Glycerophospholipids
diglyceride-based lipids containing a phosphate group and a small organic molecule (usually choline and ethanolamine). Exception: Spingolipids
Sphingosine
contain a phosphate group and a small organic molecule, the backbone is sphingosine instead of glycerol
Phospholipids are used to form:
a biomembrane bilayer: has an inner leaflet and an outer leaflet
What are the four aspects of membrane heterogeneity?
(1)The phospholipid composition of the two leaflets of a single membrane is different (asymmetric distribution), (2)The phospholipid contents of different cells are different, (3)distinct lipid composition of various membranes (e.g. ER, mitochondria, and
Explaine the asymmetric distribution of phospholipids in the two leaflets of membrane bilayers
Outter leaflet is devoid of phosphatidylserine, and rich in sphingomyelin and phosphatidylcholine, whereas the Inner leaflet is rich in phosphatidylethanolamine.
When a cell undergoes programed cell death (apatosis) this phospholipid is present on the outer leaflet
phosphatidylserine
Different cells have different ____composition
phospholipid --> The phospholipid composition of red blood cells is different from that of myelin cells. Bacteria E. coli do not have phosphatidylcholine but are rich in phosphatidylethanolamine and phosphatidylglycerol
Intracellular membranes in the same cell have ___ lipid composition
different (distinct)
The distinct lipid composition of intracellular membranes is achieved through ...
directional intracellular trafficking of lipids from the site of synthesis to a final destination (i.e. cholesterol is made in peroxisome/ER but is transported to plasma membrane, where it is a main constituent)
These specialized lipid "microdomains" on the same plane of biomembrane are not homogenously distributed
lipid rafts
Lipid raft
rich in cholesterol and sphingolipids (e.g. sphingomyelin) and a unique group of proteins assoiated with raft involves cell signal transduction
the Kennedy pathway
The glycerophospholipids biosynthesis; pathway for phosphatidylcholine and phosphatidylethanolamine biosynthesis
PE and PC synthesis in the Kennedy pathway share these common features:
three reactions are involved: (i) activation of the head groups catalyzed by kinase, (ii) formation of CDP-containing intermediates, and (iii) transfer of phosphorylated head groups to DAG.
Activation of Choline and Ethanolamine in Kennedy Pathway (step 1) is catalyzed by which enzymes?
choline kinase and ethanolamine kinase; REQUIRES ATP
What is the difference b/w ethanolamine and choline?
Choline has three methyl groups attached to amine group, whereas ethanolamine is just the amine groups
Formation of CDP-ethanolamine and CDP-choline (step 2) is catalyzed by which enzyme?
Requires CTP: phosphoethanolamine cytidylyltransferase
In step 3 of the Kennedy pathway, the transfer of P-ethanolamine or P-choline to DAG is catalyzed by which enzyme?
CDP-ethanolamine:diacylglycerol phosphoethanolamine transferase
The Kennedy pathways for PC and PE synthesis intersect with the de novo TAG synthesis pathway at which intermediate?
DAG, which is the precursor for PC, PE and TAG synthesis
What is the PE methylation pathway ?
pathway through which the ethanolamine group is successively methylated to become CHOLINE(occurs in the liver)
The methyl group donor for the three consecutive methylation reactions is:
S-adenosylmethionine (SAM)
In mammals, this enzyme catalyzes all three three steps in the PE methylation pathway:
PE methyltransferase (PEMT)--> highly expressed in LIVER
the two intermediates of the PE methylation pathways are?
PMME (phosphatidylmonomethylethanolamine) and PDME (phosphatidyldimethylethanolamine)
What are the two pathways used to synthesize PC?
