Biomembrane and Cell signalling
BCH 452(Biosynthesis of Cell
membranes)
Dr. Samina Haq
Dept of Biochemistry
King Saud University
Synthesis of phosphatidate
• The first step in the synthesis of both phospholipids for
(diacylglycerol
3-phosphate).
membranes
and triacylglycerols
for energy storage is the
synthesis of phosphatidate (diacylglycerol 3-phosphate).
• In mammalian cells, phosphatidate is synthesized in the
endoplasmic reticulum and the outer mitochondrial membrane.
It is formed by the addition of two fatty acids to glycerol 3phosphate, which in turn is formed primarily by the reduction
of dihydroxyacetone phosphate, a glycolytic intermediate, and
to a lesser extent by the phosphorylation of glycerol. Glycerol 3phosphate is acylated by acyl CoA to form lysophosphatidate,
which is again acylated by acyl CoA to yield phosphatidate.
• These acylations are catalyzed by glycerol phosphate
acyltransferase. In most phosphatidates, the fatty acyl
chain
• attached to the C-1 atom is saturated, whereas the one
attached to the C-2 atom is unsaturated.
Synthesis from an Activated
• The de novo pathway starts with the reaction of
Diacylglycerol
phosphatidate with cytidine triphosphate (CTP) to
form cytidine diphosphodiacylglycerol (CDPdiacylglycerol This reaction, like those of many
biosyntheses, is driven forward by the hydrolysis of
pyrophosphate.
• The activated phosphatidyl unit then reacts with the
hydroxyl group of an alcohol to form a phosphodiester
linkage. If the alcohol is serine, the products are
phosphatidyl serine and cytidine monophosphate
(CMP).
Synthesis of Phosphatidyl Inositol
• phosphatidyl inositol is formed by the transfer of
a diacylglycerol phosphate unit from CDPdiacylglycerol to inositol. Subsequent
phosphorylations catalyzed by specific kinases
lead to the synthesis of phosphatidyl inositol
4,5-bisphosphate, an important molecule in
signal transduction.
• 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
• phosphatidyl ethanolamine can also be synthesized
from ethanolamine through the formation of CDP
ethanolamine.
• 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, CDPethanolamine.
• The phosphorylethanolamine unit of CDPethanolamine is then transferred to a diacylglycerol to
form phosphatidylethanolamine.
• In mammals, a pathway that
utilizes choline obtained from the
diet ends in the synthesis of
phosphatidyl choline,
• The most common phospholipid
in these organisms. In this case,
choline is activated in a series of
reactions analogous to those in
the activation of ethanolamine.
Interestingly, the liver possesses
an enzyme, phosphatidyl
ethanolaminemethyltransferase,
that synthesizes phosphatidyl
choline from phosphatidyl
ethanolamine, through the
successivemethylation of
ethanolamine
Sphingolipids Are Synthesized from
• The
backbone of a sphingolipid is sphingosine, rather
Ceramide
than glycerol.
Synthesis of Sphingolipids
Disruption of Lipid Metabolism
• Respiratory distress syndrome is a pathological condition
resulting from a failure in the biosynthetic pathway for
dipalmitoyl phosphatidyl choline. This phospholipid, in
conjunction with specific proteins and other phospholipids, is
found in the extracellular fluid that surrounds the alveoli of the
lung, where it decreases the surface tension of the fluid to
prevent lung collapse at the end of the expiration phase of
breathing
• Tay-Sachs disease is caused by a failure of lipid degradation: an
inability to degrade gangliosides. Gangliosides are found in
highest concentration in the nervous system, particularly in
gray matter, where they constitute 6% of the lipids.
Gangliosides are normally degraded inside lysosomes by the
sequential removal of their terminal sugars but, in Tay-Sachs
disease, this degradation does not occur. neurons become
enormously swollen with lipid-filled lysosomes