Complex Lipids II Flashcards
What are the categories of glycerolipids?
1) triacylglycerols
2) glycerophopsholipids
3) ether glycerolipids
What complex lipid is a major component of a plasma membrane?
phospholipids (sphingolipids are also components of the plasma membrane)
What is the difference in structure between a glycerophospholipid and an ether glycerolipid?
glyercophosplolipids have a glycerol backbone with two attached fatty acids at positions 1 and 2 connected by ester bonds and an activated head group attached to the glycerol backbone by a phosphate
ether glycerolipids have an ether bond (instead of an ester bond) on the 1 position with a long chain ‘alcohol- (the alcohol is the same as the long chain hydrocarbon that makes the fatty acyl but without the C=O bond) attached to the glycerol backbone, a single fatty acid in the 2 position, and an activated head group attached to the glycerol backbone by a phosphate
What are the categories of sphingolipids?
sphingophospholipids and glycolipids
What is a structure similarity between glycerolipids, phospholipids, and sphingolipids?
they all have at least one fatty acid and almost all (except triacylglycerol) have an activated head group)
What kinds of glycerophospholipids are primarily found on the cytosolic side of the plasma membrane?
phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylinositol bisphosphate (PI)
What kinds of complex lipids are primarily found on the extracellular part of the plasma membrane?
sphingomyelin, phosphatidylcholine, and glycolipids
What are the types of ether glycerolipids?
plasmalogens and platelet activating factor (PAF)
Where are plasmalogens commonly found?
mitochondria lipids, myelin, and muscle
What is platelet activating factor?
signaling molecule released from phagocytic blood cells in response to stimuli; causes platelet aggregation, edema, and hypotension
How is the ethanolamine plasmalogen “phosphotidylethanolamine” synthesized?
start with DHAP, which reacts with an activated fatty acyl CoA to give an ester group on the 1 carbon. Another fatty acyl CoA becomes reduced by 2 NADPH to a fatty acyl alcohol. Reaction of the fatty acyl alcohol and the product of the interaction between DHAP and the activated fatty acyl CoA displaces the ester bond on the 1 position, forming an ether bond. The 2 carbon is reduced to form an alcohol for the addition of a fatty acid and the 3 carbon is dephosphorylated. An activated CDP-ethanolamine head group reacts with the 3 carbon to form the head. Further oxidation modifies the 1 carbon to its final, unsaturated (1-alkenyl double bond) form
What are the main structural differences between phosphotidylethanolamine (plasmalogen) and PAF?
phosphotidylethanolamine - the 2 carbon has an acyl group and the 1 carbon ether chain is unsaturated
PAF- the 2 carbon has an acteyl group, the 1 carbon ether chain is saturated, and the head group is choline
What are the major categories of sphingolipids?
sphingophospholipids and glycolipids
What are the subsets of sphingophospholipids?
sphingomyelin- a major component of cell membranes
What are the subsets of glycolipids?
Cerebrosides
Sulfatides
Globosides
Gangliosides
(name depends on the sugar/carbohydrate moiety stuck on the 3 carbon of the sphingosine backbone)
What is the backbone of the sphingolipids made of?
a sphingosine molecule
A sphingosine joined together with a fatty acid by an amide bond is called what?
a ceramide
What do sphingolipids primarily do?
they are in the outer part of the plasma membrane and are involved in the cell-cell (e.g. ABO blood type), and cell-matrix interactions.
Sphingomyelin is enriched in CNS and in the myelin sheath
What families of complex lipids have a sphingosine backbone?
sphingophospholipids and glycolipids (aka the sphingolipids)
What is the difference between the structure of glycolipids and sphingophospholipids?
both have sphingosine backbones- makes an L shape- (where the 2 carbon fatty acid is attached to the sphingosine backbone by an amide bond, not an ester bond) but glycolipids have a phosphorylated choline on the 3 carbon and sphingophospholipids have a carbohydrate on the 3 carbon
How is the ceramide backbone of sphingophospholipids and glycolipids made?
1) start with palmitoyl CoA (16C fatty acyl CoA)
2) palmitoyl CoA reacts with serine in a enzymatic reaction that requires paradoxyl-phosphate (PLP) (and releases Co2 and CoA) forming a sphingosine
3) sphingosine is reduced to dihydrospingosine by NADPH
4) dihydrospingosine has a fatty acyl CoA added to a nitrogen on the serine residue
5) oxdiation by FAD (goes to FAD(2H)) adds a double bond on the backbone
glycolipids and sphingophospholipids are especially enriched where?
in neural tissue
What is mucolipidosis?
an inability to degrade sphingolipids and glycolipids (have CNS related symptoms)
ex. Tay-Each’s disease, Gaucher’s disease
To make sphingomyelin (subset of sphingophospholipids) from a ceramide backbone, what is needed? Where is sphingomyelin found?
a phosphotiydylcholine (PC) molecule to donate its activated choline residue to the 3 carbon
enriched in myelin sheath
Where are glycolipids especially abundant?
neural tissue
What do glycolipids primarily do?
cell-cell recognition, protect cells, and form the binding sites for some toxins (like choleratoxin)
T or F. glycolipids are ceramide derivatives
T. But they contain sugars, not activated choline and phosphate like in sphingophospholipids
What are cerebrosides composed of on the 3 carbon?
a single sugar attachment to the the ceramide backbone (e.g. ceramide bound to glucose makes glucocerebroside)
What are globosides composed of on the 3 carbon?
multiple sugar attachements on the ceramide backbone.
What are the neural glycolipid categories?
cerebrosides and globosides
What are the acidic glycolipid categories?
sulfatides and gangliosides (negatively charged at phsyiological pH)
contain an N- acetylneuraminic acid (NANA) (gangliosides) or sulfate (sulfatides) attached to the sugar moiety of a neutral glycolipid
Where does synthesis of glycolipids occur?
in the ER and in golgi
The sulfate for sulfatides is donated by what?
phosphoadenosine phosphosulfate (PAPS)
How is galactocerebroside formed?
addition of an activated galactose (aka UDP-galactose) to the ceramide backbone
How is sulfatide formed?
addition of a sulfate group from PAPS to galactocerebroside
How is glucocerebroside formed?
addition of an activated glucose (aka UDP-glcuose) to the ceramide backbone
How is globoside formed?
addition of a galactose group to a glucocerebroside by an appropriate enzyme
How is ganglioside formed?
addition of UDP-activated sugars to glucocerebroside, followed by addition of CMP- NANA (makes GM3).
What are sphingolipids (sphingphospholipids and glycolipids) degraded by?
lysosomal enzymes
What is Gaucher Disease?
B-glucocerebroside deficiency causing accummulation
autosomal-recessive
What is Tay-Sach Disease?
hexoaminidaside A deficiency/absent causing GM2 ganglionoside accummulation
autosomal recessive
CNS problems, seizures, muscle weakness,
What is Fabry Disease?
deficiency of a-galactosidase A causing accumulation of globosides
autsomal recessive
