Metabolism of Complex Lipids Flashcards
Lipids
-diverse and ubiquitous group of organic compounds that are insoluble in water, but soluble in organic solvents
General lipid classification
- glycerol based and none glycerol based
- glycerol backbone and non glycerol backbone
Glycerol based lipid classificaion
-simple and complex
None glycerol based lipids
- waxes
- steroids
- sphingolipids(amino and alcohol backbone)
- glycosphingolipids(major of this group in humans)
Simple glycerol based
- 3 fatty acids
- glycerol backbone
Compouns glycerol based
- phospholipids and glycolipids
- glycerol backbone
- 2 fatty acids
- 1 additional product(phospho group and polar group OR glucose)
Types of phospholipids
-glycerophospholipids and sphingophospholipids
Glycerophospholipids
- complex
- phospholipid
- 2 fatty acids at position 1 and 2
- glycerol backbone
Sphingophospholipds
- complex
- phospholipids
- Backbone: amino alcohol
- FA attached to backbone is bromitic acid
Sphingomeylin
- only sphingolipid that also has polar head group
- structural component of plasma membrane
Phospholipid structure
- amphipathic
- hydrophilic head: phosphate group and backbone
- Hydrophobic tail: fatty acids and hydrocarbons
- in water, they arrange so hydrophilic heads are out and hydrophobic tails are in to form a bilayer(formed spontaneously)
Three arrangements of lipid bilayers
- able to separate from other molecules so basically starting point for cells
- lipid bi-layer sheet
- lipid bi-layer sphere
- single layer lipid sphere
- depends on…
- type of phospholipids that are prensent
- the polar head groups
- the types of FA attacheded(length and saturation)
Phospholipid functions
- structural components
- reservoir for intracellular second messengers
- degradation of phospholipids release them - anchor for membrane proteins
- component for lipoprotein particles(chylomimcrons, VLDL)
- component for pulmonary surfactants(secrete epithelial cells)
- component for bile
Phospholipids and tears
- layer tear structure
- PC, PE and SM are major ones used
- thinning of this layer leads to evaporation of tears and dry eye
- decreased PL found in cataracts
Phosphatidic acid (PA)
- glycerophospholipid
- precursor for synthesis of other glycerophospholipids and TAG
- signaling molecule
- influence membrane curvature
- transfer vesicles from molecules
- simple!!!!
Phosphatidycholine (PC)
- lecithin
- PC=PA+Choline
- most abundant phospholipid
- storage for choline
- component of lung surfactant(DPPC)
- eggs
Lung Surfactant
- 90% lipids, 10% proteins
- decreases surface tension of extracellular fluid covering the alveoli
- reduces pressure needed to re-inflate alveoli
- prevents atelectasis(alveolar collapse)
- DPPC is most abundant phospholipid
Respiratory Distress Syndrome
- RSD
- infants
- insufficient lung surfactant
- lung surfactant is formed at 32 weeks, so premies dont have it.
- mom is given cholic acid before to help
Phosphatidylethanolamine(PE)
- PE=PA+ethanolamine
- second most abundant
- synthesis of phosphatidylserine in reaction with free serine
- nervous tissue
Phosphatidylserine(PS)
- PS=PA+Serine
- only found in inner leaflet of the plasma membrane
- required for membrane synthesis
- recognizes apoptotic cells
- when exposed in outermembrane, it shows that cell is dying an signals macrophages to clean it up
Phosphatidylinositols (Pls)
Pl=PA+inositol
- contains stearic acid at C1 and arachidonic acid at C2
- reservoir for arachidonic acid
- precursor for prostaglandins
- OH group can be phosphorylated to produce secondary messengers
- in retina cells for photoreception
Phosphatidylglycerol (PG)
- PG=PA+ glycerol
- recursor for surfactant
- presence in amniotic fluid indicated fetal lung maturity
- precursor for cardiolipin
Cardiolipin
- 2 PA molecules esterified through phosphate groups
- ONLY IN INNER MITOCHONDRIAL MEMBRANE
- MAINTAINS STRUCTURE AND FUNCTION OF ETC COMPLEXES
Ether glycerophospholipids
- FA at position 1 via ETHER linkage
- 2 types based on the saturation of FA at position 1
Plasmalogens
- ether glycerophospholipid
- unsaturated FA at position 1
Phosphatidalcholine
-plasmalogen in heart muscle
Phosphatidalethanolamine
-plasmalogen in nerve tissue
Platelet-aggregating factor (PAF)
- ether glycerophospholipid
- saturated FA at position 1
- short acetyl group at position 2 (NOT ACYL GROUP)
- synthesized and released by variety of cell types
- most potent bioactive molecule: triggers thrombotic and inflammatory events
