJze l\sosofllol
chole srcrul esterc
@
Tangier d tseose
-
deFl ci nc! oF ABcA\
pr Dt ei n
-
connot l ood cno)esi e16l
gnt o
HDL
@
Conqqnftal Adrenal Hgpsrplasras (ceHs)
(D r-B- Hgdrorgsteroid DH
(pregnenDlone
-{-.
progesfcrore)
-no
srerord
hormones
0t
0ll
Q;
t+- a- l-lgd ro ^9 lase (progester
one
--)F;
l1- a-
Hgd rDi(g prbgesterone)
-
no sex
hormones
or cottisol
'
1 prod.
oi ml nerol ocori i . ol ds
C9 zr- x-
hvdroxgt ose ( l 1-u-
hgo r oxgpro gest er one
-)S
t r oeoxg cort t sor)
(
gogct rcrone *+ ll- Deoxg corFicoslerone)
-
most common
_
cl ossi c:
q[ sspc0
of rrrheral o * gl ucocort i coi ds
-
o\ er
Pf
Dduci i on of ondrqens: / yrdscul i ni zot i on
-F
Vrrl l i zat t on
[ 9 t r-p- Hydroxgt dse
(t l -Deoxgcori sol
-)(>
6911-1t o' ;
( tl- oeox gcorticoster onc
J* cor
tico!ft.ronc
--
dld
osrerone)
-
.,
corflsol
+
oldosteronc
-
l Yl 05
cul rn
i zot i on
l Vi ri l i -zonon
celioc sprue discase
-
mol ol ssor pl -i oh
-
t mmone mc di 0
i ed
@
cys+inurio
domoge t o St
i n response
+o rngest i on
og
sj$sn,
connot opt cl Ke CoAL (cgst i ne
r
ot nrt hi ne,
orgri rri rt
, l y5pnr;
ol l 4 0. q. ' s i n ur r ne
-de
eccl-rvc
tronsPort of trgptophon
@
Hartn,J
p
d rsor aer
@
Pro
--
Pbeng)
o lonr^e bFroxg ldse-
-
or due
l-o BHL+
df icren4
cl oss
i o
hoM0cgsf
i nDrro
-
C rust O1-)lionc
F
sgfiXqse
@
beon enea
cnCin 4- Eeto
ocld Dft
/ - f c t o acr dJ
I n
0f t ne
@ usuo
@
Atbi ni sm
-defect
th +grosrhc merabolbM
:
lAHl
gtaq,
tgro^frwc
-
ARr AD or x- l r i l r eo
@
ntra
ptonurr,a
-
homogcn+is
rc
Ocid oxrdase
-
urrne d4rKens opon stcrBrng
-
blocr pr{mart
in
ear
\
sclcra
@
ecute Intermr*nr
Porphgla ( porpnobih irugen
-)(>
ngro xgtrrfiltbiton
)
-
hgdrorg
thefllglbl)arr
5gn
15q5g
-uri ne
d0rLeni f i erposore
t o
l l ghf
f
oi r
-
n0
phorcsens i tlvitq
congen1/al crg$ropoietrc,
polphyrr'4 ( hgd(oxgmdqlbrlone *> Uroporphgrino?nd)
-
uroPErPhJ rrnogen m synthose
potphgrh cu+onea- furaa
(iroprpngrinogcn a
*+
coproporPhgrinoqen d)
-
uroFr
phgrinugen
decArborglose
Hered I
rary
c6ptopo,
pngr,
(copro"pot
prgrrnqen
f, tts
protoprpryrrnogen
e)
-
coproporPhgrrnogqn 6xf64se
@
erg*rroporctrb
protoporpngria (
protoPorpngrln Il
-+
henle)
-
Ferroche lorase
@
utgler-
l.loJ jar r +a (
bitrrubt'n
--='
sltrlobin
diglucuronidc)
'
bi l i f 0bt h
9l
uc u r ong) t r0nsFerose.
@
ouuin-.yortnson sgndrome
-delectrvc
tromport
pro'"in
(fiom
tiver6
bile canicotD
@
Enzgme
s
*
CDe
nzgms
l coFdctors
chqptcr l b
o ocerul
c-oA carbo).gl4se
-
coBn-agrnc
I
bl otr
n
@ otrorc
,
insu
tin (
d epnosphDrglofiDn)
o LCFA
, gl ocagonl epi ne
phri nc ( phosphorgl ot
on)
@ cornrt i nc pnl rrrf Dgl - rronsf i erose r (cpr-r)
o rqol ongl -coA
G) proprongl coA c6rburglose
Iproprongl
CoA
------------+
D
-rneiiqtntato^g
t coA)
" crce ragmc
r
biotln
6l
nrc*ryt nt Ol ongl coA rl rut ase (L-
mct ngt mOl ongl con
-X-5
sucCrngl co*)
'
CDenz9me
yrf.
B12
'
t f nol WorKi ng
:
Occomul ot t bn
Cf r
Hopl onot e
+
ms. rhgl Mol onoi -e
chqpt er
l a
l o Dr l ne
o Ps de corb0xg
lose
.
cofoctorr
pglidoxdl
PhosPhole
(vr+.6.;
@,
Phospi l ol i pase Az
' oct s
on PI
t o f eCo: e orochr donrc oci d
O glu co corti Co r' ds ( i. e
.
cor
tisol)
@
t rl psrn, bl l e sol t s
Chnpfer lB
@
hMh
coA re ductose
( Hutr c.oR
-----------'
Mcvalonic
Acld)
.ER
mem brone enzgMe
O chorest crot
,
AMPK ( pnosPnorgl dks), gl vcogon
,
st ot i ns
@
phosphot ose
(dePhos
Phorgl ol cs)'
rnsgl rn
O
@
chol esterol
-1' 0.-
Hgd.roxj l ose
(chol esi crol
--=
c,691i c
Ocrd)
O cho \ i c Oi l d
@ ch otesferol
choptcr lq
)
o mrnotronsFeroscs
.
COfocl-or, p\ridDxol phosPhoto
(vrt.Ba)
(9
coruomogl
-
Pbospnore 6gnrne
ms a
(Co.' NHs
.--.-->
Carmtnogt
@)
@ t t - ocergt gt ot omore
Chopter zo
,7y asparqginse
(osporogine
--=
osturmte)
-
c hemo
er4Ery
lreat Menr
@,
Hrst i 6ose
( ht sddr; t a
+
urgni c
ocrd)
-
CoFacrcr' pt ri dDrol pno! PhdFc
(vrt , ar)
@.
rretu
7;--
gluiorYn
,l
THF
J
5-
formrntino
-
THF
-
Forrc ooi d
qef f ci enq,
Cl o
Fl qt u
exCrenon f cs1- (f Ft rrt u
=
cl ef t crarrl j )
' Qj
serlne nijd r \, r9me gl rr0nsl.r&se
(
ot1
----+
s..;
.
1s, N
lo
-
r,nct glenc THF
---s'
THF
@
aur
(i,
sam
.coPoctor
is
FJrrdoxar
pthsprrt'
(vrt, e")
@
PrEng)ol oni o(
hl , d rL^Jl ose
.
coenzgme: Bft+
--->
*n,
.
cofqctDh,
rYre n'ryl co b
a lo mtn
(9
crgsran
i)"nc
-B'sV^UlQte
+
sgnlnos
e
' coPOct or:
M92+
ryf e
I i onrt e 6gnrnase
@
( vrt. 412)
f;rg5la
fltiunose
''sofoc+or' p'vrt
joxar
PnosPho1"
(vrt- Be)
@
vol i oc, rsol uci ne
-= ->
propi ongl -coA
'
biotfn ,
vrt. BtZ
@ orcncnd cmin A- Keto crcid DH
'
c+4ctor3i
TPP
(vr+ 8,)
tipoic octd,CoA (vrr. tss)
FAD'
NAD
J
^
Vvrt
6s
Vt+
Bz
@
ptoprbngt
CDA
+
methgllvMlohgl co^
,
' bl ohn
O
tncfhgl
molongl CoA
-----+
luccrngl
-coA
.
copolaDin
(
vrt.
Brz)
@
@
ALA sgn+nose ( bt g. spcci ngt coA >
ALA)
.
coenqmet plfidoxat pnosph4F
(Vrt
05;
Q
hemin
@
serine hgdroxg i\1c ty}gl t(tnslrose (
seirne
71
gtVcrnc)
,tl
tlrF
J
Nt,Nto
-
Mc+.+ryIene THF
@
nrn
oengC rarase (ALA
--;
porphobilrnqco)
O Lcqd
9
Ferro chetotose
O Lrod
. . .
K-2 T'J ro
s
rh e Hy dr oxy I
c(S c
.
coFac+or:
Co
Fq$l
Acid I Tnqcgtgtycerot MemboltiM
-
chqp+c( 16
@ strucrure of FAs
'
f erMt nol
carboryl groop
,
pKd= +. 8
@
sotu
rotion of Fes
.
no double
bonds
=
soturo+ed
'
)l
double
bord=
unsoturoted
-
cis pos rtrbn
-
i F
z
or f f ore doubt e bonds, ot way:
spoccd
ql . 3C
t ht ervol s
bend or "Krnts"
-
oddition of doubte
bonds
=
.1, Tirn
o
@
cnoin lengfis of
FAs
od
v,
Ho
''f
;T
.-'r.t..,^'.-^1r'iHs
tb
co
0<
' orqcni dOni C
Aci dt
. cn- L
FA
-
doubl e
bond
i r ol - C6
Q
essentrbr
rns
.
ont l z
ore esseni ul
O
L inoleic acid
=r
prccursor
of arcbr
donrb octb + prostog/qndrhs
@itrnolenic ocid
+ prc
cursor oF d-3 FAs
(growfh+
oteve lopmer*)
'
essent i ol FA
det t CErEy= scot y
dernnri t s, vt suat r
neurol ogi c
Obnoryhol i t l es
@
q"
49uo
r-
A sgnrhcsis
O Productton of
cglosrotrc ocergl
-coA
'
+rqnsfer
ccetote units
fuom mrbcnmdrbt
-
,vtitDohord rtilJ ace+gt
CaA prod0ced
Ocetgt
-
6pa to rh
gfosol
bry:
l.
oridotfon
oF
p\f
o\ote
z. cotabol r' sm oF FAs, ketone bodi es, ccrfoi n
o.a.s
'
Note:
coA
cannot cross /hembrarE
t)
..
noN
do
uc
9er
i t Inro cvtosol then?
