4th Unit / Ch 17 Complex Lipid Metabolism Flashcards
Phospholipid Structure 17 1.1
To what carbon backbone are the FAs and polar head groups esterified in the PLs shown?
What name is given to this group of PLs? From what precursor are they derived?
The FAs and polar headgroups are esterifi ed to a
glycerol backbone and are the glycerophospholipids.
Glycerophospholipids are derived from PA (DAG-P).
[ Note: PA is common to glycerophospholipid and TAG
synthesis.]
Phospholipid Structure 17 1.2
What are ether PLs?
Ether PLs (e.g., phosphatidalethanolamine, a
plasmalogen ) have the FA attached to C-1 of the
glycerol backbone by an ether link and not an ester
link.
[ Note: Platelet-activating factor is also an ether
PL. It binds to membrane receptors and triggers potent
thrombogenic and inflammatory events.]
Phospholipid Structure 17 1.3
What are sphingophospholipids?
Sphingophospholipids (e.g., sphingomyelin of nerve
myelin sheaths) are PLs that contain the amino alcohol
sphingosine as the backbone and not glycerol.
Phospholipid Structure 17 1.4
The Wassermann test for syphilis detects Abs against cardiolipin. Why would these Abs
be formed?
Cardiolipin (a glycerophospholipid) is virtually exclusive
to the inner mitochondrial membrane in eukaryotes,
where it stabilizes the ETC complexes. With active
syphilis , damage to infected cells exposes antigenic
cardiolipin. Additionally, Abs are formed against cardiolipin
found in the plasma membrane of the organism
( Treponema pallidum ) that causes syphilis.
Phospholipid Synthesis and Degradation 17 2.1
In the synthesis of glycerophospholipids from phosphatidic acid PA, as shown, either CDP-activated diacylglycerol (DAG) or a CDP-activated alcohol is required.
Which is used in the synthesis of Phospholipids (PI)? Of phosphatidylcholine PC?
CDP-DAG is used for Phospholipids (PI) synthesis and CDP-choline for phosphatidylcholine PC synthesis.
[ Note: Synthesis of most Phospholipids (PLs) occurs in the
- *Sarcastic Endoplastic Reticumlum.** However, cardiolipin is made in mitochondria and
- *plasmalogens** in peroxisomes.
Phospholipid Synthesis and Degradation 17 2.2
By what other process can phosphatidylcholine PC be made in the liver?
phosphatidylcholine (PC) (also known as lecithin ) can be made in the liver by decarboxylation of Phosphatidylserine (PS) to Phosphatidylethanolamine PE, which gets methylated
to phosphatidylcholine PC using S-adenosylmethionine SAM as the methyl group donor. The liver has a high requirement for phosphatidylcholine PC because it (1) secretes it
into bile to solubilize cholesterol and (2) uses it in VLDL
synthesis.
Phospholipid Synthesis and Degradation 17 2.3
What role does PLA 2 play in PhosphoLipid degradation?
PLA2 (A2 shown) cleaves the FA (typically unsaturated)
from C-2 of a PhosphoLipid. It plays a role in dietary PhosphoLipid digestion
and in the release of arachidonic acid from membrane PhosphoIipid.
Phospholipid Synthesis and Degradation 17 2.4
What is the cause of Niemann-Pick disease (types A and B)?
Niemann-Pick disease (types A and B) is a
lysosomal storage disease caused by a deficiency of
sphingomyelinase that normally hydrolyzes phosphorylcholine
from sphingomyelin, generating ceramide.
Type A is more severe than B.
Functions of Phospholipids 17 3.1
What second messengers are produced from PIP 2 , shown outlined by a red box in the cell membrane?
IP3 and DAG are the second messengers produced from PIP2 by Phospholipase C PLC, activated when a hormone binds a
Gq-type GPCR.
Functions of Phospholipids 17 3.2
What structure tethers some proteins to membrane-bound PI on the extracellular surface of cells?
A GPI anchor , in which a protein is covalently attached through a carbohydrate bridge to membrane-bound PI, tethers some proteins (e.g., ALP ) to the
extracellular surface.
Functions of Phospholipids 17 3.3
What is the clinical signifi cance of an L (lecithin) to S (sphingomyelin) ratio of < 2 in amniotic fluid?
