11 - Phospholipid Metabolism Flashcards
What is the most abundant type of phospholipid? What is the other main type?
Glycerophospholipids, they are components of membranes. They have esters between the glycerol and fatty acid chains.
Sphingolipids: have a sphingosine backbone with NO ESTER, a fatty acylated sphingosine is a ceramide.
Give a broad description for glycerophospholipid assembly
Synthesized from 3-carbon sugar phosphate by fatty acylation and addition of a nitrogen base
Describe bacterial glycerophospholipids
- Phospholipids only function as membrane components in bacteria
- Only phosphatidylethanolamine, phosphatidylglycerol and cadiolipin are present
In eukaryotes, phospholipids are much more complex in fatty acid side chains and headgroups
What are the only three fatty acids that can be conjugated to a phospholipid in prokaryotes?
- Palmitate (16:0)
- Palmitoleate (C16:1)
- cis-vaccenate (18:1cΔll)
Give steps of phosphatidylcholine in prokaryotes and mammals
Prokaryotes
- CDP-diacylglycerol is converted to phosphatidyl-serine by serine, releasing a CMP (the phosphate was transferred to the serine).
- Phosphatidyl serine is then decarboxylated to phosphatidyl-ethanolamine
- PE is then converted to phoatidylcholine by 3 adoMet, releasing 3 adoHcy
Mammals
- Choline to CDP-choline
- CDP-choline converted to phosphatidylcholine after reacting with diacylglycerol (CMP is released)
What are the three sources of phosphatidic acid in eukaryotes?
- Acyl chains are added to glycerol-3-phosphate (as acyl-CoA esters)
- CoA thioester acylation and reduction of dihydroxyacetone phosphate (DHAP). (abundant in adipose tissue because of glycolysis)
- Phosphorylation of diacylglycerol (DAG) generated during phospholipid turnover
What is the branch point between the synthesis of phospholipids and triacylglycerols?
Phosphatidic acid
Once you have phosphatidic acid, how is this converted to CDP-diacylglycerol?
- Metabolic activation by CTP (similar to polysaccharide synthesis activation by UTP)
- CTP is the cofactor for phospholipid biosynthesis and is required to activate the sn-3 position for addition of the headgroup - The reaction releases PPI through hydrolysis, which drives the reaction to completion.
- Headgroups are then attached to the sn-3 position with release of CMP
Describe the addition of headgroups to CDP-diacylglycerol on the road to becoming phospholipid.
- CMP on the CDP-DAG is replaced by either serine or glycerol phosphate alcohol to form phosphatidylserine (/ phosphatidylserine synthase) or phosphatidylglycerol-3-phosphate (PG3P) (/PG 3-phosphatase synthase)
Further modifications generate cardiolipin (/ cardiolipin synthase) and phosphatidylethanolamine (/ phosphatidylserine decarboxylase)
Why does phosphatidylserine not accumulate in bacteria?
It is decarboxylated to phosphatidylethanolamine via PS decarboxylase
Cardiolipin is synthesized by the condensation of what two molecules?
Two molecules of phosphatidylglycerol, which is formed by phosphohydrolysis of phosphatidic acid
At what level if phospholipid biosynthesis regulated in E.coli?
Fatty acid synthesis, because in this species, fatty acids are not used for energy sources, only for membranes.
Describe the addition of headgroups in eukaryotes
- The polar headgroup (base) is activated by CTP and then condensed with diacylglycerol
- An analogous pathway is used to synthesize phosphatidylethanolamine
What does methylation of phosphatidylethanolamine do? What other metabolic process may this be important for?
Converts the headgroup to choline
The reaction utilizes S-adenosylmethionine (AdoMet) as methyl group donor
May be very important in liver for the generation of phosphatidylcholine for lipoprotein synthesis
Describe the synthesis of phosphatidylinositol
- Phosphoinositides (PIPs) are important second messengers in membrane signalling pathways
- They are synthesized on demand and degraded rapidly
- Generated by phosphorylation of the hydroxyl groups of inositol