Cohveff to CrrRATe,
oAA
.r
ACcryl - coA
l
. , rro"
sqndnse
h'
$
to^
M ATFU
cYT0SO L
AOP+pi
\ l l r /
OAA
r;
ceig- cDAl:
, / l l
I t \ \
@
car nor gt ot t bn
of
qcet gl - coA
to
Porm
ryl ol Ongl ' Con
Ac
etgl-Co
A
cttrote
occ\ l
-
c4^
corDC {q l ose
(
to^
h1P- drrAte
l qate
coz
Qcc 19) CcA cor boxq l qsa
'
roqunes Hcot +
ATP
.coenzgme
i
vrt. blotD (bouna to llsyl
fesiaa)
'
eote
-
trhr hg 4 fegotototg steP
'
@ alrare
.
O LCFA
.
shori
terfi
feg o lorion
-
rhoc tivorion bt
PhosilDry
lonon
.
ePr ne
Pht -
l nc or
gl uLqgon, AMPk
-
oci rvot-i on bt
de
Phosphorg
\onon
'
i hsu t i n
j.,)
motonyl-
CDA
@
9FoHt
qci d 69n+hqse: mul tl
functronal
enzgfl l c rn
cdKqrgorcs
-
drmcri c Orotei "
ft 1
drei corqt\nt domOi ns
'
o Cgsl
ei nc rei l duc
, \^rhi ch octs os o
' por
ki ng stt""
for
i n+ermedarc.
' A9t
Cortt.r Prorci n
(AcP)
si rc
-
coenzgfnc:
.l ' -
phospho
Pontetbei ne
stcps in th Sgn thc56 of pol mttote
. . .
(6t' "
+
ocergr-coA
,
["9' *;
5!*0," ol
o"9'
coA- AcP
, l
oceryl
f runsocgl ase
i l '
coa
/f,
O omol edJl e of oce+q t s i r ansger r ca
from
occ+gt coA l D the
-sH
grouPoF
ACP
@].*,n
I | )
@ Nert,
ocerqre
1zc' s)
rs frqn st errcd
to
L
AcP+s-ocetoft
o temporqrj hOl ai ng si te
-
rhe rhrbl
I
grouP of
a cisfirne feeidt'c o^
rhe enqttc
@l
J
fTiD' -o"' *o"
L
^cl;|sH
+
r \ ' ' l ol ongl - CoA
@ no*- uo. on* ACp occept s
o r uat onor e
( 3c)
|
oni t l l ofi
mal ongl coA
@
|
r'toto ngr c'oA
-
AcP
I t r onsaSl ase
.,t/
(-li+
s- oce+o
L:"-;f-t-
moronote
@
mor ongr
t Dse Hcoj
or i gi nat r ;
qdded
b. ,
qcetyf coA
C.arb}\gl asc
-
thi s
focrl rmres
i +s nocEop,ni tr' c
ottocR on th ocs
re.r Pqnd
l i rrhg
qcet gt
gr oDp
b g= r esr du"
-
f esul J: *C
Uni t OuQc/ ) ed
t o
AcP
@ ret group is
redr;cedfD On Ol conol
l . - Acp
rc
at
o(
' 5
r ic'
lcg
5e
r ot
ona
toc
ha:
cei (
ol o
Ken
rn th
oc
m(
- k
s9r
5-
.4
r
rs
@
J
coz
oF h2o
is remo/ed
doobt e Dond
o Motc cul c
llttoduce cl
@
rro"o*
1l
@)l r-r. nu. Vt -nce
n^oo*
y' J.-**
r;D-" ? 3*
\39!J-
s
-i -
cHa-
c- cH3
I'
@13
-
t l gdt o\ gac9l
-
^cP
/ l
dengd romse
*uI
@)s' o
Lcgf
t- 3-.":."-.nt
n^oou
--l
@)l
enoYt' AcP I ed, crase
"^oor
y'J
[t]' " e ?
( r cPj - s-
d- cH2- c- cH"
*o
S
-
c- ct t r-
cu; cx,
(D
rhc
dooble bond is rc d oced
{.' ' Tt
[9
@
r P
31
c0r
l s
r va
@
rm
0r
tc
|nal c\ afc
folly
sqrorqred
otirq
o zc
un''r dcrivcd
Prom
rmrrnOl ed f. ACP-
S
-Pal ml fogl
cys lD lrc
r'rA
DP
H
tc
rc
@ De
sa+oro+tbn
of FA chqtns
'
e nzglrcs
fo ER
do tnis
'
mi I ed
Funci ' r6n
oxrdoses
" rcquti c
AIADH
+ oz
@
Sl orcac
of FAs
qs
TAGS
.
FAs
orc estcriprta
tnroqh +hcir
carborql
g(ooPs
-
res\rtls in loss of,
-ve
cndrgc 4
ftrmotrbn
of
' t
ncvfrdt'
fat'
.
sfr0 Crurc o
F
7A(x
l l
cH2- O- L- sot ur dt cd
Fn
l o
, t l
Lnz-
o
- ' c
-
unsot ur ol - ed
FA
I
rQ
Cl .z- O
-
i
-
el ther
'
storagc
oF
-IAcrs
TAEt
coci l cscc
u\| tnl r odrp ocrj fc<
tc
fDrnr
oi l g
droptets +har are t)eat t\ anl )gc]r(,c,
'
sgnt he si s ( r i
9l \ Cer cj i
pr l ospt l di e
-
Z
Pcrl
nh./ays
o
l r ver + odt pose t i sj uc
@ l i ver ont r ;
c?l gcerol
Gl gccr ol - G)
N0r cj
odi Pocgr cr
can ant t 0pt qFc gl ucose,
, n
r he pr eseocc
of
' con\ r cr sl bn
of on FFA t r : i r s 66t 1y6166 pu nl
F4hy ocl j )
- coA
'
t ' r or , . ,
r hot we hove DLt t t sr bsl t a| es
nceded
i u nt ct Kc a f l , | ' ,
wc cqn
1a
on. ad
ond synr hesr i e
i l
. .
o
l u co l ' l s l s
I
J,
J
DHAP
I
I
l '
J
Gl gcerot
sgnrnesis Df
q
nlole c.ote ol TAq
(rlgcerol

Fo$t
ocl FcoA
Acgt-t ron sterase
CoA
L\sophosptnfidr'c ocid
Fo HY
, ocgl -coA
AcgltronsPerose
CoA
Phosphotrdl b oci d
(pA)
' oKa.
DAq- O
Pno!phomsc
?i
A9l l TOnSFcr ct s"
CoA
TAq
@
rotes of
.rnq
' l n
odr - pol e
+l s sue
-
'TAA
s tDred
rn qtosot
, in 0e ty
-
"
fot dcpor'
,
l ^ l t vcr
-
l rttl e 15 s i ,Drcd
-
packaged
W O Choksl crgl esrers
Nott' Ch,toMr
cron! deti ver
dr.taty (erogno(,i19
den;cd
)
ti pi ds
@
H20
Ahgdtot$,
tolm
V LDL
@ cYutcstcrot
O
PhospholiPids
O opDl i Protei n b-roo
DAq
-
vLDr.s
cl cl rvcr endogcnousty denved l i prbs t6 pcrr phcral +l ssuas
@
Mobi l i zotl bn of
s i ored
fqrs
4
(E Rel eose oF FAs
FrorYl
TA(?
@
v
/
h,6pnomss
fqte
of gl l crrol
-
connot Dc metobol tzcd
bg
Odl pocl tes Dl o tIFg
l OcK cl l gCerol Kl hase
-
." i rqnsportcd +hroDgr) bl ood
to l tver
FFAS moy l hrougtr cetl mcdbrant. ol acJ(toc4ra
l bna abtUnrh
frons ported to tri soes
--t
enter cel l s
4 octi voted
to coA denvdfl ves
=)
ox;dr;ed
For
encry
FFA5
cannor
be ui ed bV:
o
RBCS
-
| acK mttl )choMfh
(3
bratn
-
cannor
cross BBB
o
a
t
oxl dar ton of FAS
C AMP
O
epl ncphnne
l gl ucagon bti tds l o rcccpbr
on cc narhbfonc
@ Occuprba
rccePlor rntetocts
fi
(:a
prorain
@
Os
Protctn
ocl l vds od cngl 9l c,gcl ase
@ Odengl gl oj l ose convertr
A-rP l Dto CAMP
t Nhi ch Sef ves As I nt f qCcl l ul or sr qnaI
@
CAMP ocnvoEs PK
@ oc+i v. PK phosphrgl ates notfi i Lrrc
sensr i i ' e
Lr pq5e
( H5L)
|
f hcr cay act i r qr vq
l f
@
HSL rcmoves
FA
From
c1 dndl or C3Df 7A(1
Noi t : l =A
sgnt hesi s rs t onned of f v{nen
TAcl d.cg
roddtl
on rs t0trEd on
,
in t|j. presence of
' l
insolin or
glgcore
plo5vmo levels
Hs t is
de pnosPhorglota
(rhocrivotco)
t
HSL
( , n0" ' i ' d\
, l r p
, '
\fo
@octi i c
PK
l
g
/>t,.e
HsL
k/
(
ac ri vc)
\r,
I
)
i
TAq
I
I
l\m'
.l -
DA
(1
f oi
ot FAs
|e)
@
p- ondal'lo" oP res
' 2C
oni r t Qr e socct st vet y
r er oved
Fr om
Car boxgt f et t ui t bt Of f O* y
Acgt COA,
Producrng Ocei yl
CDF
11' !ADH I
FADH2
'
t r qnspor f LcFA i nr c r t 4l l ochondr i on
-
LCFA en te, s cell
-
con verted fi:)
+
enzgme rs por.r- of ootcr
mrlochbndrnl ncrflbto,ne-
-
how do you ger
l-al\
acgl cln
inh mr Jochondrrbn
?
carn;tirc
6 h,tfle
LCFA
rh roK | 03sg
X' car n' +i , *
Pot ^t t
r u\ !