In the liver, PC is synthesized by the CDP-choline pathway (the Kennedy pathway) and PE methylation pathway (70% and 30%, respectively)--> NOTE: these pathways are DISTINCT, do not share similar functions
The base-exchange pathway is used for synthesis of
Phosphotidylserine
Phosphatidylserine synthesis in mammalian cells is achieved by ____ the head group of phosphatidylcholine or phosphatidylethanolamine with serine
swapping
Base exchange reaction is catalyzed by
PS synthase-1 and PS synthase-2 [The PS synthase-1 catalyzed base-exchange reaction using phosphatidylcholine as a substrate]
Enzymes involved in PC synthesis are located in the _____
endoplasmic reticulum [PEMT involved in PE methylation, CPT (CDP-choline:diacylglycerol phosphocholine transferase) form Kennedy pathway, and reactions reside in ER as an integral membrane protein]
Rate limiting step in Kennedy pathway
cytidylyltransferase catalyzed CDP-choline formation [Formation of CDP-choline is catalyzed by CTP:phosphocholine cytidylyltransferase (CT), which is activated by translocation from cytosol to ER membranes]
Soluble substrates in PC synthesis
CDP-choline, CTP, and Phosphocholine (derived from soluble choline)
The activity of this enzyme is regulated by its translocation b/w cytosol and ER membranes
CT (cytidylyltransferase): cytosolic form is inactive, whereas the membrane-bound CT is active
the major glycerophospholipids in mammalian cells are
PC and PE
de novo synthesis of PC and PE is achieved via
the Kennedy pathways
liver contains the _____ pathway to synthesize PC
PE methylation
DAG is an important intermediate that acts as a link between
phospholipid and TAG synthesis
What is the common feature of spingosine
sphingosine backbone= fatty acid side chains with a double bond
Sphingosine is building block for making a ____ (rich in brain and nervous system)
ceramide (acyl chain= C16:0 or C18:0)
Structure: Sphingosine is synthesized from condensation of
palmitoyl-CoA (palmitic acid) and serine
Explain the Biosynthesis of sphinganine
serine and palmitoyl-CoA condense to form Ketosphinganine. This is catalyzed by SPT (serine palmitoyltransferase),an integral membrane protein located in the ER. Ketosphinganine is subsequently converted to sphinganine, catalyzed by the NADPH-dependent KS
synthesis of N-acyl derivatives of sphinganine
sphinganine is acylated to form dihydroceramide (also called N-acylsphinganine), a reaction catalyzed by ceramide synthase (CerS). The mammalian CerS1 is highly selective for stearoyl-CoA and formation of C18-(dihydro)Cer. CerS is located in the ER.
desaturation of dihydroceramide
The last step in ceramide synthesis is the desaturation of dihydroceramide to introduce 4,5-trans-double bond (characteristic of ceramine). The enzyme catalyzing this reaction is dihydroceramide desaturase (DES). DES is an ER enzyme. The enzyme requires F
Ceramide is a precursor for which two synthesis
sphingomyelin and sphingoglycolipid
How is sphingomyelin synthesized?
Sphingomyelin is synthesized by transferring phosphocholine from phosphatidylcholine to ceramide by SMS (sphingomyelin synthase)This reaction liberates DAG. The SMS is an integral membrane protein located in the Golgi apparatus. Thus, ceramide must be tra
_____ are the simplest sphingoglycolipids that contain one sugar moiety of either glucose (GlcCer) or galactose (GalCer).
Cerebrosides
The enzymes catalyzing cerebroside synthesis are...
UDP-Glc: ceramide glycosyltransferase (CGlcT) and UDP-Gal: ceramide glycosyltransferase (CGalT)
Where are the Cerebroside sugar moieties located
GlcCer is synthesized on the cytosolic side of the ER and Golgi apparatus, and GalCer is synthesized in the lumen of the endoplasmic reticulum
_____ is the only sphingophospholipid that is synthesized in the Golgi apparatus
sphingomyelin
globosides and gangliosides are complex sphingoglycolipids that are synthesized in the ___ and are eventually presented on the cell surface
Golgi lumen [requires flippase enzyme to transport GluCer from cytosolic side to lumen of ER where it is transported to Golgi]