BIOSINTESIS LIPID MEMBRAN

Meta Kartika Untari

 3 komponen penting penyusun membran-membran
biologis :
a.Fosfogliserida
b.Sfingolipid
c.Kolesterol
 jalur sintesis triasilgliserol melingkupi proses biosintesis
fosfogliserida
 Kolesterol berperan sebagai komponen membran dan
prekursor dari macam2 molekul pemberi sinyal
Hormon steroid (progesteron, testosteron, kortisol)
berasal dari kolesterol
Fosfatidat : zat antara pada sintesis
fosfogliserida dan triasilgliserol
Jalur sintesisnya dimulai dari gliserol 3-fosfat, yg dibentuk melalui reduksi
dihidroksiaseton fosfat dan sebagian kecil dari fosfolirasi gliserol. gliserol 3-
fosfat mengalami asilasi oleh asil KoA, membentuk lisofosfatidat, selanjutnya
mengalami asilasi lagi dg asil KoA dan hasilnya fosfatidat

Asilasi ini dikatalisis oleh gliserol fosfat asiltransferase.

 Sintesis triasilgliserol, fosfatidat akan dihidrolisis oleh fosfatase
spesifik dan dihasilkan diasilgliserol (DAG), selanjutnya DAG
mengalami asilasi mjd triasilgliserol dlm reaksi yg dikatalisis oleh
digliserida asiltransferase.
 Enzim-enzim tersebut bergabung mjd kompleks triasilgliserol
sintetase yg terikat pd membran retikulum endoplasma.
 Sintesis Fosfogliserida secara de novo
• Diawali pembentukan diphosphodiacylglycerol
(CDP-diacylglycerol) dari cytidine triphosphate
(CTP) dan fosfatidat
Unit fosfatidil yang aktif bereaksi dengan
gugus hidroksil suatu alkohol yg polar
In bacteria, the decarboxylation of phosphatidyl serine
by a pyridoxal phosphate-dependent enzyme yields
phosphatidyl ethanolamine, another common
phospholipid. The amino group of this phosphoglyceride
is then methylated three times to form phosphatidyl
choline. S-Adenosylmethionine is the methyl donor.
• In mammals, phosphatidyl ethanolamine can also
be synthesized from ethanolamine through the
formation of CDPethanolamine. In this case, the
alcohol ethanolamine is phosphorylated by ATP
to form the precursor, phosphorylethanolamine.
This precursor then reacts with CTP to form the
activated alcohol, CDP-ethanolamine. The
phosphorylethanolamine unit of CDP
ethanolamine is then transferred to a
diacylglycerol to form phosphatidyl
ethanolamine.
 Sfingolipid disintesis dari seramida

Enzim yg mengkatalisis reaksi ini memerlukan piridoksal fosfat

 Gangliosida merupakan sfingolipid kaya
karbohidrat berupa gula bersifat asam

• In gangliosides, the most complex sphingolipids, an oligosaccharide chain

attached to the ceramide contains at least one acidic sugar. The acidic
sugar is N-acetylneuraminate or N-glycolylneuraminate. These acidic
sugars are called sialic acids. Their nine-carbon backbones are synthesized
from phosphoenolpyruvate (a three-carbon unit) and
Nacetylmannosamine 6-phosphate (a six-carbon unit).
 Sintesis gangliosida
• Gangliosides are synthesized by the ordered, step-by-
step addition of sugar residues to ceramide. The
synthesis of these complex lipids requires the activated
sugars UDP-glucose, UDP-galactose, and UDP-N-
acetylgalactosamine, as well as the CMP derivative of
N-acetylneuraminate. CMP-N-acetylneuraminate is
synthesized from CTP and N-acetylneuraminate.
• The structure of the resulting ganglioside is determined
by the specificity of the glycosyltransferases in the cell.
• More than 60 different gangliosides have been
characterized (see Figure 26.4 for the structure of
ganglioside GM1).
Synthesis of Sphingolipids. Sphingosine is converted into
ceramide, which is an intermediate in the formation of
sphingomyelin and gangliosides.
 Synthesis of an Ether Phospholipid.

• Steps in the synthesis include (1) acylation of dihydroxyacetone

phosphate by acyl CoA, (2) exchange of an alcohol for the carboxylic
acid, (3) reduction by NADPH, (4) acylation by a second acyl CoA, (5)
hydrolysis of the phosphate ester, and (6) transfer of a
phosphocholine moiety.
Platelet-activating factor (PAF) is an ether phospholipid
implicated in a number of allergic and inflammatory
responses.
 • Plasmalogens are phospholipids containing an a,b-
unsaturated ether at C-1. Phosphatidal choline, the
plasmalogen corresponding to phosphatidyl choline, is
formed by desaturation of a 1-alkyl precursor.

The desaturase catalyzing this final step in the synthesis of a plasmalogen is an

endoplasmic reticulum enzyme akin to the one that introduces double bonds into
long-chain fatty acyl CoA molecules. In both cases, O2 and NADH are reactants, and
cytochrome b 5 participates in catalysis