"
+t qnsf et at e r GP
t ' L)
-
OKA CAT I
'
.Emal ongl cDA
t -
caT l t o( aAr -
I f
Cor hr f i ne
FoHY a c9l coA
Fo+|.,
qcgt
Co
)
r'
cornrltirc
CoA
Fa HY oc.Vl
-
@rnrtthe
cYlDs0l t Ms maltt
x
N oter FA ottdte+to.
atsa regdal A!
by
ACcryl CoA:
CDA f ati 5
; 45
16t r 9 |
,
t hi Ol ase aLhv; r g v
soulces oF Corn:t+inc ?
O drbt
@ f rot n
o. a. Lys
+ Mel
--
only ,h lrver
I
ts idncy
cdr nl t l t \ c del t ci cnaes
' I'
obi ttl !
of
fl ssues
.ro
osc LCFA
os a mctubol tc
fucl
'
occur t l h:
D Pi s
fr
l rver di seorc (no
Carni nhc
sg.FrEsti )
z) MolnDtritu6n or sftEl-
Vcgeflrian
dtert
)
1 cat ni tine
fegoiremcn)
( prcAnanr womeh, t n
Fecl
t 6n
I
bu r ns,+rQstna)
_
4) peoPE
undcrgorrg hcnrodialysri
-
cPT-T
de
fr.cri rrcg
occors
pri rnari l y ,4 l ri er
-a
conho+ osc LaFA
fD(
e(trgy l o sgnrnesr' zc
,l ocose
dorthg o
Fas+
'
cP' t ' \
deFt dency
Occor s pr t monl y i n car dt ac
+
sr cl et ut mAscl e
--.
catdi ontgopfl .v
f o+\ acAl - coA
D\ LcFocgt cLA sqt l r h' r ase
( i n' c' r t " " I e)
/cqf,nt+inc
(
\
ro* o.r,-
CDA
SCFA + MctA ( <
l 2c)
cross i nnr
p
-orfaq11.,
Fa+lY Acyl
-
CoA
Hzo
enugl
CaA t-fsd rOi4se
3- Hydroxgqc.gl coA
NAO+ 3- t +\ dt
qgo( 41
OOA
DH
NAo H
3
-rctoocat
c0A
coA
B
-
kc
ta
Acgl CoA
1.ni al asa
FoHy
ocAl CoA
+
Acet t
coA
-
E nerg! yteld
:
mrto. ntcmDrane
t^rft)
c1rnlnc Sr],ofile
cnr- Gn)' -
cHz'
cqz
'
a2
I
B-
cdrbon
c-
I
S- CDA
too
\ l o*,
"o^
@J
I
aengarog errascs
FADt t z(
|
LcFAt McFa' . . t o
O
I
\y
enoyl coA
pnl mt+oyl
coh
-+
COz
+ HzO
.
I oce+gl
-
co n
.
? NADI I
.
a
F^DU
=
l3l A'rP
-
' -
t24 A' tP I
MCF acgt CoA DH def i cr ency
. Ae
' ,
FA
oxi dof ' ron
'
Severc hgpogtyccm14
'
rfeot
fiitnt
-
corb- n'cfr dtat
. ' oFf cct s
nTant s b1c mi t z
conlotnt MCFA
2 A' l P (acl ;vo+' on of p.tmt+arc)
{
Rot c oF 5- HT ( scr o+oni n)
-
Porh PercepJ-l on
'
rc go l of
rbn
o
t
' sl ecP
' f cmp
, BP
TryPtoPhon
1."
--\l'
)
lHYdro''erose
J
5- ltydroxy
-
Tr gptoPhan
I
; l
Dc carDoxY
l ase
co2y' f,
Htd roxg frgP to rnrrr (5
8HP
DHP
+ HZO
5-
Clc0tt'ne
'
found
in m96ctc
' 69^i hesi s
Argi ni nc
ornrihinc
HT)
Hzo
v)
Amidina
rrons
ferase
CtoonidinD occtqte
A'l?
Pre,scocc
oi Creartne
<t nasc
i n
pl osma
=
MT
Cre
ATP
\
I
I
^nP)
ctearin
0^r-\l
s^H
)
l Mcthgr
ffdnsrcrose
otlne
CreOl tnc
6r hose
ADP
phosphata
c rea t i ni ne
'
degrodari on
of
creot i ne
-
Cl eAt i nr n , s ex cr e t d
-
muscl e
moss
can be ssf. bV Ue1ti mi c excrc l ed
-i
When mu(
cl e rndtJ .1,
/
Cteot tnt:ne i r, 0r
nt {
-
Kl dneg
f ar l ur e
i
r
r cot i n i ne ( pt asnn) 4
-
nor nl ol
o? :
t 5 mr nol
l day
Cr ear i ni nc C\ Cr et ed
@
Mc l o nr n
'
59nt
ne sr zed
l r om
t Yr osi ne
.
r n mr I
qnD
ar r t s u{ epr deymi s
'
def eC+
' ^
me l oni n pr uduct t On
=
ul Dl r l *nt
b
duc
t o de f e
c+i ve r nzgme=
@
ori dofrbn of
edd
r+
CrS
-
6amc Os
fo(
even
t+
on+tl
ftn' .l
3 C' s al e teQchcd
@
propron;t
con
.
coenlgmc
carboxgl ase
r s brbt,h
Pr opr onyl
- coA
^";16,ffi,'
."^
ADP
e/Icatbo\gtose
D
-
me+hgl nl al mgl coA
ROCC mOSe
metl yl mal ongl ca h mutase
' coenzgme
vi . 82
.
Vf t
8, 2 aef i cGn<4
'
propionate
+
methgl
rflalonart
in
otinc
oxi dot i on o+ unsoi orored
FAs
-
providcs
,b energy tt:pn sat)r,fed
-
ora,
ol /nohD
unso furate
d FAs req.oties
:
3, 2
-
. nog! coa t i omerqs c
-"
converi s 3
-t
rohs fo 2
-trqns
.' ,
c4n Scrvz aS ,ubstrate
l or
enogt
C0A hgdratasc
-
o*.
of pot\ onsal ora+ed FAs
(equrcs:
atz-
enaqt coA tsomcrate
+
NADPH
-
de pcndcnt 2,4-d6nogt Aa
rcavcw"
@
@
p
-
oxi dat i on
-
VL cFAs
-
i rir tia
I
rn
PCrOt
i ,sorncs
[
)zo ct) ordergo ge
lipinary B-
ox, iA
WrDxisomes
dehgdrogenqf i on rxn:
Fao-coot ai ni ng acgl coA ort l &sc
Produces
FADH2
FADtf2
X
o2
uror-9!9J3-1 a.o
'
de| ec+ n +ar gel i ng
Pr ot et nr
fo
Peruxl
soffles
=leltwcger
Syodrcne
'
deFeci
tf4Dspor+ of vLcFA 4cros<
perD(i soD membl arE
=
,(- l t;Ked
adreno lcut.o d\6t1.oD'1l
I'A D
.
x- or i doftbn ol FA<
-
br anr ncd chai t FA: phy+Ani C
ocl d
->
cannot ondergo p-ox.
DIC i + c}n+ ai ns CH3 gtot-l o on Cs
(6-c)
:
hydr or yl or cd
e
d- c b\
FA
4- n: / dr - r l l ose
+
Pt odoct
i s decar bor gl Od ond CDnver r ed
+o
CoA
t or M
+
can
90
Undcr p, ox.
^
QePsom c)t seosel
. Ae
'
de
f
r cr ent
enzgmci
^
- h| dr t l gl osL
' q
ccumu, ar i on oF
ph\ +ani c
oci d i n
Pl osmo
*
t t ssues
.
ncurDl Dgrb 6 ymptoms
'
tl gotrrcnf, d\etor\ tec +ri crtbn
@
Ker on" Bodr es'
ol f cr nor c
Fuel f or
cel l s
,
QceloQcc+ate
t
3- nydroxy bvtgratt '
oce tono
'
acer Docet ot e +
J- hgdt oxgb0t gl l r c or t t t ani pol t ed i n bl ood t o
Pet i PhcYol
+i ssuct
-+
re convef ftd +D ocetat Cat\
-
l mpor t dnf
6o0r ccs oF encr Y
For Per i Phcr ol
i r bsucr bl c:
D
sol r r bt e
I n oqUcoos sol r n
")
pr Dduced i n i l ver , r { hen ocef gt CoR r s i n xS
s)
U5ed
i n proporti on fo tnej r concentroti on rh bl ood bV cordl oc
nl o scl e
+
tenal cotl -cx.
@
sgnt hesi s oF rcrone bodres t r7 l l ve Lcrogencsrs
Fony
qsgl
66a 2
/ A. c\ t
CoA
\ , /
r / " ' t
" " '
\ / (
\ / 9coa
{ 12
A CeiD
qc,c+gl
CoA
| /.-
occ+9t coA
l'
I
t 4t t )d i _AA
l >t 1L): t t ct sa
\ - ^
-HMl
COA
la/
HME
CoA
I
HMq @A
It
J\
occter
A CctoOcC+Otg
l \ ose
CoA
NAD}I
3- HVd rolg b' ururoie
DH
egui tiurium blw o cebqcetatc
+
3- hgdro{9butg
rota rs
determined D) NAD+
/NAon
rolio
"r"rron*f
"""1/
NnD+
A cci onc
3
-Hgd
roxg botgrorc
'
Norr; fi vcr rs vnabrc fousc Ee ron bodrtt as Foel
bl c i l
l acKs
++i ophorose
rorc oF rerone bodrcs producfrbn
; rqte
of u3e
=
Kctonemi a
- Kei ohc
bodl ts i n urr' nc- astanotl ,
+l l ,ese 2 condi hbns seen i n uncont fol l ed Typc I D,abetc. mcuttus
-
hqn FA degFodar;on
=
xs acetgt
coA
-
depfeti on of NAD+ p@t t
+ NAoH ,rol
=
sl ows TcA cycl c
-
di oDei l c tcc to oci dosi s
=
ffutf^9
od
our
On
brofh
-='
d ue l o
'l'|
ace.torre prodo
ction
'
car boxgl groop ol kct one has pKa"+
"'
l oscs Hr
-
J
PH
of DodY
'
excrcri on
al Ket nne bodri s i n urt nc
=
de hgdrat i on
-' ,
.I
Dlasnn Vol umc
=
xvere Acidosi,
Cont pl c! Li pi d
MCt qbot f s^a
-
CHApf eR l ?
