Lipids Flashcards by teri miller

what are lipids?

hydrophobic molecules include;
phospholipids
glycophospholipids, isoprenoids, eicosenoids

all come from Acetyl CoA

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Phospholipids

major comp of cell membranes

glycerophospholipids (glycerol backbone)
sphingolipids (ceramide)

alcohol attached via phosphodiester bond to DAG (diaclyglycerol)

can be sat / unsat
diff head groups

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cardiolipin

unusual glycerophospholipid:
two phosphatidic acids eterified to an additional glycerol molecule

found only in inner mito mem (part of ETC0

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plsmalogens

glycerophospholipid;
fatty acid at C1 of glycerol is attached via an ether linkage (rather than ester)

most common plsamalogens:
phsphatidalenthanolamine & phsphatidalcholine
30% of glycerphospholipids in brain
reduced levels ~ Alzheimer’s disease

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platelet activating factor

ether glycerophospholipid
fatty acid chain on C2 replaced by an acetyl group

platelet aggregation and degranulation, inflammation, analphylaxis

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trans vs cis double bond

trans wont put a kink in the fatty acid tail

nature of tails affects fluidity of membrane

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C1 generally saturated tail

C2 unsaturated tail

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sphingophospholipids

long chain amino alcohol sphingosine as backbone

sphingomyelin is major sphingosine

choline head group
myelin sheath

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glycerophospholipids are derived from

phosphatidic acid

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what is phosphatidic acid synth from?

2 fatty acyl tails + glycerol-3-phosphate (from DHAP)

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formation of phosphatidylcholine (PC)

deP Phosphatidic acid -> DAG + CDP-Choline
Methlylation of PE ->PC
- PC has 3 methyl grps
- SAM - S-adenosyl-methionine (methly donor) req 3
Phosphatidylserine -> PC
- decarboxylational; phosphatidylserine DC (PLP)
- or base transfer; phosphatidyl-ethanolamine-serine transferase

Choline; diet or lipid turnover

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phosphatidlethanolamine (PE)

deP Phosphatidic acid -> DAG + CDP-ethanolamine

Ethanolamine; diet or lipid turnover

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Phosphatidyl inositol (PI)

DAG is activated by UDP

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Phosphatiditylserine (PS)

base exchange between serine and PE

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sphingolipid synthesis

palmitoyl CoA + Serine
enz; serine palmitoyl transferase
req NADPH
Spinganine (1 tail) - > Dihydroceramide
enz; Ceramid synthase
Dihydroceramide -> Ceramide (2 tail)
ceramide sphingomyelin
-transfer of the choline fr PC
-> enz: sphingomyelin synthase
<- enz: sphingomyelinase (SMase)

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phospholipase

degrade glycerophospholipids by hydrolize phosphodiester bonds
activate 2nd messengers

-release 1 tail = lysophospholipid (good detergent - alter solubility)
- acyl chains released = intermediates;
PL-A2 -> arachidonic acid -> syn of prostaglandins, leukotriees, thromboxanes

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Phospholipase C

PL -C; act by Gprotein coupled receptors, alpha-adrenergic R acts on PIP2 -> DAG + IP3
IP3 -> Ca release
DAG -> act PK-C (also act by Ca)

NE or EP
Constriction of blood vessels - sm mm

Phospholipase A 2

release hydrocarbon tail at 2nd C -> the unsat FA

PL - A2 alpha - specific for those with arachidonic acid
-> generation of prostaglandins, leukotrienes, etc

sphingomyelinase

degrade sphingophospholipids
remove phosphorylcholine = > ceramide
(ceramide further degraded into sphiingosine and free FA)

