complex lipids

what are the 4 major groups of molecules found in cells

nucleic acid, proteins, polysaccharides, lipids

what are the different types of lipids

fatty acids and TAG, glycerophospholipids, sphingolipids, steroids, other lipids

out of the different types of lipids what are complex lipids

glycerophospholipids and sphingolipids

lipid definition

lipids are substances of biological origin that are soluble in organic solvents such as chloroform and methanol

glycerophospholipids is structuraly related with

triglycerides

triglyceride is

the glycerol linked with 3 fatty acid chains

glycerophospholipids has a

glycerol backbone and 2 fatty acids, but 3rd link is phospho-alcohol group

glycerophospholipids has _________head group and ____________fatty acid tails

hydrophilic, hydrophobic

PC

phosphatidylcholine

PE

phosphatidylethanolamine

PS

phosphatidylserine

PI

phosphatidylinositol

PG

phosphatidylglycerol

hydrophilic head group can be

alcohol + phosphate

what alcohol groups can be in hydrophilic head group

PC, PE, PS, PI, PG

hydrophobic tail consist of

glycerol and fatty acid

glycerophospholipid =

phosphatidyl + alcohol

a special glycerophospholipid known as cardiolipid structure consist of

2 phosphatidyl groups that share glycerol head group

what is required for efficient electron transfer between complex 3 and 4 in respiration chain in inner mitochondria membrane

cardiolipin

what is a major type of phospholipid in mitochondria enriched in nerve and muscle tissue, heart and brain

plasmalogen

what accounts for 20% of total phospholipids in humans

plasmalogens

precursors of de novo synthesis of glycerophospholipdis

G3P (from lipolysis) and DHAP (from glycolysis)

what are both G3P and DHAP converted into in de novo synthesis

lysophosphatidic acid then phosphatidic acid

what is added to phosphatiidc acid in order to synthesize phospholipids

hydrophilic head groups (has 2 routes for adding)

2 routes for adding hydrophilic head groups to phosphatidic acid (PA)

PC/PE synthesis, PG/DPG/PI/PS synthesis

PC/PE synthesis (1st step)

PA converted to DAG

PC/PE synthesis (2nd step)

choline/ethanolamine converted to CDP-choline/CDP-ethanolamine

PC/PE synthesis (3rd step)

DAG react with CDP-choline/CDP-ethanolamine to form PC/PE

PG/DPG/PI/PS synthesis

PA converted to CDP-DAG

in PC synthesis what occurs to the choline head group

its converted to phosphocoline then activated to CDP-choline by a pyrophosphorylase reactioni

in PC synthesis what happesn to pyrophosphate bond

its cleaved and phosphocoline is transderred to DAG to form PC

in PE synthesis what is used to form CDP-ethanolamine

CTP and phosphoethanolamine

for PG synthesis PA is

activated to CDP-DAG by pyrophosphorylase reaction, pyrophosphate bond is cleaved the PA transfers to glycerol to form PG

biosynthesis is done by

de novo synthesis, remodeling pathway (exchange head group, acyl transfer)

remodeling by exchange of head groups

large amount of PC needed in liver for biosynthesis of lipoproteins and bile in liver

in a secondary pathway PC can be formed by

methylation of PE with methyl donor SAM

methylation of PE (supplied from PS) involve

sequential transfer of 3 activated methyl group from 3 molecule of SAM

land cycle (remodeling pathway)

acyl chain composition of major mammal phospholipid PC is distinct in various tissues

phospholipids remodeled by action of

PLA2 and LPLAT

PC acyl chain remodeling

PLA2 remove fatty acyl group from sn2 to produce lysoPC, then replaced by fatty acyl group by LPCAT uzing fatty acyl coa as donor, cycle continue to let composition of phospholipid to be remodeled for different cellular functions

DPPC is a type of _____ that can be enriched/used in the ______

PC, lungs

glycerophospholipid metabolized by

phospholipases

types of phospholipases

PLA1/2, PLB, PLC, PLD

PLA1/2

release fatty acid chains, PLA1 - cleaved at sn1, PL2 - cleaved at sn2,

is sn1 or sn2 cleavage usually an unstaurated fatty acid chain (like arachidonic acid)

sn2

PLB

has both PLA1/2 activity, cleave acyl chain from sn1 and sn2 position of phospholipid, acts on lysoPC

PLC

release phosphorylated head groups via hydrolysis, involve in cell signal by cleave PIP2 to DAG + IP3, hydrolyze PC into DAG + phosphocholine