@
si rucfi rre op prrospnotrpi as
-
2
closses
A +'rosc +hor td't.
gl\caol
os bactbonc
@
thote +t:nr conrain sphingosine
@ Elyccrophospholipids
' Contotn
9!\
cCrol
'
dtl conroi ^ pnopnoti orL
cci a
(fi
t
phos
Pnorcglo{F on 3'a 6arocrr)
a
o
l l
o
_
c-^,\,\,^/\.^\,^,^l/
o- c-v\
/\,\/V\,,\^/\,/
bPa
'
grgcerophosplrolrpid
=
en
+ qtcortol
-
Ogroup can be esrclrfiid to onorhercmpd:
phosprta+idtl serrne (p5)
Ph
Osphal ld.glQfllanolamtnc
(
PE)
phosphoti dyl chDl i n.
(Pc)
phosphofi dyl ;nosi +ol (pr)
phosphoridgl gtgcerot
(
p6)
seY I nc
ethonOl ofti nc
choline
l no s$ol
Gl u cctDl
cdr di ol i pr h
=
2\ pA + ggcdol
-
foond
i ^ boci a { eukoryos
-
exclusrye tD r4ner mrJDCJDndriat ftcfqbrAr|c
-
l \l ohtenancc Of
Certai n nesprrqtory Compl el cs
-
onh
genic (.e
Cognizea br,| Onnboaier)
Plo,imalage|ls
-
FA
@
C1 i s rcp|aced by Uhsotutored
otKvt gfoop +
ti oi 1 aehed vta
a^ ctl rer
(@+ltcr lian an este-r)
lfirqq.
-
exarnpl e s
i
pDosptrt +r dal c thanolaminc
,
obd+.
in rerve +rssue
Phospmi
dol chol i nc
j
qbdt
i ^ heart muscte
Ploielet
-
Aciivonig Fqc.ror (pA")
-
unus val
-
-
FA
)
ct i s e+ner ti n*ed
t FA
e
Cz
i ( rpteced
bJ acctgl resrdue
-
bl hds
to sorfqcc receptors =
potent thronl mnc
+ OcutL
Inpl qmMarorg erenrs
-
tnvot!sd
rn' hgpersensi ti vrtt
,
ocute Infl qmmartor), anapnl l qi c
ns
-
Causcs pl qtcl et5 i o qggreEorc
l degrAnDl aE {
qtvcol 4r
i %ros +o m4r supercr(t;e
rods.
@
spnrngo pnosphol i pi dr: sphi ngorhgel i n
'
bogr uone
=
of i r ho
ot cohol sphi ngosi ne
-
LSFA ah ocytcd
+o
ami no grouf)
-
ql cohol
gl ot j p
@Cl
i < egt er i f l ed
.
tftportdnt constr
tuni i n mgel ri r
of
+n(aqh ami de l thxoge
=
Ccfami dc
to phosphorgl chol ,n c
ncrve
fiDers
@ Pbosphol i pi d
sgnl aE si s
'
orc of 2 \^ra) s:
O
CDP' DAG r Ol cono
I
@
coP- ol conol
+
r ) 2- DAcl
'
cop-
boond
stru ci ure
=
oci tYoftd
l tfcrmedi atc
-
CMP rel c
q(e
d as o si d pdr.
.
occurs
i n
SER
b
Gotgr
-+
0Lmbrones
of orgqnel l es
o.
pM
or sccreted by exo' c9-tosi s
,
NOI-e:
ql r
ccl l s can Sqn+hcsri c
Phosqrol i pi ds
(cxcepr mo+ore FeCs)
@
sqn+nesr. of PA
Qlgceror @
fo\
oatt-CoA
I
-
\ l Ac{ . r .
' ' 0' , - . .
t r , l
\l
"Nt"oo
L\so
pnosphondi c o ci d
I
p\ogt'c.on
I
\ l o*,
: J, . , ' . r - { \ t
u$
*^
ee (prr: -@)
@ sgntncsi s of
p
1PC
'
Pc
I
p =
rnosr obdt
' Uscs
et n onol OMr nc
or
. i n
l l ver PC
can ct l so
chotrne
from:
O
dlcr
@
turnover
be s9n fle srzed
ff
om
ol
body phospnol i prds
PSl Pe
'
sgni nesi s qf Pe+Pc
i r oM Pr c
exr st i ng ei honol
aMi ne +chol r ne
O phosphorgl ol i on of chol l he or
cthanol ami nc
by nrnas:s
O
conversi on to cDP-chol i 4'
or cDP- c:.h.anol afi tn'
I
ttons
Fer
ot' c
aP bound nole cole
io DAq
'
hurnons c4n sgn
+hesi zc chol i ne
d9 D!4!-9
,
bot
omounl tnacl e
-
chol fhe Ol so used i n sq^tne.G of
q' e+gt
chol tne
i :
t ns ot P i ci en+
-
DPPc (di pql mi rogl phosphatl ' d!l chol i nc)
'
c1 { C2 d. c Qt t ached t o
Pal mi mr c
' mcdc
+ sccr et ed bY Tgpe 4
Pr Eumocr j f es
'
M4j or l rpi d coryrp orEnt
of
sorf4cFent
'
! sur gacc @
'
RDS: Rcr PUal Or g
DNi f ess Sj ndr or ne
-
i nsttTTi Zent'
surfactont
Pfoducti on
+f
or sccte|.on
-
l uog rvroruri rg i ^
ftos
6i rff
i d
by:
>2
= ' ndtute
L (
Dppc' )
r
s
l sphi n4cn
get i n. )
( dnay'
<2
j
t mr nai ) r o
-
l ung mdturi tY can be
qcccl croted
b, grvtrr?
/}|D ffEr
gl ucocor+rcoi ds
shDI tl , l 2CFore del rYerg
sgrhhcsi r oF Pc l rorb Ps ( i n l Ner
):
-
l l vet cxPor l s Pc i r l
bi l c saHs + q5 componcnr oF Ser uf 4 t i popr ot ei nt
al ecoi DU, ^! r
l Asr t
r' c4urtr pyri dox4l phosPhd i c
I
I
I
I
Pt
t\
t\
Y
T
\.vz
J
PC
@
sgfttnesi r
oF Ps
-
el h
qnol amt n
-
revYsi bl e
I
3x nethylarion (
*r)
l l t \ j . i i i J , i
r . l r r STt
/ , - 1s ei
o
i
P E i . e\ chdrged
for frec
scrtne
@sgnrnesi s oF Pr
-
l nost 1' ol
+ cDp- DAQ
-
unus uql
'
C1
:
st cor r c
Oci d
,
C2- Or ochr doni c
aci d
r'
PI
=
rece voi r of a rachi donr' c 4ci d
l '
suustraft oF
pros+qgr24drn sg4tnesi s
-
f ol e of Pt i n. sl gnal fi onsmi sl i on 4 cross mcm brunes
7.
O tP:
. )
w
,-t
Jo
(D
hormone
Dindr 6 6
SPcctFr' c
fC Ccpfor
@ occuprtd
rcceptor Inrcroch
fr
Q+
Prottin
(9
G1 protein
retoscs erDp
q
birur CaTP
4- suboni t
of 6t pr ot ci n
dr socct ot er
4 act i vo+es
phosphcl . l , , ; a
oc+rvsted
phosphol i pose
C
Cl caves
PI
q,s-bfsphospnol c
ft
l p3 I
-
Note: phosphorgtqhbn
ol
pI
produCcs
pA
4rS- btsphospfEtc
l Ps bi hds ER reccpfor
, caus;ng rel earc
ol sequcsi rred
Caz+
Ca" 1DA6
O| ' t \ vot e
, ot
Lret i . l t <, t rt ase
C
PKC catolyzes phosphrxgloion
of ce ulor proteins rhor medr di-c
n5 +Y hormonc
o
\?