SMase classified by pH optima

Niemann-Pick disease

lysosomal acid SMase

Neimann-Pick (A,B) disease, AR
lipid buildup in cells
A - more severe, neuro defects, death early
ashkenazi jews
B - 5% fuction, lipid dep in liver
C & D - transporter problem -> build up of lipids inside cells

glycosphingolipids

derived from ceramide (like sphingolipids)
No phosphoester moiety
Polar portion = monosaccharide or oligos attached via O-glycosidic linkage
classified as neutral or acid

neutral glycosphingolipids

neutral charge
single sugar (glucose or galactose = glucocerebroside/galactocebroside) or oligosaccharide (globoside)

most common found in mem = galactocerbroside

glucocerbrosides = precursors of more complex glycosphingolipids

acidic glycosphingolipids

neg at phys pH due to:
1. N-acetyleneuraminic acid (NANA aka silaic acid) (note: attached via CMP-NANA)
= gangliosides - ganglion cells of CNS
2. Sulfate = sulfatides

gangliosides

acidic glycosphingolipids w NANA attached

Gm - 1 NANA, cholera toxin interacts here
Gd - 2
Gt - 3
Gq - 4

carb portion stick out from cell surface; communication, bacteria use them as receptor for toxins

sulfatides

cerebrosides containing sulfated galatosyl residues sulfate donor; (PAPS) 3 phosphoadenosine 5 - phosphosulfate attached to 3 OH of galactose

where are glycosphingolipids synthesized and how

golgi sequential attachment of UDP-sugars by glycosyl transferases to the glucose (similar to glycogen syn)

degradation of glycosphingolipids: where how

endocytosed into lysosomes lysosomal hydrolases - remove sugars 1 at a time -> ceramide ceramide -> sphingosine + FA normal; balance bet syn & deg = constant amt of glycosphingolipids in membrane 1 hydrolase deficient / absent -> buildup of glycosphingolipids in lysosomes

lipidoses

buildup of glycosphingolipids in lysosome due to deficiency/absence of a lysosomal hydrolase

Tay-sachs

lipidoses defect; hexosaminidase A -> buildup of Gm2 (gangliosides) rapid, progressive, fatal neurodegen blindness, cherry red macula, mm weakness, seizures

Gaucher disease

Gaucher diesease = enz beta-glucosidase (aka glucocerbrosidase) -> buildup of glucocerbrosides most common lysosomal storage disease hepatospienomegaly osteoporosis of long bones CNS inovl in rare infantile/ juvenile forms

eiconsinoids

include: prostaglandins, thromboxanes, leakotrienes PG/TX - platelet agg, ovulation, gastric acid sec, gastric mucous formation, vasocon/relax LK - allergic response, asthma, netrophil & eosinophil function, airway dia all derived from 20C omega-6 FA - most cases = arachidonic acid - der from linoleic acid, released from mem phospholipids via PL A 2

Prostaglandins and thromboxanes synethesis

PGH synthase (2 catalytic act); takes Arachadonic acid: 1. fatty acid cyclooxygenase (COX) - forms the intermediate PGG2 req O2 2. Peroxidase - converts PGG2 -> PGH2 req glutathione PGH2 -> converted to a number of diff things dep on cell type (aka the enzymes present)

COX 1

const expressed in all tissue

COX 2

inc induced cytokines/ inflammatory response

COX inhibitors

NSAIDS - non-selective COX inhib ant-inflammatory (blocks COX-2) side-affects; stomach upset bc of COX 1 inhibition (dec mucous sec)

selective COX-2 inhib

celecoxib only COX assoc w anti-inflam response should have no side-effects may have adverse cardiovascular effects -> unpredicted side effects

TXA 2

platalet agg

PGI 2

inhibits platelet aggregation | endothelial cells

how do prostaglandins/thromboxanes exert their effects?

via specific G-protein coupled receptors (GCPRs) in target cells PGI 2 - syn by endothelial cells, ihibits platelet aggregation TXA2 - syn by platelets and triggers aggregation Result = limit platelet aggregation to site of injury

aspirin

COX - 1 irreversible (fround in platelets) COX - 2 reversible Platelets - anucleated so can't produce more proteins, so shuts doesn platelet TXA2 production and aggregation low-dose aspirin therapy more or less platelet specific

leukotriene synthesis

enz; 5-lipoxygenase (5-LOX); arachadoinc acid -> leukotriene A4 (LTA4) (intermmediate = 5-hydroperoxyeicosatetranoic acid, 5 HPETE) not Cyclic (unlike prostaglandins and thromboxanes) exert effects via GPCR many contain conj cysteine residue (fr glutathione) = Cysteinyl leukotrienes - these are the slow-reacting substance of anaphylaxis (SRS-A) - asthma - inhib of 5-LOX & antagonists of CysLT-1 tx for asthma