PLD

release head groups like choline, ethanolamine, serine, inositol, glycerol

ex. PC cleaved into PA and choline

PLA1 cleave at ____ PLA2 cleave at _____

sn1, sn2 (unsaturated fatty acid chain)

summary of PC synthesis and metabolism

PC de novo synthesis

interconversion between PC and PE/PS via head group remodel

PLA2 release fattty acid from PC; LPCAT mediate acyl chain remodel

PLC act on PC to release phophocholine and make DAG

PLD act on PC to release choline and make PA

function consist of

membrane component, release secondary messenger, release fatty acid, membrane anchor

what are the 2 major types of glycerophospholipids in intracellular or plasma membranes, and account fro more than 50% of total phospholipid species in eukaryotic membranes

PE and PC

PI, PS, PA are ____ abundant compared to PE and PC

less

SM is a

sphingolipid enriched in lysosome and plasma membrane

activation of growth factor by ligand binding leads to several signal cascades like (1)

Ras GTPase activated → Raf MEK ERK signaling

activation of growth factor by ligand binding leads to several signal cascades like (2)

PLC activated → PLC hydrolyze PIP2 into IP3 + DAG → IP3 mediate Ca release from intracellular Ca stores + DAG activate PKC

activation of growth factor by ligand binding leads to several signal cascades like (3)

PI3K activated → PI3K phosphorylate PIP2 to PIP3 → PIP3 activate PKC

IP3 is a

secondary messenger that mobilize Ca from intracellualr Ca stores

IP3 released from

PIP2 by PLC

what is head group of PIP2

IP3

AA is released from

SN2 of membrane phospholipids by PLA2

steroids inhibit

phospholipases causing inhibition of arachidonic acid formation

AA is metabolized by COX into

PGI2 (vasodilation inhibit platelet aggregation) and TXA2 (vasoconstriction promote platelet aggregation)

AA is converted by LO/12-LO into

HETE and lipoxins

COX1 and COX2 inhibitors are

aspirin, which causes inhibition of pathway preventing PGI2 and TXA2 formation

GPI membrane anchors may be released from cell surface by

PLC in response to regulatory process

GPI used to

anchor surface proteins to cell

sphingolipids structure

fatty acid + r group + sphingosine

sphingomyelin has

ceramide (hydrophobic backbone) and phosphocholine (hydrophilix head)

3 types of sphinoglipids

ceramide, glycosphingolipids, phosphosphingolipids

simple sphinogolipid contains

sphingolipid without phosphate group(ceramide), phospho-sphingolipid (SM,S1P,C1P)

glycosphingolipids contain

ceramide + sugars (can be simple or complex sugars)

ceramide plays central role in

sphingolipid metabolism

ceramide can be de novo synthesized from

serin + palmitoyl coa

what is the only sphingolipid that is de novo synthesized

ceramide

gangliosides are

glycolipids containing NeuAC

NeuAC

predominant sialic acid found in human cells

ceramide can also be derived from

other sphingolipid like sphingomyelin hydrolysis by sphingomyelinase

fabry disease

GB3 degradation pathway, alpha-galactosidase deficiency, result in lysosomal accumulation of GB3

gaucher disease

deficieny b-glucosidase, accumulate GlcGer, result liver/spleen enlargement

tay-sachs disease

deficiency hexosaminidase a, accumulate GM2, result blind/mental retardation

krabbe disease

deficiency in b-galactosidase, accumulate LacGer, result liver/spleen enlargement

LSD (lysosomal storage disease)

result from defect in glycolipid degradation, accumulate precursor sphingolipids

function of sphingolipid

cell signal, bind site for bacteria and bacterial toxin, antigenic determinants

due to inter convertibility of sphingolipid biosyntehtic pathway molecules,

activity of single enzyme may affect fate of cell

S1P and C1P have opposite functions once

phosphorylated

S1P promotes

cell motility, survival, proliferation, inflammation

C1P promots

cell survival, profliferation, inflammation

another name for distinct membrane domains

lipid rafts

lipids rafts

50-100nm in size, enriched in sphingolipid and cholesterol rich, resistant to nonionic detergants, high affinity to certain proteins like GPI anchor proteins

cholera toxin released from _________ and _______________

bacteria in gut lumen, bind by B subunit to GM1 receptors on enterocytes triggering endocytosis of A subunit

bacterial sigella toxin bind to

GB3

bacterial tetanus toxin bind to

GT1B

cholera toxin goes to activate G proteins causing

activationf of adenylyl cyclase and increase cAMP which activate membrane bound CFTR protein causing efflux of Cl, Na, and water from intestinal epithelium

ABO GlcNac blood antigen

N-acetylglucosamine

ABO GalNac blood antigen

N-acetylgalatactosamine

type O

only H substance, universal donor but develop Abs against A and B

type A

H and A, develop Ab against B

type B

H and B, develop Ab against A

type AB

H,A, B, universal recipients