Pt'losPhorgtorcd
P
r Otcl ns
@
v)
@
C
DAE
(nre)
celltJ
lqr
responsc
organtc p,pspr'j6
dqrades
-
rol e oF
Pt
i n mcmbro.nc prDti n
anghori ng
.
spccigrt
proleins
can rc
cov oleny oftau1e d ,!;^
catbohgd
rate bt;ry
+o menlbrone bOuM
pr
'
exompl es
of ott acl eO protel ns:
- , r cl l kal i , l e
pnospnot ase: dr ges+i vc enzgmc i n st af t act s
-
cha);nc es fcrase:
enztmc on
pfesynapi . fi enrbfare
whtct,
the nE.
ace\t cholitp
Pnoi Phsl l F, . l sc
c
'
cel l Surface
Pror-ei ^r
cqD aLo l n al tached
+o
gt9cosgl
PhosPhq+rdyl
Inosrtol
@
(qpa)
'
A de
f
i crenc4 i ^ sgnr-nc si r
69 6pt
i n hemo+opoarl -tc
ccl l s
resotti
r' n
hcMol gfi c dtsca<,e*
PAr
o\l snal nocl a)r nc-l hemogtobh\ri a
@;n
+ncsis of Pq E
cardiolipin
-
p6
i r obdi i n Ml ro
chondnol
Merrbfaytes
' -
prc
cvrsor oF cqrdtbl tprh
-
Car di ot i pi n
=
z mol ecul c( ot
pA +
gl gcc( ol
>
Sgntnesl zcd b9 trans
Fcr
of drocyl g l gceroPhos Phdtc frorvr
CDP-
DA6,
tD prcxrsi-inq molecule of Pq
-
PQ
egn*Psi s:
-+
z s tc.p r'*n
frolh
cDp- o
aa
4
9-3-P
Qsg*tfpsrs
o
f
sph'ngo mqell^
-
Found
i n rYEmbroncr oF ncrvc
ttssuc
Pol rYl rtou I CoA
+ scri nc
I
' ^oo*
-\l,
/l \
co, *coo
N ADP+<-
J
s
pn\nqoni rE
' *)l
(LcF^-cD^
-^"*,
"/J\.oo
Nore: DsPhrngo mgel rn
i fl Mgel rhshearh
coni ot i s
Pr t mar
i l ! LcFAr such4s
l rgnoceri c
aci d
{
nsvvoni c 4crd
(a
9149
naner
of broin has
sPhi rgorngel rn
Prrmati l g
contai nri rq
sreor fc
Ocid
ccromi de
I
| /,.-
PhosPror
' d\
I
chohne
I I
lv
I
v
spni ngomgeri n
1-
DAq
@
oegradottbn
of Ph6PYrotiFids
'
Frgorrned
bt phosPnDll'Pases
-
fond
in o[ +lssuer
4
poncreo+rb
lurcc
'
tlsosomt
PhosPvtolrpqse:
spniogo mgennase
@
oegradorbn of
glyc erophospno lipids
'
h\d(Dl\ze
phc6phodlesteJ
bonds
of phosphogty 6er'rdes
'
Phosphohpase!
rereose molecbles thof can
,se rfa as mecsergers
(cx.
on(. { n")
or thdt
qre
subsirois for Sqntncsis 6fi rrre ssengers
(
et. arach;don' c
acid)
Ar o
orz-o
l
J- e,
e.?
i a-o
I
c-e,
cHz- o
t
c
PnoSphol r
pase
O
-
toond
in lyrosoflEs of livcr
t
-
lhtmbroYt bound
PhosPhorglase
phospholr'pdtc
D
pdts
as totrocc l l ul ar messengcrr' .
-
cefofi rbe, thvotvcd In +he responsc to
sfcss
-
sphr ngosi nc:
hhl bi i s pr oi ei n xr hqscC
.
Pnospho
trposo Ar : pr?snr i n mdny i ffmnatti n
ti sgue
-
remove:
spccifr'c FAs
Fom
mcMDrarE- boond
phospholrprht
+
can fcpbce FAs fi ofhd FAs
0sin9
+a\
acgt c&
ironstetulse
.
phospnotrrposc
Az: pfc5en+ i n wny mammal i an ftss.i cs
I pan
grcatrc
j Utcc
X
-
oct s oo Pr t o r cl eose or ochi doni c
gsi 6
-
FnaAttb.
accrc+rbnr
orc r;ch fn prbsctrohirast A2
ptoenzgmc (octirorca bY
fips' n
I
rcqurix
bilc soltr to\
-
inhrDitcd
u1
grucocoricoijr (cr. q9[U:9)
wotrJ
OD
i-
"t
o-
c- tor
in of clos+ridia I otncr
bairtli
c
is acfivarcd by PlP,
systrm
-
pound prtrnorily
in plants
@
OcgraOotrbn of sPhi ngo/hgel ,h
'
spwtgongeniat does fheiob
(
lysosotnal enztmc)
sphtogoncrre l rhasc
sphrngorngclrh
---+--)
Ceramide
-!
phosPhorglcholir
1"",o*iao".
J
sPhrngosirr + FFA
@
Nr cmann
-
Pt ck d r 5e4se
-
Inabrl rfl fo O<grade
-
del i cri n+ enLgftl c:
-
Tgpe a:
(Typcs a
a e)
spngotngetin
Spn, t @amJe
t , t i Qt e
r.lJ-l
-
.t4:
(o
+1pc of
PhosPho' rPase
c)
'
scvcre InFantj l e
forM
'
heporo nl cgal y/ sPl eenomeqal \
'
ropi o
4
progressi ve neu(Ddcgenefaf
on (dcPost+ron
'
' tgve
B:
.
l i Hl e
;e no damaqe of nel Jtol
nssoc
'
4FFech l ungs, sPl een, l l ver + bone maf r ow
-
BDt h
occor W gr eot Er f r gucncy
i n
AshLehoz'
JeN' sh
G l l col i Pi ds
contoi n bottt carbohgdrotc
r l i pi d
derr votir
cs sf ccromides
'
LCFA
i s Otl achcd
+D
omi no al cDhol
sPhl rgosl nc
.
found
in gfeotest amo0nts
,n nc}tol tlssuc
S.Ug$R!9gg\XpJ,9J
arc ctnigeotc: sourcc of Dlood graP aol.' gens
-
cdrbohgdralc
portron
is Onti genic
delettr
nan' r
-
olso scrvg or cell sorface frcepfors
for
toxtns: cnolero 4
tei4nus
of Gal ycosphr ngol i Pi cl s
conloin
PhrsPrrlrc
or
otigo- saccnaridc
airachcd
tp
ceromlde via
O- glycostdtL botIj
of sphi ngonger
l ;., i n)
IrqDUl O+rbn
@
O
Str\J Cl ul e
' do
not
'
tYtono-
@
rcut
rol gltcos
Phtngo
I lPrds
. si mDl est ,
cer c br osl des
-t
cerami d monosdcchori des
fhol ' con+ol i l ei l i |' et
gal ac tose or
gl ucose
'
hl bh con(enfrodonr
of cercbrosi des
tn Drai n +
PNs +
111 abt i n mgel i n shcal h
ccrc broside ( gluco ccrebroside)'
Elobosidc
(
loctosgl ceromioe)
Qloboside ( Forscmon 6nrrgen).
aci ai c gtl cosPni ngol rPl dr
' ngo+rvcri
c6arqca a+
Phtsi ol og;c-41 Ptr
' negoi i vc
due b NANA
i n
ganqt i osi oes
or Dt s0l f of c
gl oup: t h sut f at r ' oes
Ccr- 6l c
Ce r-
C?l C-
(1Ol
cer - 6l c-
( f al -
6ol -
( ?ol Nac- ( f ol Nac
o
O
o angl o sl des
'
verl compl ex
'
found
prrm6ri rt i n gangl i oo cel ts oF cNs
'
q61i v6t wcs
of ccr anr i de ol t gosqcchqr l des
'
contoi n
>
l Y\10\e
cl \es
DF NANA
'
nor
ql - r on: q -
gqn gl i osi de
M, Dr - i , Q
=
one, i wo,
i hr ee, or
f por
Mol e col es of NANA
ex, 6Mz
@ sutgo+ioes
. cer ebr osi des
vi hi ch cont oi n
q
sol f at ed gql qcl o6gl
r esi duc
'
negot r v. t t chol ged ar
Ph! si 0l 0gr c( l l PH
.
rErve fl ss\Je
+
Ktdne' t
@
sgntrresi s 4 Deqrodoti on of
6l )co
s
Phi ng
ol j Pi d s
'
occur .
Pt r mor l \
i n 6Ol 9i
'
sgni hesi s
'
enzgr ne;
9.
1' - 1, ; r . r .
: 1i | r \
i : . : r u; r r !
'
q6d1t r on
of s0l l ot c
Fr oM
6ul f at e
Cor ner : PAPS
-
enz9me: sLJi
' !
i t o, l )
i l c{Ll i ri .
oegr odot rbn 6s6srs i n l ysosomes
@
sphr ng o t i pi dosgs
@
To1- socr r : D l scosc
-
occumul ol bn oi gangl aDSi de. [ gvu)
-
roPi d +
proqressi ve ncuro dcgenerotl on
( or,t) 4
rccrqton sul fqte
\ l t
I ARI .
/' -i \
/ l AR
I
-
lrffo sroroge coused bJ def iciency tn nldrolase
=
sPningo
ltptdoses
O
oM,
qongl i
o s l dDs as
-
o c c0YYrul oi l bn of gongl i oi l des
-
neul ol o9r' c dc teri or dtrbn
-
hcpal o s pl enomegal Y
-
sKel eml deg6r nri tl es
-
bl rri ooess
cJlk"rffl^-p1tr99'9"'
-
l tl !scul ar
\N eoKness
-
s l e zuf es
-
snel l - l i K l ncl usi on
Dodl est "
I
Sqnd HoFfrs D l se4se
-
oCcoryrul Ol i o4 o+
6I{2
r-
gl OboC
-
sa' re hcutol ogrc4l stmptomr O!
@ Meta
c,hroroatic Leuk odysfropny
-
occuMu l ohon og- sul gat r ocs
-
c09nrl -fve
dereri orari oo
-
d emget i not r bn
-
prog res swe po.ral l srs
-
dcMent\a
i n oour+
Eorm
-
Nerves stai n
gcl l owi srr
-
l 2rown
fr
@ For @r
p,g.ot.
' occumul oHon
of ceranl i dc
-
PornFol
t
pro-gressv.
1o!nt
-
suucutqneDus nodoles O+
-
I-roorse
crY
-
tr ssl j ts
sho r\l goonu l omqs
.
-tr#r-
rocs .i-fi
Tr(y-
sqcns,
!$
ft vrsccral involuernent
O FoDrt
p
ricase
-
occumul otron of gl obosi des -
)_l ___l
L
/,
-
r eddr i h-
pur pl i sh sKr h r osh . - - l x- l r nr cdl l
-
Kr dnr \
+
heaf r
f oi t t ur e
/
Z/
l \ \ .
-
burni ng pai n i n l ower eY fi cmi tl ts
@
Caavchcr Dr i easc
\ r r
r -
-
occumul dt i oh of gt ucocer cbt osi des : - f ApY_
-
ryl osl col l tYhon
l tsosornal storage dl seasc,'
t l '
-
hcP4to sPl cnorvl cgol t
-
0sf eoPor osi s
of l on9
bonci
-
CNs Invol very' l cnt i n
rore i nfunri l e 4
i uvcni l e forms
-
+l ssuc
PqPcr
aPPcoroncc OP cafopl osrh
t I OCf O5 b.