Lung maturity results from the shift in synthesis from S to L, specifi cally dipalmitoylphosphatidylcholine ( DPPC ), in type II pneumocytes at -32 weeks of gestation.
DPPC is the major lipid component of surfactant that decreases surface tension, thereby reducing the pressure needed to inflate alveoli during inspiration. An L to S ratio < 2 elicits concern for respiratory distress.
Glycosphingolipids 17 4.1
What molecule is the immediate precursor of the glycosphingolipids and sphingomyelin (a sphingophospholipid), as shown?
Ceramide (sphingosine with a FA in an amide link) is the immediate precursor of the glycosphingolipids and sphingomyelin.
[Note: Ceramides help maintain skin’s water- permeability barrier.]
Glycosphingolipids 17 4.2
How do glycosphingolipids and sphingophospholipids differ structurally?
Glycosphingolipids do not contain phosphate, and the polar head group is provided by one or more sugars attached to ceramide. Cerebrosides contain one sugar, and globosides contain more than one. Acidic glycosphingolipids also contain NANA or sulfate (from PAPS ).
[Note: Glycosphingolipids are abundant in nerve tissue and
are located in the extracellular face of the cell membrane, thus allowing interaction with the extracellular environment. They are antigenic and also can serve as receptors for cholera and tetanus toxins.]
Glycosphingolipids 17 4.3
What is the result of B-hexosaminidase A (alpha subunit)
deficiency?
Deficiency in the alpha subunit of B-hexosaminidase A causes ganglioside G M2 accumulation and results in Tay-Sachs disease ,one of several sphingolipidoses caused by
_lysosomal sphingolipid acid hydrolase deficienc_y (shown).
Eicosanoids 17 5.1
What 20-carbon, polyunsaturated, w-6 FA serves as
the precursor for the synthesis of the predominate
series of Prostaglandins PGs, Thromboxanes TXs, and Leukotrienes LTs (collectively known as the eicosanoids), as shown?
The eicosatetraenoic FA, arachidonic acid, is the precursor of the predominant series of eicosanoids.
Eicosanoids 17 5.3
Why would a deficiency of linoleic acid, an essential
w-6 FA, decrease the synthesis of the eicosanoids?
Because humans cannot insert double bonds after C-10 in a FA, we are unable to synthesize arachidonic acid de novo.
However, we are able to elongate and desaturate dietary linoleic acid, 18:2(9,12), to arachidonic acid. Therefore,
linoleic acid deficiency would decrease availability of the precursor for eicosanoid synthesis.
[ Note: Arachidonic acid is incorporated into membrane PLs (primarily PI) at C-2 until it is released by PLA 2 .
Cortisol inhibits PLA 2 activity.]
Eicosanoids 17 6.1
Which isozyme, COX-1 or COX-2 shown, is inducible (nonconstitutive)?
COX-2 is inducible in a limited number of tissues. Induction results in the synthesis of PGs that mediate the pain, heat, redness and swelling of inflammation,
and the fever of infection. COX-1 , constitutively expressed in most tissues, maintains healthy gastric tissue and modulates renal function and platelet aggregation.
Eicosanoids 17 6.2
How do the NSAIDs (including aspirin) affect the activity of COX? Of LOX?
NSAIDs (including aspirin) inhibit both COX isozymes. Aspirin, but not other NSAIDs, causes irreversible inhibition by covalent acetylation. Aspirin does not inhibit LOX and may even favor use of arachidonic acid by LOX for synthesis of the LTs, mediators of bronchoconstriction.
[Note: Cortisol indirectly inhibits both COX and LOX by directly inhibiting PLA 2 and the release of arachidonic acid, their substrate.]
Eicosanoids 17 6.3
Why might inhibitors specifi c for COX-2 be associated with increased risk of an MI ?
COX-2 synthesizes PGI 2 ( prostacyclin ) that decreases platelet aggregation and vasoconstriction. Its specifi c inhibition would increase the risk of clotting (e.g., in a cardiac vessel in an MI ).
[ Note: COX-1 synthesizes TXA 2 that increases platelet aggregation and vasoconstriction. COX-1 inhibition causes
decreased clotting, the most common side effect of aspirin use.]