- mediates anaphylaxis and hypersensitivity
Locations of glycerophospholipids
-always associated with the membrane and need a transporter to move
Most lipids: Smooth ER–>golgi(packaged/modified)–>transport vesicles–>other membranes
Ether lipids: peroxisomes
Synthesis of phosphatidic acid (PA)
- all cells EXCEPT mature erythrocytes can synthesize PA from…
- glycerol 3 phosphate
- 2 fatty acyl CoA
-any cells with ER can synthesize phospholipids
CDP-DAG pathway
-used for synthesis of PI,PG and cardiolipin
Transfer of activated CDP-choline or CDP-ethanolamine to DAG
- kennedy pathway
- synthesis of PC and PE
- choline and ethanolamine originate from diet and are primarily for liver
Synthesis of PS
- PE is used as a substrate
- base exchange reaction
- reversible step, but primarily only moves to produce PS
Synthesis of PC from PS and PE in the liver
- PS decarboxylated to form PE
- PE methylated in 3 steps using methyl donors
- liver requires secondary mechanism to produce PC even when free choline levels are low because…
- PC is secreted out of liver in bile
- PC are incorporated into lipoproteins and secreted
Phospholipase (PLP)
- hydrolyze phosphodiester bond of glycerophospholipids
- site specific cleavage(can only cleave at position 2)
- release bioactive molecules that act as secondary messengers(DAG,IP3)
- participate in remodeling pf phospholipids together with fatty acyl CoA transferases
Sphingolipids structure
- major component of brain and nervous tissues
- structural component of membranes and some bioactive lipids (DAG and secondary messengers)
- amino alcohol backbone
Sphingomyelin
Ceramide + phosphocholine(polar head group)
- most abundant sphingophospholipid in mammals
- abundant in nerve tissues and myelin sheath
- role in lipid raft formation
- signaling as a precursor for bioactive ceramide
Lipid raft
-clusters of lipids, cholesterol, and sphingomyelin used for cell signaling
Ceramimdes
- sphingosine+fatty acid
- diverse group that differ in the type of FA attached to sphingosine
- precursor for SM and all glycosphingolipids
- bioactive second messener
- maintain skin’s water-permeability barrier
Sphingosine
palmitic acid+ serine
- bioactive second messenger
- precursor for sphingosine 1P
- no FA, just backbone
Sphingosine 1P
- bioactive second messenger recognized by GPCR
- controls endocytosis of rhodopsin and eye proteins and TRP channel
Glycosphingolipids in human cells
- play role in cellular interactions and growth and development
- transformed cells (cancer) change their plasma membrane glycosphingolipid composition
Antigenic
- carbohydrate portion of a glycolipid is the antigenic determinant
- source of blood group antigens
- function as antigens in embryonic development
- tumor antigens
- serve as cell surface receptors for toxins
Neutral GSLs
- cerebrosides
- ceramide+sugar
- galactosylceramide, glucosylceramide, lactosylceramide
- essential component of membranes(mostly on outer leaflet)
- lipid raft formation
- mostly in brain and peripheral tissues
Acidic GSL
- gangliosides
- CER+oligosaccharode+NANA
- found in ganglion cells in CNS
- negatively charged at pH 7
- lipid storage diseases lead to accumulation of these lipids
Sulfatides
- Acidic
- galactocerebroside+SO3 group
- found in kidney and brain
Sphingolipid synthesis step 1
- begins in ER with condensation of palmitoyl CoA and L-serine
- uses serine palmitoyl transferase
- rate limiting step
- needs PLP as coenzyme
Sphingolipid synthesis middle
- several steps to form sphingoid backbone and produce ceramide
- ceramide is transferred to Golgi and used as synthesis of sphingomyelin and glycosphingolipids
- from golgi to distributed to membranes by vesicular transport OR into lipoproteins in liver and gut
Sphingolipid degradation
-local degradation of SM in PLASMA MEMBRANE by neutral sphingomyelinases to produce ceramide
Complete degradation of SM and GSL
- internalized via endocytotic pathways in the LYSOSOMES by acidic enzymes with optimal pH of 4.5
- and deficiencies in ANY enzymes results in sphingolipidoses
Healthy state
-sphingolipid synthesis and degradation are balanced tightly so that compounds are at constant levels
Sphingolipidoses
- if particular acid hydrolase is defective, SL substrate accumulates
- disorders are progressive and mainly in nervous systems
- autosomal recessive
- genetic variability
- incident of sphingoipidoses is low in most populations