Comc engorged
gqi co cercbrosl dc.
@ xtavbc Dl sca6c
(cetoooi a
ccl l Leu|<l )
dystroph.r)
-
o ccuMulotion of g oloc to
ccrebrosides
-
mental
+
molor
deteriorotrbn
-
blrndness + dea
+ncss
-
heqr - f o+al t oss oF mget i n
-
gl ol l oi d bodi es
[
919co
tr' pi d
-
taden
;mri
vnacros) in
whi t-|- mater of br at o
C( csV
I
trel:
vr D
l ei
- l-1
-I AR
I
/
l l
de
fcrnri
ry
l tpi ct tOden
cel E
@
Prosro gl dn di ns + Pel ated cnPd<
'
F'otenr
chpd3
' Pl od0ced
rh verj smol l
qrnoonti i n
ql mosi
otl tr' ssoes rottl ct than r' n sPecri rl gl 4nds
. not
si or ed hovc a shor +
yz- l i Pc
'
mediotd b\ pl0sm0 vvlclrbrone
G- proteins
-
couPled recePlors
O
6gnrhesi s of
pfostogl ondrhs
+
+hromDoxoncs
.
Pfccursor
oi
Prostogl andtns
:
FA' ' l ;nol el c
oci d
-.
efongoted
+ dedarolo+ed
+n
Otqchi d}nic dctd
,
' sgnthcsi i
Of
POH2
oracti doni c aci d
I
ec, n
"on
tnor"
I
J
POHz
/ \
I
throrh bbxoncs
Progt4gl adrnt
'
l sozgme! o+ POH Sgn i hqse
-cux-r
t
cox-2
-
cox- |
' const i l ui i r i cl y
n4ode i n
mosi
+l r su"r
'
mornl enonce of hcol tny gqstrr' c l -r!suc
,
ren4l hol hcosf4s ts,
Pl atcrer
aggre9at1bD
-
cox-2
P(?H=
Prostag
l ond i n endo
Ffoxi de
' ER
mcmbronc
-booM
enzgrnc
.
2 cotqtyfi b o cti vi
+es:
O
faHy
qcid
cgcto ory
*nas
(.ox)
-
re4uircs 2x 02
@ peroxr'oase
-
dcPendcnl- on
rcdttre6
gluto+iionc
'
f ndoci
ble bg Ac+warc.a [Anunc o-nf lamnatnr! rcspone.
'
fi edl afcs pai n, heat,
IEdDcsl r
sMctl ;rg,
Feve(
'
i ntri Or ti oo o
f
pr osto
9l andrn Enrhcsi s
-
corrri ol i nhi brts phosprrot' pase 42
L+ .. no Orochr
doni c add
-
n? pfost^gl an&tns
-
cspi rrn
,
r4do
ffefi l ari ' t'
Phcngl
Duruzone
- l nni Di +
ao"-,
4
coY-2
-
cefccoxi b
=
ti thi Oi + cOX-Z
@
sgnrnesi ! of l euko
tri enes
-
I l Dt ar
hgcr t oPer ox9
acl ds 5- l r Pox
ggenqs
e
' i n
ncut 7ophi l f
A rocni don rt oci d
I
I
|
5- l r Pt ' xqgenose
I
I
.l/
5- HPTF
-----------J
ltu kot reieTE.
-
l c! Kot r i cn. s
"
Me Cl r Ot Or s o+ oI Cr gi c
r e6ponsc
4 l nFl qml f l ah0h
-
Inhi Di l ors
of 9- l l Porggen4se
+
l evKo' rr' rc.).
rcccPtpr cntogonri i ' r
=
ffeaiMrnt
o+ 4 Slirna
@
Rol e o+ prostoql ardtns i n
Pl ol -el et
homeosrasts
-
ovor
rqn r' utcri ne
tuncti on
-
bonc mc tdbol i srYl
-
nerYe
+
broi n
l uncrrbn
-
Sntoo+h
muscl e rc gol ai i on
-
p l Otel e
t ho$l co Stas
i s
'
Thr ombor one Az
[ - f
XA2)
=
Pr o
duccd bY o' ' t l va+d
Pl at e] et s
-
pr
on4otcs 0odherencc I o99re gOtton
0+
Pl otel ets
@ conl racl -i on of smooth Vqsc0l ar
h0wcl e
. . . ^ - . \
'
r r o' - t qcgcl r ^ ( r qt 2,
-
Prodvcco
D! vdscul af
ando-thel l 4l cel l s
-
l nt i l bi t JoPl ot t l er aqgrcganon
I causes vasodi l al -ron
' t
tttt&der
+hrambogenes' s
' aspi r r n:
i nr i t bt +s 1xg,
chol csterol
+
stcrol Mcrqbol rsl ,l
-
Chpferl E
' pl qot
st er oF bl ock abJor Pt l 0n oF dl et ar Y Chol st ef ol
t5
dretqr\ i fedtment
oF i Vper chol csrercmta
' Pl ar mo
chol er t cr ol
- -
est er l ed
F0( r | 4
b
chotesrergl esters
--
!!I founa
ln mernbrancs
@
sgnrncsts oF cholerterot
.
occurs In ol l ttss0es
, '
ql l
Cr s
Fr oM
ocet ot e
'
NADPH provti l es
radtrci nq el ui votents
.
sgnti esrs OCcUrs rh
cgtopl asm u
O
c! tosot
@ cJrusol i c Mml trone oF FR-
HME- Cl A
2rNADpH
-\l
HM(r coA
o)l
"'ouc+o""
2r{ADp+
r' $rr^
Mevol onl C
Acl d
2x AcctJ l - coA
o
|
' ' "' u' o' "
^JI
Accrcqcerul
-
coA
o
@
Fote l i yyri tl i ' g +
fegul o' l org
steP
-
i rrcversi tl c
-
fi M(r CoA redoctase
-
Mcmbrone
Prorei n
i n ER F enzgrhai tc
domol n
Proj e
ctri l g Into cfl oPl osM
.
o b\t
cholesrerol
^"?J;
-)l
n^no .,^
,oo/
|
6gnl hase
@
Lr vcr por enchyMql cel l s
ho. vc
2 i soenzgmC4
of HMc? CoA sgn+nasc
.
cgtosol ,c enzgM
=
cnol estcrol sgn+hesi s
.
Mrtpchondri o,l en4Me
=
Ketone
bodq
sgn esi s
, ^ ' " - \ |
@l
I
r' "oses
zev </
I
ADP
isomerote
5-
Pgr
ATP
ophosPro nlevqlonic ocid (e c)
t;
I
o..o,ro,r,o..
-F
co2, Ps
t Pp ( Ec)
Mevol ont 6ci a
(ac)
formol i on
op
farncsg
t
-@
'
Covolent
o+lochrYlent oF
tqrncsgl
proter' ns= "prengl q{on'
@
9e
2r
'
(ec
Tronl
!-
P
( o
pc)
r nS
" P
I PP
rose
Pi,
I
l-!
99
1 |
rrq.5
g..o"e
ql,
Js
"Pi
FPp ( l 5c)
6quo.l ene
sgntnose
\
*, 0,
a\
NADgt
squqreOe (600)
sq.uolenc (Soc)
--..
l/""
@\1,
*4i*:""
I
Monor99enose
NADPH
NnDP+
uonosterot (aoc)
I
@
lra
at F ferent
i
tn'9ttt
cnoresterot (zeC)
@
Smri h
-
Leml i - opti ? Sgndrome (sLos)
- AR
' def
i ci enr emgfi e
I
-7-
de hgcl rochol cs
i crol -
+-
red octuse
-
enzgtylc
Invotved in ruigrotion
of dblc bond
@ Rcgototi on oF chol es tsol sgnrhesl i
.
contmr pl
=
rarc- l i mi i g HMq CaA reductuse
O
stcrol -dcpndent fegul ofbn of gcnc
fegol oti on
.
SPEBP
-
rotr4l mcmbrane protetn of ER
-
Ossocl otcs W 2nd eR
mrnbrqne
prbfel n: SCAP
-
tronr
-qchhg
TF +rO f
bti l ds
ctt-actrng sRe
eEmenr-on DNA
.
lD\t srerol leve ts
_
scnd sRFBp_scaP comPl er t o
6oi
-
9c
ts sol ubl e
-
Frogment ften goes fb n0cte6
4
qcts
os rF
-
I HM6 CoA redUC+Os e sgn+hesi t
=
l chol estqol sqn*rcsi s
'
hgh srcrol l evel s
-
r ct cnt l on oF SpeBP- scAP col nDt cr
@ stcrol - o ccel erqi -ccl enzgmc
degnrd6trbo
-
I l cvcl s of
.stcrol C4usc cnzgrrc
rcdr
ctose
ro
ondcrgo trbi qOi trhotr6n
--
degrodotlon
O s+erol- Ind c
Pend
en-t phospndg ntl'01
ldegrodon'on
feducl ose
octrve
phospnofase
HM6 COA
fcductase
tnoc+rve
@ Hu onal Regulqttm
-
ti OSr_rtri r
-
t nUO coAredocts.se
-
f
gtr;C-ogon
=
J'
dMQ
CoA reouctqse
@ lnhibirrm
t1 drr-rgs
-
(evc
lsibte
,
compe.$trvt inhibi+ion of HMq crA reducta
se
' ot or va! mf i n
' f l uvost at t n
'
lovos
t.dfl'n
' pr ovqst oi t n
'
rosu\,, a stdt-ln
.
simvastanh
-
.1,
pl osrno
cnol eri etol l evcl s
rh pts tF hyper chol c sl .ercmra
@
eegraaa+ton of chol esrcrol
.
Cholcstcrot cqnnoi te mc
.|abotlzed
-to
CO2
+
HzO
'
el rmrnod
ttom
body bt
conversrDn to
bi l e 6gi g
1
bi l r sd tts
@
ei t c 6a161 + Bi l c, sot r
.
woterv hi x tufe of
or gani c + l nogqhi c cmpds
'
most rrhpoftonr cofi pDnentt oF bi l e sat+s-
phosphot i dvl chol i nc (tecr+n,h)
+
bi l .
s4l ts
@ strucfure of BAi
. 2+C\ !
t - 3 OH
gr oups
,
si dc chot h
f t l r r t
i t ' mr r o+ei
as COoH
.cooH
pKa'
6
,
r.
not
forty l 6pri cd
@
physi otogi c pH
'
Pofar
+ nonPolat
face
6 sgn+nesr! ep 6ni
.
syntncsized in tr'ver
'
ftorf common' choti c oci d
(trrbt
)
* chenodeoxg
chottc
aci d (arbl )
ctDle lcrol
cnol est-ero\
-
+-
(-
hg droxyl ose
'
fote
-
ri mi ti n4 step
cnolcsrerol .ER
Ossocldted
c,gioch
fome P+6 enzl,nC
l-!(- hgdrorqiase .
ryry
togO
in tiver
' O
c not i c oci d
O chol esttrol
chollc ocic
squotene (eoc)
--,l/"'
t)la-
""o
1. . f
squot . n.
l rn"noxgge' . ' os'
o
NADPH
NAD P'
uonosterol (3oc)
I
@
l 7a
cl i t
l erert r
Y
enzqmcs
J
cnoresterot (z+c)
@
Smr +h
-
Leml i - Opt i ? Sgndr ome
( sLos)
. AR
' defi ci cnt
cnzgme I
-l -
dehgdrucnLl csrcrol -
+-
red ucmse
'
enzg\c
rnvotvad rh nrigroion
of dblc Lond
@
Rcg0l oti on
oF
chol es tcrol sgnfi esl \
'
cofi rDl pt
=
rarc- l i ntni g HMQ c.o4 | eaLctQsz
(D srerol -dcPendeni regul otton oF genc
fegul oti on
.
5PEBP
-
Integfdl mcmbrdne protein op ee
-
qssocloler
w znd ER ryEmbrqoc
Frotrrn:
scAP
-
trcns
-octr'ng
TF +ho t
brilds
cis
-acilng sRe etcment on
,
lorN srerol leveF
-
scnd sRFBp- scAp compl er i o
6ogi
-
9
ts sol ubl e
-
frog6ent filen gocs fb n0cteL,s
*
Oct 6s TF
-
1 HM6 coA reduc+ose sgnrhesri
=
165s1g5tcrol sgn*rcsi s
'
hgh stcrol l cvel s
-
r ct cnt t or l oP SpeBp- SCAP compt c' .
@ s
teroF
q
ccel crqt' ccl enzgmc degrodorl bo
-
I l cvcl s oi
.stcrol AuSe cnLgl Ac
l ,dtJ
ct^se
fO
ondcrgo Obi qul tl noHon
--
degrqdotron
@ stcrol- IndcPendeft+ pYlospnofg lotlcn
ldegrqdotlon
feducmse
octrv
phospnot ase
HM6 COA
fcdo ctuse
l noct rve
@ normaql Kegul4nm
--
t i nsutrh
=
I Huo coArcdactase
-
I
grtrcogon
= .1,' HMO
c-o
A req 0ctclge
@ Innrbi trm
e
dl ugs
- (evc
fsible
l
compe.trtr'vt
(nhiottion
of HMq CrA feducl-a se
' or bt vost qf l n
' f l uvost ut t n
.
lovoS
t-dr-ln
' Pf ovqst qnh
'
rosu! o sl-dfl l'l
. si mvasf ar t h
-
l
pl asmo
cnol eti e/ol l cvl s
rh pts. fl hyper chol csfercMl a
@
eegraaaton of chol csrol
'
cholcsferol cqnno+ be *g
1469llzd
+o coz
+
HzO
'
elrrylnored
trom
bodl bl
conversron fo
oile 6";*
I
bile so ns
@
Bi t c ocr br + si l c sans
.
Noter! hri t l ure of of gqni c + Inog4hi c cmPds
'
most tnl portahr Conponen15 oF bi l e sal ts-
pho
sphot' d\,l chol i rr
(l ccl +nrh)
I
bi t.5o' ."
@sructure oP eni
. 24CBr
t - 3 OH
gf oups
,
si dc chOr h
f hat
+t l ' r r no+e!
4r Coof l
'
coott pKq- 5
,
i.
hot
Frjrt! rbnried
@
physiDtogic p H
'
Polar
+ nyPolar
f<ce
@ sgnrYPsrs ep 6a3
'
sgn+nc sized in tr'ver
'
fros+ common: cnol i c oci d
(trrbt
)
+ chenodeoxg chot,b
aci d (drbt)
cnol esi erol
-
+-
(-
hg drox9l ose
'
fote
-
limitinq sfep
'ER
Ossocloted
cglochfome P+fi cnzgt]F-
.
6nry
to15O
rn liW
. O
cnot i c oci d
.
O cholesrcrol
C lDle slcrol
I
I
cYl ol csrerol
|
1-4- hqdroxqiase
I
I
clr)llc octd
@
sgntvl csri oF bi l r sol ts
-
bi l e octds cOn-J ugofed 1D taurl ne or gl ycri ?
-
r or r b of
gl t ci ne: t qur i f f i s 3: 1
-
bi l t s6115 ore eFFcci i Ve dercl gentt Dl c qhl pi po+hi c
notorc
-
boc-tcflo in In+esirne
flora
6ap rcmove gllcio.
or toorinc
,
fegenentirg rnc
@
Emerohepant crrcolqtlon
-
bi l c
sal ts
- qsl .
reql rf
OrEd by mW oSol Ccl tr i n s.T,
o
EA
6A
J
f
9l t ctne
+
qu
t lt\e
s.r. (i l euM)
trLORA
BS
--------+
f'nuc
os ol
- - - RA
a
tsA.J
o' sg ex cprcd
?
{,
cel
l s
qSl . f cobsor bed
'
Ohol estYfqmrhc
-
prevcni reupraEe of
freotMenr of hlJper-
cr0l esl cr0l cmr4
e Bi tc sort def rci coc.\,
:
chol cl i i h' asi s
.chol est6rd
gol r srcne dl sedse
'
cqused b1 J bA th bi l e '
vrh' bh
maY
fes0l 1
fro
:
r.
mol obaorpttbo oF BAs i n SI
2.
0bS rrctl on Of btl i ary trqct
3. hcpotl b dl sfuncton=
J sgnth.si r oC Bs
tt.
ercessrVr
tsedbqcK
soppressi on 0f BA Egnfl esrs bl c
1 rOrL oF reabsorphbn
of tsA
5 1
btl i orl chol csterol
excrctl 0n bl c of
fi brdi rs
.
Gcm fi broai l
(
f,i brote)
-
U TAo
l eveK
;n Uood bY uP-rc-gutai l on
BA bt 4l ucosol cel \s
i n got
L wcr
I C- 1 UO
of
B
-ox
' d at"n
@ Plosmq
ltiro prDtcin!
' sPhcfi col
mocromol ecutqr CoYYl Pl ercs
of
l rPl ds * spcci prt proterhs
.
I rpo protern por
ttdl er: chtl omi crons
,
VLDL,
LDL
I
H DL
-
diPfer rn:
O
Ptot
cin comPosinin
@
stzc
@ denstlY
@
sftt oi origin
-
fonctton'
' t r qnspor i
r i dds
.
rnqre lipidt nol\jblC
-
d\sf oncfi bn
.
norrowi ng Of B\f
=
ofhcroscl etos,i
@
cowrpositrbn of
dosmo
tipoproteins
-
polof portlonr
otc cxPoscd on
s0riacc
-
size
+ dcnsity o1
lipoproteins
-
qpol i Proprorei ns
'
scTvc 05
fecognrfl Dn
s
' dr vr ded
Dl St f u chj r e
+
-
APo A-r
-
Apo C- l t
dcns
i t 1
ri s
ftr
cel l -
sorfoce fccePbrs
f unc
f i on I ni o s
nqj or
cl osses;
A- - E
si l
e
c hUlomrCrons
V LDL
LDL
hDL
@ Metanot,r-
oF chyl o/r4rcrous
@
' 0ssi nbl ed
i n r' ntesi i nol muc0l ol cel l s
.
COYI \ :
_
dl et ot )
-I AEs
-
cholcstero)
-
Foi -
sotubl e vttomi ns
-
cholcsl-crgl esters
u
=
nonsense
codion
-sgn+hrsr!
of
oporl poprot et ns i
o*
-
Apo 6- +8
=
chglomtcroos
\-/-\---,.'--\-/
8
-gcnc
+
sgnrhesi r btgi nr on ree
<-- 4A+
-+
gl \col gl orrd
fron
Ee to
q69i
J
-
Apo B- r oo
=
VLDL
+
LDL
+
i n t wef
'
ossemblY of
ch.,tomicrons
<- 10o. , .
-
mrcrosonnt rAo ffonsFer protei n
:
l oqdr opo B-4S
f, frpi d
'
opo c + opo E ore odded
f-rom
HDL
NOi e:
. qPo
C-4 r' s nccessarq
f or
qct t vonon o+
-?
occors be
fore
flonsrtion
irorh
eR
-.
eolgi
'
l ttod
' s
of
nosceni chgl omtcronl
-
v,)hen Chgl oMtcf
On teOChs
bl ood pl aSma,
ItPoProrern
tiP656
' qPo
E=
fccognized aJ beq+1a re cepfofs
' degrodot i on
of
TAq b' J
l i poFot ei n
l rpose 1uerl
-
LpL is onchoted
1o cap tary wolls of rylost tlrsucs
Dl'
\kR
gl^ttl&{fu
+
mosf l t i n od, pose t i ssuc, cordrbc
+ SKcl cml
m
-
odul+ tivef dDes nof nave this nzgrne
-
ir\cr hos hcporic lllxrse o llac ks
cnglomtcron
o( \LDL
' rtEs
'
del i t i nc4
o{ ' , , ' r , , ; ' l ; Pase or
4pe Q- [
=
'fgpe
X hypcr lipoprofcin erwe or
fonil,at
6rorion rh rppasc defiacrrl
'
rrgul ot i on of l i puprot ci n I l pose act t vi t V'
-
sgni hesi s Srrrnul Ot ed by
, n\ Li , ; J
-
<.,drpose l rPorDrotei D
t;Pase
. l or gc
Km
'
removol of FAs
from
Plo(11)4
-+
TFIc"s
-
hcor t muscb
l l pogor et n
i l Pqso
.
smal l Km
'
Use
FAs
.
tormol i on
of
Cngl omtcron l rqnonts
-
os Chgt oml ar on cr r cul ot es
r
l ot cr >qor '
' TAqc
- qPo
C i s rcfurned to
xo|-
a
remorni og
Pdr
hcl e rs col l cd
' ttmmnt'
-
oPo E
rccognrzed bq l l ver
=
rcmoYed
l rom
ti i col o+tcn
@ Met o bot i sm of vLDLs
.
mode i n LrveR
'
corrl
llpid
from
liver
lo per rplpr4l tlssues
-
fi yl bol qncc DIA/ l tvar
TA6 sqnthcsi s
+
secrenon of VLDL
=
heponc s tea los is ("'1atry rivu
')
'
secretd driccttg
IntD b{md
'
new VLDL hAve ts' l oor must Obrai n C-4 +
opoe
l tom
HDL
'
defct in mrcroscfilol
'rAb
ffangf<r
Profein
=
n ne{o lr'poproteincmr'e
->
cannot toad aPo
B N l rPi d
.:
,O VLDLS or Chgr'miclorr6
'
As VLDL
crrcul otes ,
TA ca degroded b\l
l i pbProfci D i ' pose
=
{ si ze +
? densri g
+ opo F {
qpoc
returned l o fl DL
--+
TA(?s fronsFqfcd
i tom
VLDL-=r
HDL
.-:r
somc Chotesl rul
esters
ffom
HDL-;
VLDL- Dy chol esi Igl
esi er
tTOnS
Fcr
proicin
''.
lrDL is
eR0vf,It\fl
+D LDL
-
d ur
l ng f l onsl on \ I e
gcc l DLs
-
lDLs +qKen
uP
b\ cells fhrough recc
P' lo-
medl4ted endocgtosis +hdr
uses
oPo E os l l gdnd
Nofc; homoztjgores
for
opoE dcfirrehc4 can46+ cleat
le rnnan'' Df
chylDmlLrorK 0r I DLs
b tgp" 1rl hgpet lrpo pr ofJDcmia
(Broad Betar
cltsease)
@
Mctonotism
o+ LDLs
.
LDLS
=
J,
TAq
l chol cs fcrol
+
chotesrgl
esters
-
Pfovides
Cholestlol iD
Ferl
pneral
+lssuas
--+
mcC,ft-On rSm?
( oa
--r
LDL
recptors on cel l s recognrze qpo
b-l oo 4
qPo ofl LDL
Chol esrcrgl
estr
aPo
B- ' , 00
Coql cd Pl t
c tO iir
rh
Cl q-thri n
.
Stobl l i "er shope oF prt
( , LDL- r eccpl or conl pl cx t s t nl t l nA Zed
foncfl
onol
LDL recePtor!
h9
Per
l r' pl demta
vcsi cl e l oses i ts Cl oi hri n
66ot
{
fuses
Nrth
6i her vesi cl cs
torrn;ng
endosornc
pl t .t, bi c
of ATP4se
' cquses
separo tl 0n oF LDL
troM
rcccptr
' st l uct ur e=
c0RL
rccePton
=
recgcl ed
l i pop rotei n +ronsFerred hc l ysosorxe, rel ease!
.
Fr ee Chol es
t r ol
.
o nri no aci dc
rlSoSome
FAs +
pfl ol
Phol l Pl ds
Connot hgdrol gze l ys0sorfpl Chol e
si uy) srcrs
=
WOl rn4n dtse4se
connoi r ansgr
chol esi cr ol
or Jt oF l gsosor he' Nl emann
- Pi ck
di easc
, ' f ype
c
chol $+erol norneostosi !
-
oPtaKe of chol csterol oFFecfs
cel l fn scver4l drFF. Waysr
O l
fchOtestcrotl
=
i nni frrr6n
of
i 1f.)(i LaA re:-.:..t.1:,:.
@
? [chol srcrd]
=
+ f-OU recephr
s9n+hesrs
O
Chol est er ol
- - - n+
ehol est er gl
est er ( st or ed i n cel D
- t
L,
' A';
.
opi qK of chol est erol bg mocrDPl l o
gcs
-
vrb rccePtor
scavcnqet fcccPtor
class a
15c-r)
-
Note, rc ceP+ar ri nol- down
reg0lotd euen it I
fchote
sttrotl
:. gggomgl si on
0f Chol esrcrq, esrers
=
hfoah
Ccl ts"
def r cr enq of
=
1-9
Pe
11
o
Gr
\3'_
I
v
L>
atiero scterott.
Plaxtp
o Metobol 6nl oP f+DL
' f or med
i h bLooD
.
oddi ti on
oF
opo A-1
-
oPD A-1
mode th l rver 7
=
To.t. of
apol i pDptoJei n
con+enI
i ^ Hot-
'
scr vet qi q
r er evoi r
f or
6Poc{ + Apo E
.
newl y made tr DL
=
di s
l c shoped
-
cont oi n: phosphol i pi d ,
qpo
A
I
C, E
,
Convcrted to sphcr ico'l pofitcks r/'Jhen il,eV o ccumolqtc croles farol
' os
soon
qs
HDL
t dKes 0p chol er r cr d, i r t !
est cr i pl ed b\
pcAT
chol e sterol
' Pc
donor cs o FA Fr om
cz
-
Chol esrcrol
l s foken
fro/Y' :
A Per
iP\tctat tlssler
----t
-
HDL t hat f q( cs chol est cr ol r o l t ver +
sf er ot dogenl c cct l s
=
l l DLz
-
r et cOse of l r pi d- depl eFed
HDL
=
HDL3
-.
chol si erol r! tooded on+o t-rDL bg the hel p
o+ ABcAa protetn
--r
def rcl encg of ABcAx
=
-l ongi er
di ease
=
obsenEe oF HDL bl L degmdo+r on of
l l pi d
' poor
Apo a- 7
-
oP}aKe o+ Chol es
tenj l
esrcrs b9 ti ver
ta; 5P-131
recep+ors
t ipoprotein (o)
,
Lp
(o)
--
r{ prcsent i n l arge quonri rr' es
=
f |sk of coronorg
Ho
-
LP(4) i t cDval ch+Ig
,rDked tD qpo B-l oo
-
1 LpG\
=
Jl ows break down of btood cl ots
-
t!+
nelrt o*:,ac<
f
Pho5
Pnond.g
l chorrne
?CAI
cnolestergl-
estor
l yso
phospho t t d! l
chol l nc
'
rcverse
cholcsierol tronsPort
l yso
Pc
bi nds serorn
ol bumi n
in
blood
lrlasma
ro be
fionsrJorted
u n,
,,
ttu"t
t
blle sgnficsls
-
Steroi d
ogeni c cel l s
I
hol monc synfh6' s
Steroid
holmoncr
cholcsrerol
=
Prccursor
of alt
ol s
closse(
oF sierold hof molrs
@
' desmol ose
-
bcl ongs tb c\P prot' n
Fami l Y
-
i n thc i nner Mt+ochondri 4l
nleffDrqnf (rMM)
-
movchl cnt Of Cho Estfol
Into
fyl l fo.
-
conhrol p.i .
-)
mcdrq+ed bY StAp
Prcgncnol onc
I
.f
.t
steroid hormoncs
con gcnit4f 4drenal HgPcrPlas|ns
ccAH)
Pregncnol one
1
@
def rci cncg I n t hi i enzgt ner
g
{
s?- ngroxgsteroid ou no srcroid
hormonra producion
-
|
'
solt cxcre tion in ori^
w
'
Pts
hove
tcmal e
-
l l kt geni fdl p
ProOcier0nc
' ,
\
|
\
@6sgi ci cncg
i n +h(s enzvmel
@
j ( ' t-
4- l -tgd
yoxy
l ose
'
no sex hormones or cori i sol
-
| \
' i
prod
ucti on ol Mtnc ra
l D cor tl coi ds
J
\
=
No+ rctenrl bn= hgFr+cnsr;n
t1- ,{- Hgdroxgprogesterone
\
.
pt.s have
fenrle
liKe genr+atio
rl
.t@
lr
u '
-
"-:r*goo
r,gn,"f
VJ
ll- Deorgcortlsol ll- Dcoxg cotl'l cosierorD
?= mosculriotron ot
/
e\lxrnat gcnltdta
@ a"l tc,rri ry rn thi s enzgrnc:

'
ovcr pro dr cl -ron of
qndrogentt
O"=
-aorl y
'
most
conmon
form of cAH
vi ri l i zarl on
.
clossic
form:
qbsencc
of mrne,dto- + gl\co-
corticoidt
.
non- cl asst L
por p'
def i cr i ncj of Mr nar al o
+
9l Dc0- cor f i cor ds
Dcox9
I
T
J
cortl s
@ secre+i on of
qdrendl
Cortrcal steroi a hornl on.r
A cor, i "'
-
Made i n zona
fasi col o+a
(mi a6te l aygl )
-
hgpo tfDl omus
+ cRH
-
Prt .
gl ond -
o. T
)
ddtcna I cort-et

r el case oF
gt ucocor t r cor d
Cor t i sol
-
Ol l o$,s body +o
fespond +o srress throqh i |3
"pta"r
On tnre( medtarg
mcrab}l;m I
nf launar\t
j
respltr;e
' A'
Ac' rH
WorKs
throug^
iffi7.F^1fr$il
@
Al o..s tt t ,-,-,..
-
madc i n zona gl on)cru l 0so
(otri ar l orcr)
-
l . \ duced bg . L
i n pl asw Nar l ka f al t o *
\
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